lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=c1[nH]c(SCc2ccc(-c3ccc(S(=O)(=O)NC4COC4)c(F)c3)cc2F)nc2c1CCC2
InChIKey: UTXHYAKNKVDRIH-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of recombinant human MMP13 using APMA and fTHP-15(FAM) as substrate preincubated for 30 mins followed by substrate addition by fluorescence microplate reader assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 505.57, ALogP 3.17, HBA 6, HBD 2, PSA 101.15, QED 0.38
Compound (SMILES): N#Cc1c(N)nc(N)nc1N1CC2(CC2)C[C@H]1c1nc(NCc2ccc(C(=O)NO)cc2)c2c(Cl)cccc2n1
InChIKey: KFSLDNTVFDBWLH-IBGZPJMESA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) measured by fluorescence based assay
Measurement: IC50 = 398 nM (pChEMBL 6.400000095367432)
Descriptors: MW 557.02, ALogP 3.57, HBA 11, HBD 5, PSA 191.99, QED 0.17
Compound (SMILES): O=C1S/C(=C\c2c(NCCO)nc3ccccn3c2=O)C(=O)N1CCc1ccccc1
InChIKey: OXZUOKIKLKZCBD-VKAVYKQESA-N
Target: ATP-dependent RNA helicase DDX3X (SINGLE PROTEIN), Homo sapiens
UniProt: O00571
Assay: Binding affinity to DDX3X (unknown origin) assessed as inhibition constant
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 436.49, ALogP 2.38, HBA 8, HBD 2, PSA 104.01, QED 0.55
Compound (SMILES): O=C1NC(=S)NC(=O)C1=Cc1cc(-c2cc(Cl)c(O)c(Cl)c2)ccc1OCc1ccccc1
InChIKey: IELWXSVQTPMCEM-UHFFFAOYSA-N
Target: Phosphotyrosine-protein phosphatase PTPB (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P96830
Assay: Inhibition of recombinant Mycobacterium tuberculosis H37Rv MptpB using pNPP as substrate incubated for 10 mins and measured by spectrophotometric method
Measurement: IC50 = 3810 nM (pChEMBL 5.420000076293945)
Descriptors: MW 499.38, ALogP 4.86, HBA 5, HBD 3, PSA 87.66, QED 0.27
Compound (SMILES): O=C(Nc1ccc2[nH]ncc2c1)[C@H]1CCCN1C(=O)C1(c2cccc(Cl)c2)CCCC1
InChIKey: QYWHBBPDNLLPPX-OAQYLSRUSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Inhibition of full-length P300 (unknown origin) using ARTKQTARKSTGGKAPRKQLAGG-K(Biotin)-amide as substrate preincubated for 60 mins followed by substrate addition and measured by RapdiFire-MS/MS analysis
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 436.94, ALogP 4.66, HBA 3, HBD 2, PSA 78.09, QED 0.62
Compound (SMILES): COc1ccc(Cl)cc1NC(=O)CN1CCN(S(=O)(=O)N2CCN(S(=O)(=O)c3ccccc3)CC2)CC1
InChIKey: DQQCPXBQYCDKEF-UHFFFAOYSA-N
Target: Potassium channel subfamily T member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5JUK3
Assay: Inhibition of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 572.11, ALogP 1.16, HBA 7, HBD 1, PSA 119.57, QED 0.5
Compound (SMILES): Cc1noc(C)c1C(=O)Nc1nnc(C2CC2)s1
InChIKey: OXBPDHNXDPMVNB-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 (unknown origin) expressed in Escherichia coli BL21 (DE3) using [Lys(Ac)5/8/12/16]-histone H4 (1 to 21residues)-GGK as substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 86000 nM (pChEMBL 4.070000171661377)
Descriptors: MW 264.31, ALogP 2.27, HBA 6, HBD 1, PSA 80.91, QED 0.92
Compound (SMILES): Cc1c(C(N)=O)c[n+]([O-])c2c1CCN2
InChIKey: QHAKQQCWDPZCDX-UHFFFAOYSA-N
Target: Nicotinamide N-methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P40261
Assay: Inhibition of human NNMT measured after 20 mins by luminescence based methyltransferase assay
Measurement: IC50 = 7055 nM (pChEMBL 5.150000095367432)
Descriptors: MW 193.21, ALogP -0.3, HBA 3, HBD 2, PSA 82.06, QED 0.47
Compound (SMILES): O=C(c1ccc2nc(-c3ccccc3)c(-c3ccccc3)nc2c1)N1CCOCC1
InChIKey: XMOAXXRVOGXRCI-UHFFFAOYSA-N
Target: 15-hydroxyprostaglandin dehydrogenase [NAD(+)] (SINGLE PROTEIN), Homo sapiens
UniProt: P15428
Assay: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins
Measurement: IC50 > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 395.46, ALogP 4.44, HBA 4, HBD 0, PSA 55.32, QED 0.51
Compound (SMILES): CCN(CC)Nc1nc(N/N=C/c2ccccc2O)nc(Nc2ccccc2)n1
InChIKey: SXMXTPMUWSXQGV-KGENOOAVSA-N
Target: ATP-dependent RNA helicase DDX3X (SINGLE PROTEIN), Homo sapiens
UniProt: O00571
Assay: Binding affinity to DDX3X (unknown origin) assessed as inhibition constant
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 392.47, ALogP 3.44, HBA 9, HBD 4, PSA 110.59, QED 0.32
Compound (SMILES): Cn1cc(Cc2ccccc2OCCN2CC3(COC3)C2)c(-c2cc(Cl)nc(N)n2)n1
InChIKey: UCAQZKORNBZGSL-UHFFFAOYSA-N
Target: Adenylate cyclase type 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PN6
Assay: Inhibition of human ADCY10 assessed as cAMP accumulation preincubated for 15 mins followed by substrate addition using alpha-32P labelled ATP as substrate by sequential chromatographic analysis
Measurement: IC50 = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 440.94, ALogP 2.41, HBA 8, HBD 1, PSA 91.32, QED 0.56
Compound (SMILES): CC(C)=CCC/C(C)=C/OC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCCN
InChIKey: FRDLQTNCWFXSNK-YERQVDBCSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of DPP4 (unknown origin) using Gly-Pro-AMC as substrate incubated for 30 mins by fluorescence based enzyme immunoassay
Measurement: IC50 = 15.3 nM (pChEMBL 7.820000171661377)
Descriptors: MW 365.52, ALogP 2.63, HBA 5, HBD 2, PSA 98.65, QED 0.27
Compound (SMILES): O=c1[nH]c2ccc(OCc3cccc(I)c3)cc2c(=O)o1
InChIKey: VDSJKFQALTXWHD-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant MAO-A assessed as inhibition of 4-hydroxyquinoline formation using kynuramine as substrate incubated for 20 mins by fluorescence spectrophotometry
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 395.15, ALogP 2.66, HBA 4, HBD 1, PSA 72.3, QED 0.69
Compound (SMILES): O=C(c1ccc2ncc(-c3ccc4[nH]c(=O)ccc4c3)nc2c1)N1CCCCC1
InChIKey: DXRKWWKXZPCXTL-UHFFFAOYSA-N
Target: 15-hydroxyprostaglandin dehydrogenase [NAD(+)] (SINGLE PROTEIN), Homo sapiens
UniProt: P15428
Assay: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins
Measurement: IC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 384.44, ALogP 3.76, HBA 4, HBD 1, PSA 78.95, QED 0.57
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC1CC1)CC2)c1ncc(-c2cc3ccc(C4CC4)nc3cc2OC)[nH]1
InChIKey: DWSUDVIZAAHXQY-VEEOACQBSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human HDAC1 using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 < 0.3 nM (pChEMBL 9.52299976348877)
Descriptors: MW 611.83, ALogP 7.11, HBA 6, HBD 2, PSA 100.21, QED 0.18
Compound (SMILES): C[C@]1(c2nc(-c3cccc(N)c3)no2)CCCc2sc(N)c(C#N)c21
InChIKey: INMTVGHSNGHSIG-SFHVURJKSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Binding affinity to KRAS G12V mutant (unknown origin) assessed as dissociation constant by HSQC NMR spectroscopy analysis
Measurement: Kd < 10000 nM (pChEMBL 5)
Descriptors: MW 351.44, ALogP 3.48, HBA 7, HBD 2, PSA 114.75, QED 0.68
Compound (SMILES): COc1ccc(-c2cnc3c(N4CCOCC4)ncnc3c2)cc1OC
InChIKey: VZOPCTJZOFIUIQ-UHFFFAOYSA-N
Target: Cyclin-G-associated kinase (SINGLE PROTEIN), Homo sapiens
UniProt: O14976
Assay: Binding affinity to GAK (unknown origin) by KINOMEscan analysis
Measurement: Kd = 7300 nM (pChEMBL 5.139999866485596)
Descriptors: MW 352.39, ALogP 2.55, HBA 7, HBD 0, PSA 69.6, QED 0.71
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](C2CCCCC2)NC(=O)[C@H](CC(=O)O)NC(=O)CNC1=O
InChIKey: JWLUUUDPTVFYQJ-ULMVMLMRSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Binding affinity to Integrin alphaVbeta3 (unknown origin)
Measurement: IC50 = 364 nM (pChEMBL 6.440000057220459)
Descriptors: MW 595.66, ALogP -3.36, HBA 8, HBD 10, PSA 287.79, QED 0.08
Compound (SMILES): NC(=O)c1nn(CC(=O)N2CCC[C@H]2C(=O)Nc2cccc(O)c2F)c2ccccc12
InChIKey: FOZFSZRJILVDPV-HNNXBMFYSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 425.42, ALogP 1.61, HBA 6, HBD 3, PSA 130.55, QED 0.57
Compound (SMILES): O=C(CS(=O)(=O)O)Nc1cc(Br)cc(Br)c1
InChIKey: DEWCKMZZBHNJJF-UHFFFAOYSA-N
Target: Low molecular weight phosphotyrosine protein phosphatase (SINGLE PROTEIN), Homo sapiens
UniProt: P24666
Assay: Inhibition of His-tagged human LMW-PTP expressed in Escherichia coli BL21 using pNPP as substrate incubated for 10 mins by microplate reader based spectrophotometric analysis
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 373.02, ALogP 2.04, HBA 3, HBD 2, PSA 83.47, QED 0.79
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2c[nH]c3ncccc23)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@@H]2CSCCC(=O)N3CN(CN(C3)C(=O)CCSC[C@@H](NC(C)=O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](Cc3ccccn3)C(=O)NCC(=O)N2)C(=O)CCSC[C@@H](C(=O)O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: FJFKJFQOQISUGU-YNMKYOMQSA-N
Target: Nectin-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96NY8
Assay: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay
Measurement: Ki > 9000 nM (pChEMBL 5.046000003814697)
Descriptors: MW 2151.56
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(CNCCCc2c[nH]c3ccc(F)cc23)CC1
InChIKey: GHTQLAJAELADED-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Inhibition of serotonin transporter in rat brain tissue assessed as inhibition of [3H]-5-hydroxytryptamine reuptake
Measurement: IC50 = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 445.94, ALogP 5.17, HBA 2, HBD 2, PSA 48.13, QED 0.49
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)Cc1c[nH]cn1)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)C(=O)N[C@@H](C)C(N)=O
InChIKey: UQCBGQFSEYRTGZ-VXVPDZCVSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R expressed in HEK293 cells incubated for 30 mins and assessed as increase in cAMP accumulation measured by HTRF assay
Measurement: EC50 = 0.62 nM (pChEMBL 9.210000038146973)
Descriptors: MW 4469.94
Compound (SMILES): CC(=O)Nc1ccc(/C=N/Nc2nc(Nc3ccccc3)nc(Nc3ccccc3)n2)cc1
InChIKey: YFUYPNOVLVHURP-PCLIKHOPSA-N
Target: ATP-dependent RNA helicase DDX3X (SINGLE PROTEIN), Homo sapiens
UniProt: O00571
Assay: Binding affinity to DDX3X (unknown origin) assessed as inhibition constant
Measurement: Ki = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 438.5, ALogP 4.76, HBA 8, HBD 4, PSA 116.22, QED 0.23
Compound (SMILES): CN(CCCOc1ccc2ccc(=O)oc2c1)Cc1cccc(OC(=O)NC2CCCCC2)c1
InChIKey: RIBSWIDLITYLHS-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human serum AChE using acetylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition measured for 45 to 90 mins by Ellman's method
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 464.56, ALogP 5.12, HBA 6, HBD 1, PSA 81.01, QED 0.35
Compound (SMILES): CC(C)(C)OC(=O)N1CCC(CNc2cc(Br)cc3[nH]ncc23)C1
InChIKey: ADRBSRRQNUNQLV-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 (12 to 403 aa) expressed in Escherichia coli Transetta (DE3) by nanodrop 2000c spectrophotometric analysis
Measurement: IC50 = 9020 nM (pChEMBL 5.039999961853027)
Descriptors: MW 395.3, ALogP 3.99, HBA 4, HBD 2, PSA 70.25, QED 0.82
Compound (SMILES): CC(C)C[C@H](NC(=O)OCC12CC3CC(CC(O)(C3)C1)C2)C(=O)N[C@H](C=O)C[C@H]1CCNC1=O
InChIKey: HCMUAXJAEVVGND-WUYKWXONSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 3CLpro using FAM-SAVLQ/SG-QXL520 as substrate measured after 1 hr by fluorescence based microplate reader analysis
Measurement: IC50 = 820 nM (pChEMBL 6.090000152587891)
Descriptors: MW 477.6, ALogP 1.67, HBA 6, HBD 4, PSA 133.83, QED 0.35
Compound (SMILES): CC(C)n1cc(S(=O)(=O)NC(=O)Nc2c3c(cc4c2CCC4)CCC3)cn1
InChIKey: FZMOHJPMOVXUFL-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 inflammasome activation in LPS and nigericin-stimulated human PBMC cells assessed as reduction in IL-1beta release preincubated with LPS for 3 hrs followed by compound addition for 30 mins and further stimulated with nigericin for 1.5 hrs by ELISA analysis
Measurement: IC50 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 388.49, ALogP 2.95, HBA 5, HBD 2, PSA 93.09, QED 0.84
Compound (SMILES): CCOC(=O)C1=C(O)C(=O)N(c2nc3ccc(C)cc3s2)C1c1ccc(OC)c2ccccc12
InChIKey: VNPWKZSVQMXKMQ-UHFFFAOYSA-N
Target: UDP-N-acetylglucosamine 1-carboxyvinyltransferase (SINGLE PROTEIN), Escherichia coli K-12
UniProt: P0A749
Assay: Inhibition of wild type his tagged Escherichia coli K12 MurA using UDP-N-acetylglucosamine as substrate preincubated with substrate for 30 mins prior to compound addition for 15 mins followed by DTT and PEP addition and measured after 30 mins by malachite green based microplate reader analysis
Measurement: IC50 = 9500 nM (pChEMBL 5.019999980926514)
Descriptors: MW 474.54, ALogP 5.23, HBA 7, HBD 1, PSA 88.96, QED 0.4
Compound (SMILES): C[C@@H](Oc1cc(NC(=O)c2cn(CCN3CCOCC3)c3cc(Br)c(C=O)nc23)ncc1C#N)c1c(Cl)cncc1Cl
InChIKey: CGZXQBNAWSMHFF-MRXNPFEDSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of N-terminal 6His-tagged FGFR4 (unknown origin) using Tyr04 peptide as substrate incubated for 1 hr in presence of ATP by FRET based Z'-LYTE assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 673.36, ALogP 5.3, HBA 10, HBD 1, PSA 135.26, QED 0.23
Compound (SMILES): CSCC1(C)CN(c2ccc3oc(N)nc3c2)c2c(N)ncnc21
InChIKey: YZESSOQLEODPGP-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibitory Activity on mTOR Kinase: The model for screening the inhibitory activity of the molecules on mTOR was developed with the LANTHASCREEN technology (Lifetechnologies). The reaction substrate (400 nM final), the serial dilutions of the molecules (1% DMSO final) and the enzyme (<1 nM) are successively added to a 384-well plate (Corning 4514) in a final volume of 10 μL per well. After 1 hour of reaction at room temperature, 10 μL of a solution containing 10 mM final of EDTA and 2 nM final of terbium-labeled antibodies are added. After at least 30 minutes of incubation at room temperature, the TR-FRET signal is measured with a suitable microplate reader according to the supplier's recommendations. The data are normalized with positive controls (POS containing a saturating concentration of reference inhibitor) and negative controls (NEG containing 1% DMSO): % inhibition=((X−NEG)*100)/(POS−NEG). The IC50 values are calculated using a 4-parameter logistic model with the aid of the XLFit software (IDBS)
Measurement: Ki = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 342.43, ALogP 2.55, HBA 8, HBD 2, PSA 107.09, QED 0.75
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)Cc1c[nH]cn1)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(N)=O
InChIKey: ATUXKYHTVPFXPN-PCFFOIMISA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R expressed in HEK293 cells incubated for 30 mins and assessed as increase in cAMP accumulation measured by HTRF assay
Measurement: EC50 = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 3584.96
Compound (SMILES): CC1CCN(S(=O)(=O)N2CCN(CC(=O)Nc3cccc(F)c3)CC2)CC1
InChIKey: KADCMHIWKRVQBD-UHFFFAOYSA-N
Target: Potassium channel subfamily T member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5JUK3
Assay: Activation of wild-type human Slack expressed in HEK293 cells measured by thallium flux assay
Measurement: EC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 398.5, ALogP 1.36, HBA 4, HBD 1, PSA 72.96, QED 0.81
Compound (SMILES): CCOC(=O)C1=C(O)C(=O)N(c2nc3ccc(C(F)(F)F)cc3s2)C1c1ccc(-c2ccccc2)cc1
InChIKey: KFUFYNSQVBTXNX-UHFFFAOYSA-N
Target: UDP-N-acetylglucosamine 1-carboxyvinyltransferase (SINGLE PROTEIN), Escherichia coli K-12
UniProt: P0A749
Assay: Inhibition of wild type his tagged Escherichia coli K12 MurA using UDP-N-acetylglucosamine as substrate preincubated with substrate for 30 mins prior to compound addition for 15 mins followed by DTT and PEP addition and measured after 30 mins by malachite green based microplate reader analysis
Measurement: IC50 = 6100 nM (pChEMBL 5.210000038146973)
Descriptors: MW 524.52, ALogP 6.45, HBA 6, HBD 1, PSA 79.73, QED 0.3
Compound (SMILES): Cc1c(O[C@@H]2O[C@H](CO[C@@H]3OC[C@@H](O)[C@H](O)[C@H]3O)[C@@H](O)[C@H](O)[C@H]2O)cc2c(c1O)C(=O)c1ccc(O)c(O)c1C2=O
InChIKey: FATNCJZCOOPLKZ-YJWXBJJPSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin)
Measurement: IC50 = 78000 nM (pChEMBL 4.110000133514404)
Descriptors: MW 580.5, ALogP -2.47, HBA 15, HBD 9, PSA 253.13, QED 0.14
Compound (SMILES): CCOC(=O)c1ccccc1C(=O)Nc1nnc(-c2ccc(OC)cc2)s1
InChIKey: GTVCURWVNYROAI-UHFFFAOYSA-N
Target: ATP-dependent RNA helicase DDX3X (SINGLE PROTEIN), Homo sapiens
UniProt: O00571
Assay: Binding affinity to His-tagged full-length recombinant human DDX3X expressed in Escherichia coli assessed as inhibition constant in presence of ATP by ADP-Glo kinase assay
Measurement: Ki = 20100 nM (pChEMBL 4.699999809265137)
Descriptors: MW 383.43, ALogP 3.64, HBA 7, HBD 1, PSA 90.41, QED 0.65
Compound (SMILES): O=c1[nH]c(SCc2ccc(-c3ccc(S(=O)(=O)N[C@H]4CCCC[C@@H]4O)cc3)cc2)nc2c1CCC2
InChIKey: CBVRSDFQRSNOJK-ZEQRLZLVSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of recombinant human MMP13 using APMA and fTHP-15(FAM) as substrate preincubated for 30 mins followed by substrate addition by fluorescence microplate reader assay
Measurement: IC50 = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 511.67, ALogP 3.8, HBA 6, HBD 3, PSA 112.15, QED 0.33
Compound (SMILES): O[C@H]1CCCC[C@@H]1CNc1cc(Br)cc2[nH]ncc12
InChIKey: KBSUKSFOQICUON-OTYXRUKQSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 (12 to 403 aa) expressed in Escherichia coli Transetta (DE3) by nanodrop 2000c spectrophotometric analysis
Measurement: IC50 = 2850 nM (pChEMBL 5.539999961853027)
Descriptors: MW 324.22, ALogP 3.29, HBA 3, HBD 3, PSA 60.94, QED 0.81
Compound (SMILES): Cc1ccc(C(=O)Nc2cc(-c3cnn(C)c3)cc(C3CC3)c2)cc1Nc1cc(-c2cccnc2)ccn1
InChIKey: WFHMWBUUXCZBDM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of full-length N-terminal His-tagged human c-Abl kinase (2 to 1130 residues) expressed in baculovirus expression system using Tk-substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 40 mins by HTRF assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 500.61, ALogP 6.73, HBA 6, HBD 2, PSA 84.73, QED 0.26
Compound (SMILES): CC(C)(C)OC(=O)N1CCN(C(=O)c2ccc3nc(-c4ccccc4)c(-c4ccccc4)nc3c2)CC1
InChIKey: JGPYRXOAOKFULJ-UHFFFAOYSA-N
Target: 15-hydroxyprostaglandin dehydrogenase [NAD(+)] (SINGLE PROTEIN), Homo sapiens
UniProt: P15428
Assay: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins
Measurement: IC50 > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 494.6, ALogP 5.66, HBA 5, HBD 0, PSA 75.63, QED 0.37
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@@H]2CSCCC(=O)N3CN(CN(C3)C(=O)CCSC[C@@H](NC(=O)[C@H](C)N)C(=O)N3CCC[C@H]3C(=O)N[C@@H](Cc3ccccc3)C(=O)NCC(=O)N2)C(=O)CCSC[C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: RJPGLRCZBQMRET-KLIJHDOQSA-N
Target: Nectin-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96NY8
Assay: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay
Measurement: Ki = 57.6 nM (pChEMBL 7.239999771118164)
Descriptors: MW 2249.7
Compound (SMILES): CO[C@H]1C[C@@H]2CC[C@@H](C)[C@@](O)(O2)C(=O)C(=O)N2CCCC[C@H]2C(=O)O[C@H]([C@H](C)C[C@@H]2CC[C@@H](OCCCN3CCOC(C)(C)C3)[C@H](OC)C2)C[C@@H](O)[C@H](C)/C=C(\C)[C@@H](O)[C@@H](OC)C(NOCC(=O)NCCOCCOCCOCCOCCOCCOCCC(=O)N2CCC(n3nc(-c4ccc5oc(N)nc5c4)c4c(N)ncnc43)CC2)[C@H](C)C[C@H](C)C/C=C\C=C\C=C\1C
InChIKey: PSBRTVBGCMNBIN-SAJNNVQISA-N
Target: mTORC1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BVC4
Assay: Inhibition of mTORC1 in human MDA-MB-468 cells assessed as measuring phosphorylated P70S6K incubated for 2 to 4 hrs by AlphaLISA assay
Measurement: IC50 <= 1 nM (pChEMBL 9)
Descriptors: MW 1828.31
Compound (SMILES): OCC(Nc1cc(Br)cc2[nH]ncc12)c1cccc(Cl)c1
InChIKey: GKPLJWJNVKPLDG-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 (12 to 403 aa) expressed in Escherichia coli Transetta (DE3) by nanodrop 2000c spectrophotometric analysis
Measurement: IC50 = 18330 nM (pChEMBL 4.739999771118164)
Descriptors: MW 366.65, ALogP 4.12, HBA 3, HBD 3, PSA 60.94, QED 0.65
Compound (SMILES): COCCNc1cc(NC(=O)c2cn(CCN3CCOCC3)c3ccc(C=O)nc23)ncc1C#N
InChIKey: LGNJEQYHWVYBAK-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of N-terminal 6His-tagged FGFR4 (unknown origin) using Tyr04 peptide as substrate incubated for 1 hr in presence of ATP by FRET based Z'-LYTE assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 477.53, ALogP 1.76, HBA 10, HBD 2, PSA 134.4, QED 0.33
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cc3ccc(C)nc3cc2F)o1
InChIKey: OTDRPXYPNVACGD-RSXGOPAZSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human HDAC1 using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 534.68, ALogP 6.16, HBA 6, HBD 1, PSA 88.33, QED 0.3
Compound (SMILES): [2H]C([2H])([2H])C(N[C@]([2H])(C)C(=O)c1cccc(Cl)c1)(C([2H])([2H])[2H])C([2H])([2H])[2H]
InChIKey: SNPPWIUOZRMYNY-JGVQANRZSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Inhibition of norepinephrine transporter (unknown origin) assessed as inhibition of norepinephrine reuptake
Measurement: IC50 = 6800 nM (pChEMBL 5.170000076293945)
Descriptors: MW 239.75, ALogP 3.3, HBA 2, HBD 1, PSA 29.1, QED 0.82
Compound (SMILES): Cn1cc(C(=O)Nc2cc(NCCN3CCOCC3)c(C#N)cn2)c2nc(C=O)ccc21
InChIKey: JYUIXLZWYDQBDP-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of N-terminal 6His-tagged FGFR4 (unknown origin) using Tyr04 peptide as substrate incubated for 1 hr in presence of ATP by FRET based Z'-LYTE assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 433.47, ALogP 1.65, HBA 9, HBD 2, PSA 125.17, QED 0.54
Compound (SMILES): Cc1cc(Cl)ccc1O[C@H](C)c1nnc(N)s1
InChIKey: ZZYXSDZGSTXXPQ-SSDOTTSWSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 (unknown origin) expressed in Escherichia coli BL21 (DE3) using [Lys(Ac)5/8/12/16]-histone H4 (1 to 21residues)-GGK as substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 79000 nM (pChEMBL 4.099999904632568)
Descriptors: MW 269.76, ALogP 3.22, HBA 5, HBD 1, PSA 61.03, QED 0.93
Compound (SMILES): O=C(CCN1C(=O)/C(=C/c2cccc(F)c2)SC1=S)Nc1ccccc1O
InChIKey: LMRVTFNRYQMTNZ-WJDWOHSUSA-N
Target: ATP-dependent RNA helicase DDX3X (SINGLE PROTEIN), Homo sapiens
UniProt: O00571
Assay: Binding affinity to DDX3X (unknown origin) assessed as inhibition constant
Measurement: Ki = 7600 nM (pChEMBL 5.119999885559082)
Descriptors: MW 402.47, ALogP 3.76, HBA 5, HBD 2, PSA 69.64, QED 0.45
Compound (SMILES): CCOC(=O)/C=C/OC(=O)[C@@H]1CCCN1C(=O)CNC(=O)OC(C)(C)C
InChIKey: WMMGQNJIXNJSMA-OANVXVOSSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of DPP4 (unknown origin) using Gly-Pro-AMC as substrate incubated for 30 mins by fluorescence based enzyme immunoassay
Measurement: IC50 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 370.4, ALogP 1.12, HBA 7, HBD 1, PSA 111.24, QED 0.32
Compound (SMILES): CCOC(=O)C1=C(O)C(=O)N(c2nc3ccc(Cl)cc3s2)C1c1ccc(-c2ccccc2)cc1
InChIKey: UORVPJCXAUFQSC-UHFFFAOYSA-N
Target: UDP-N-acetylglucosamine 1-carboxyvinyltransferase (SINGLE PROTEIN), Escherichia coli K-12
UniProt: P0A749
Assay: Inhibition of wild type his tagged Escherichia coli K12 MurA using UDP-N-acetylglucosamine as substrate preincubated with substrate for 30 mins prior to compound addition for 15 mins followed by DTT and PEP addition and measured after 30 mins by malachite green based microplate reader analysis
Measurement: IC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 490.97, ALogP 6.08, HBA 6, HBD 1, PSA 79.73, QED 0.34
Compound (SMILES): CC(C)(C)CN(Cc1ccc(Br)cc1)c1nccc(C#N)n1
InChIKey: UJFTZERUUFKJAO-UHFFFAOYSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of Cathepsin K (unknown origin) assessed as inhibition of AFC release using sequence LR labelled with AFC as substrate by fluorescence based analysis
Measurement: IC50 = 974.3 nM (pChEMBL 6.010000228881836)
Descriptors: MW 359.27, ALogP 4.16, HBA 4, HBD 0, PSA 52.81, QED 0.82
Compound (SMILES): COc1cc2c(cc1OC)[C@H](C)C(=O)N(C)CC2
InChIKey: PREGEFBQCOFCDI-VIFPVBQESA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 BD1 (unknown origin) measured by TR-FRET assay
Measurement: IC50 = 63095.73 nM (pChEMBL 4.199999809265137)
Descriptors: MW 249.31, ALogP 1.82, HBA 3, HBD 0, PSA 38.77, QED 0.8
Compound (SMILES): CCc1ccc2c(c1)C=CN(C)C(=O)[C@@H]2C
InChIKey: HKJSKLWZFAJKEW-SNVBAGLBSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 BD2 (unknown origin) measured by TR-FRET assay
Measurement: IC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 215.3, ALogP 2.8, HBA 1, HBD 0, PSA 20.31, QED 0.71
Compound (SMILES): O=C1NC(=S)S/C1=C\c1cnn(-c2ccccc2)c1
InChIKey: DZBOJHSPQXHPEC-WDZFZDKYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibitory Activity of mTORC1: Among the compounds of the Examples 1-1 to 1-61, compounds that showed excellent inhibitory activity (inhibitory activity of 85% or more at 20 μM) were selected to further evaluate the inhibitory activity of mTORC1. As a result, as shown in the Table 3, it was confirmed that each compound had an IC50 of 1 μM or less, and furthermore, it was confirmed that some compounds exhibited very excellent effects of an IC50 of 100 nM or less.
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 287.37, ALogP 2.36, HBA 5, HBD 1, PSA 46.92, QED 0.68
Compound (SMILES): Nc1ccc(Nc2ccc(O)c(C(=O)NCC(=O)O)n2)cc1
InChIKey: JCSJQUCGCIEKPQ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 6B (SINGLE PROTEIN), Homo sapiens
UniProt: O15054
Assay: Inhibition of human KDM6B preincubated for 15 mins followed by substrate addition and measured after 5 mins using H3(21-44)K27Me3-GK-biotin peptide as substrate by AlphaScreen-based assay
Measurement: IC50 = 89700 nM (pChEMBL 4.050000190734863)
Descriptors: MW 302.29, ALogP 0.93, HBA 6, HBD 5, PSA 137.57, QED 0.52
Compound (SMILES): Cn1c([C@@H]2C[C@@H](OCc3ccc(C(=O)NO)s3)CN2c2nc(N)nc(N)c2C#N)nc2cccc(Cl)c2c1=O
InChIKey: GCMCCGKCRIEJCC-BZNIZROVSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) measured by ADP-Glo assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 568.02, ALogP 2.13, HBA 13, HBD 4, PSA 198.3, QED 0.2
Compound (SMILES): CC(=O)O[C@@H]1CCCC[C@H]1CNc1cc(Br)cc2[nH]ncc12
InChIKey: UTABHBWYBVGRRE-MEDUHNTESA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 (12 to 403 aa) expressed in Escherichia coli Transetta (DE3) by nanodrop 2000c spectrophotometric analysis
Measurement: IC50 = 5780 nM (pChEMBL 5.239999771118164)
Descriptors: MW 366.26, ALogP 3.86, HBA 4, HBD 2, PSA 67.01, QED 0.81
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(N)(CCC3CC3)c3ccc(C(N)=O)nc3)ccc2F)c1
InChIKey: IQWHGFSUUIEJQU-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Plasma Kallikrein Activity Assay: The effect of compounds of the invention on human plasma kallikrein activity was determined using the chromogenic substrates (DiaPharma Group, Inc., West Chester, Ohio, USA). In these experiments, 2 nM kallikrein (Enzyme Research Laboratories, South Bend, Ind., USA) was incubated with 80 μM S2302 (H-D-Pro-Phe-Arg-p-nitroaniline) in the absence or presence of increasing concentrations of compounds of the invention in a final volume of 200 μL Tris-HCl buffer (200 mM NaCl; 2.5 mM CaCl2; 50 mM Tris-HCl, pH 7.8).After incubation at 30° C., the activity of kallikrein was measured as a change in absorbance at OD 405 nm using BioTek PowerWave X340 Microplate Reader (Winooski, Vt., USA). Data were analyzed using SigmaPlot software (Systat Software, Inc., San Jose, Calif., USA) (Four Parameter Logistic Curve). Ki values for the inhibitors were determined using the Cheng-Prusoff equation (Biochem. Pharmacol. 1973, 22, 3099).
Measurement: Ki = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 595.6, ALogP 4.63, HBA 7, HBD 4, PSA 154.94, QED 0.2
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(N)(CCC3CC3)c3ccncc3)ccc2F)c1
InChIKey: AGVFYPDLNPHKER-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Plasma Kallikrein Activity Assay: The effect of compounds of the invention on human plasma kallikrein activity was determined using the chromogenic substrates (DiaPharma Group, Inc., West Chester, Ohio, USA). In these experiments, 2 nM kallikrein (Enzyme Research Laboratories, South Bend, Ind., USA) was incubated with 80 μM S2302 (H-D-Pro-Phe-Arg-p-nitroaniline) in the absence or presence of increasing concentrations of compounds of the invention in a final volume of 200 μL Tris-HCl buffer (200 mM NaCl; 2.5 mM CaCl2; 50 mM Tris-HCl, pH 7.8).After incubation at 30° C., the activity of kallikrein was measured as a change in absorbance at OD 405 nm using BioTek PowerWave X340 Microplate Reader (Winooski, Vt., USA). Data were analyzed using SigmaPlot software (Systat Software, Inc., San Jose, Calif., USA) (Four Parameter Logistic Curve). Ki values for the inhibitors were determined using the Cheng-Prusoff equation (Biochem. Pharmacol. 1973, 22, 3099).
Measurement: Ki = 25.1 nM (pChEMBL 7.599999904632568)
Descriptors: MW 552.58, ALogP 5.53, HBA 6, HBD 3, PSA 111.85, QED 0.24
Compound (SMILES): Brc1cc(NCC2CCNC2)c2cn[nH]c2c1
InChIKey: GFPMRKDIWQPKPT-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO (19 to 388 aa) expressed in Escherichia coli Transetta (DE3) by nanodrop 2000c spectrophotometric analysis
Measurement: IC50 = 10440 nM (pChEMBL 4.980000019073486)
Descriptors: MW 295.18, ALogP 2.35, HBA 3, HBD 3, PSA 52.74, QED 0.81
Compound (SMILES): O=C(c1ccc2nc(-c3ccccc3)c(-c3ccccc3)nc2c1)N1CCC(CO)CC1
InChIKey: BFDXUTKDCVBJTE-UHFFFAOYSA-N
Target: 15-hydroxyprostaglandin dehydrogenase [NAD(+)] (SINGLE PROTEIN), Homo sapiens
UniProt: P15428
Assay: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins
Measurement: IC50 > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 423.52, ALogP 4.81, HBA 4, HBD 1, PSA 66.32, QED 0.51
Compound (SMILES): C/C(=N\NCCCN1C(=O)S/C(=C\c2ccc(OCc3ccccc3)cc2)C1=O)c1ccncc1
InChIKey: LELDJCNXAPGXMU-RMYUHZIOSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B
Measurement: IC50 = 12730 nM (pChEMBL 4.889999866485596)
Descriptors: MW 486.6, ALogP 5.1, HBA 7, HBD 1, PSA 83.89, QED 0.19
Compound (SMILES): COc1ccc(C2(C(=O)N3CCC[C@@H]3C(=O)Nc3ccc4[nH]ncc4n3)CCC2)cc1
InChIKey: CBHJIVVYJHGWTJ-LJQANCHMSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Inhibition of full-length P300 (unknown origin) using ARTKQTARKSTGGKAPRKQLAGG-K(Biotin)-amide as substrate preincubated for 60 mins followed by substrate addition and measured by RapdiFire-MS/MS analysis
Measurement: IC50 = 0.2512 nM (pChEMBL 9.600000381469727)
Descriptors: MW 419.49, ALogP 3.02, HBA 5, HBD 2, PSA 100.21, QED 0.66
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)[C@@H]2CSCCC(=O)N3CN(CN(C3)C(=O)CCSC[C@@H](NC(C)=O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](Cc3ccc4ccccc4c3)C(=O)N[C@H](CC(=O)O)C(=O)N2)C(=O)CCSC[C@@H](C(=O)O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: XYKMMJIUQWNSED-QLQAUNQJSA-N
Target: Nectin-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96NY8
Assay: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay
Measurement: Ki = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 2214.61
Compound (SMILES): CC(C)C[C@H](NC(=O)OCCC12CC3CC(CC(C3)C1)C2)C(=O)N[C@H](C=O)C[C@H]1CCNC1=O
InChIKey: YBRZKVAPDVWTRT-WOAYWDQESA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 3CLpro using FAM-SAVLQ/SG-QXL520 as substrate measured after 1 hr by fluorescence based microplate reader analysis
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 475.63, ALogP 2.94, HBA 5, HBD 3, PSA 113.6, QED 0.4
Compound (SMILES): Nc1noc2ccncc12
InChIKey: RBYICHYEXYRQFK-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Enzymatic Assay: Recombinant human IDO1 (rhIDO1) was expressed and purified from cultures of EC538 strain of E. coli transformed with pREP4 and pQE9-IDO plasmid. Reaction mixes were set up in 384-well microplates containing 50 mM phosphate buffer, 10 mM ascorbic, 10 μM methylene blue, 100 μg/mL catalase, 80 μM TRP, 0.01% Tween 20 (v/v) mixed with rhIDO1 (15 μL) at a final concentration of 9 nM in a total volume of 30 μL assay medium. The plates were incubated at 37° C. for 30 min, and the enzymatic reaction was terminated by adding piperidine (200 mM) and heated at 65° C. for 20 min. Fluorescence intensity was read at λex 400 nm and λem 500 nm. Test compounds were dissolved in 100% DMSO and pre-diluted in assay medium prior to adding rhIDO1.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 135.13, ALogP 0.8, HBA 4, HBD 1, PSA 64.94, QED 0.58
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc3ccc(=O)n(C)c3cc2OC)o1
InChIKey: UWIASJNPIIGSRX-FTJBHMTQSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human HDAC1 using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay
Measurement: IC50 = 0.49 nM (pChEMBL 9.3100004196167)
Descriptors: MW 576.74, ALogP 5.41, HBA 8, HBD 1, PSA 106.67, QED 0.27
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H]2NC(=O)[C@H](NC(=O)CN)CSSC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC(=O)O)NC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)c(I)c1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)CSSC2(C)C
InChIKey: PCZIHLUSNJIPJG-RJRAAHCASA-N
Target: Neuronal acetylcholine receptor; alpha9/alpha10 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9GZZ6
Assay: Inhibition of human alpha9alpha10 nAChR expressed in xenopus oocytes assessed as inhibition of Ach- induced response at -70 mV holding potential and measured for 1 to 5 days in presence of Ach stimulation by voltage-clamp based electrophysiological method
Measurement: IC50 = 0.39 nM (pChEMBL 9.40999984741211)
Descriptors: MW 1717.74
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@@H]2CSCCC(=O)N3CN(CN(C3)C(=O)CCSC[C@@H](NC(C)=O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](Cc3ccccn3)C(=O)NCC(=O)N2)C(=O)CCSC[C@@H](C(=O)O)NC(=O)[C@H](Cc2ccc3ccccc3c2)NC1=O
InChIKey: SCEHDQPAELRETH-INDKGIEWSA-N
Target: Nectin-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96NY8
Assay: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay
Measurement: Ki = 27.3 nM (pChEMBL 7.559999942779541)
Descriptors: MW 2161.59
Compound (SMILES): NC(=O)c1nn(CC(=O)N(CC(=O)NCc2cccc(Cl)c2F)C2CC2)c2ccc(NC(=O)N3CCN(C4CC4)CC3)cc12
InChIKey: ZHNLFMKNBJQZNY-UHFFFAOYSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition Assay: An established esterolytic assay for the measurement of Factor D activity and inhibition of Factor D activity was used (Kam, C. M.; McRae, B. J.; Harper, J. W.; Niemann, M. A.; Volanakis, J. E.; Powers, J. C. Human complement proteins D, C2, and B Active site mapping with peptide thioester substrates. J Biol. Chem. 1987, 262, 3444-3451). For this assay Z-Lys-SBzl, 1.29 mM (Kim, S.; Narayana, S. V. L; Volanakis, J. E. Mutational analysis of the substrate binding site of human complement Factor D. Biochemistry. 1994, 33, 14393-14399) was used as the substrate for Factor D (104 mM). Hydrolysis of this compound by Factor D liberated a free sulfhydryl group which is then reacted with 5,5′-dithiobis(2nitrobenzoic acid) producing an intense yellow color (Habeeb, A. F. S. A. Reaction of protein sulfhydryl groups with Ellman's Reagent. Methods in Enzymol. 1976, 25, 457-464.). The assays were performed in 96 well microtiter plates and rates of hydrolysis were monitored at 405 nm on a Biotek Synergy H1 plate reader. Hydrolysis rates were reported as change in mOD/min. The assay was conducted in 100 mM HEPES, 500 mM NaCl, pH 7.5 containing 10% DMSO in a final volume of 50 μL per well.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 625.1, ALogP 2.55, HBA 7, HBD 3, PSA 145.9, QED 0.32
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2c[nH]c3ccc(F)cc23)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)[C@@H]2CSCCC(=O)N3CN(CN(C3)C(=O)CCSC[C@@H](NC(C)=O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](Cc3ccccn3)C(=O)N[C@H](CC(=O)O)C(=O)N2)C(=O)CCSC[C@@H](C(=O)O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: JGTTYFDQPGMZKU-YHCKLZSLSA-N
Target: Nectin-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96NY8
Assay: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay
Measurement: Ki = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 2183.53
Compound (SMILES): CCOC(=O)C1=C(O)C(=O)N(c2nc3ccc(C)cc3s2)C1c1cc(-c2ccccc2)cs1
InChIKey: CVSVEEIKMHXGGN-UHFFFAOYSA-N
Target: UDP-N-acetylglucosamine 1-carboxyvinyltransferase (SINGLE PROTEIN), Escherichia coli K-12
UniProt: P0A749
Assay: Inhibition of wild type his tagged Escherichia coli K12 MurA using UDP-N-acetylglucosamine as substrate preincubated with substrate for 30 mins prior to compound addition for 15 mins followed by DTT and PEP addition and measured after 30 mins by malachite green based microplate reader analysis
Measurement: IC50 = 9900 nM (pChEMBL 5)
Descriptors: MW 476.58, ALogP 5.8, HBA 7, HBD 1, PSA 79.73, QED 0.37
Compound (SMILES): CCCn1cc(C(=O)Nc2cc(NCCOC)c(C#N)cn2)c2nc(C=O)ccc21
InChIKey: VENQMPULOCFARJ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of N-terminal 6His-tagged FGFR4 (unknown origin) using Tyr04 peptide as substrate incubated for 1 hr in presence of ATP by FRET based Z'-LYTE assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 406.45, ALogP 2.84, HBA 8, HBD 2, PSA 121.93, QED 0.41
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H]2NC(=O)[C@H](NC(=O)CN)CSSC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC(=O)O)NC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)c(I)c1)C(=O)N[C@@H](CCCN)C(=O)N[C@H](C(=O)N[C@H](CC(=O)N[C@@H](CCCN)C(=O)O)Cc1ccc(O)cc1)CSSC2(C)C
InChIKey: QHPSFIKTRMNNLZ-TZHKBYJCSA-N
Target: Neuronal acetylcholine receptor; alpha9/alpha10 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9GZZ6
Assay: Inhibition of human alpha9alpha10 nAChR expressed in xenopus oocytes assessed as inhibition of Ach- induced response at -70 mV holding potential and measured for 1 to 5 days in presence of Ach stimulation by voltage-clamp based electrophysiological method
Measurement: IC50 = 0.34 nM (pChEMBL 9.470000267028809)
Descriptors: MW 1831.93
Compound (SMILES): COc1ccc(OC)c(/C=C/C(=O)Nc2sc3c(c2C#N)CCC3)c1
InChIKey: UYIRUUKVNCDEGJ-RMKNXTFCSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of human TGF-beta-R1 using TMB substrate incubated for 2.5 hrs by microplate reader analysis
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 354.43, ALogP 3.78, HBA 5, HBD 1, PSA 71.35, QED 0.83
Compound (SMILES): O=C(c1ccc2ncc(-c3ccc(N4CCOCC4)nc3)nc2c1)N1CCCCC1
InChIKey: DRHGMMSIJNTDNR-UHFFFAOYSA-N
Target: 15-hydroxyprostaglandin dehydrogenase [NAD(+)] (SINGLE PROTEIN), Homo sapiens
UniProt: P15428
Assay: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 403.49, ALogP 3.15, HBA 6, HBD 0, PSA 71.45, QED 0.67
Compound (SMILES): CC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccc(Br)cc1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCNC(=S)Nc1ccc2c(c1)C(=O)OC21c2ccc(O)cc2Oc2cc(O)ccc21)C(N)=O)C(C)C
InChIKey: ASTGJZHWOAPURB-DJRMSAAUSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BQA1
Assay: Binding affinity to PRMT5/MEP50 (unknown origin) assessed as dissociation constant by FITC- Competitive binding assay
Measurement: Kd = 317 nM (pChEMBL 6.5)
Descriptors: MW 1600.48
Compound (SMILES): [2H]C([2H])(OC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@H]1CCNC1=O)C(O)S(=O)(=O)[O-])C12CC3CC(CC(C3)C1)C2.[Na+]
InChIKey: UYPRMIJZKBTNNB-SSEYHZIESA-M
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 3CLpro using FAM-SAVLQ/SG-QXL520 as substrate measured after 1 hr by fluorescence based microplate reader analysis
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 543.68, ALogP 1.56, HBA 7, HBD 5, PSA 171.13, QED 0.24
Compound (SMILES): CC(C)C[C@H](NC(=O)OCC1CC2C=CCC(C2)C1)C(=O)N[C@@H](C[C@H]1CCNC1=O)C(O)S(=O)(=O)[O-].[Na+]
InChIKey: OHUZLHDAXYGKCN-YERQUWECSA-M
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 3CLpro using FAM-SAVLQ/SG-QXL520 as substrate measured after 1 hr by fluorescence based microplate reader analysis
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 529.66, ALogP 1.34, HBA 7, HBD 5, PSA 171.13, QED 0.2
Compound (SMILES): COc1cc(NS(=O)(=O)c2ccc(OC)c(N3CCNCC3)c2)c(Cl)cc1Cl
InChIKey: BDWDLANQBRGPIP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [125I]cAMP-tracer from 5-HT6R in human HeLa cells assessed as measuring cAMP level incubated for 15 mins by radioimmunoassay
Measurement: Ki = 0.98 nM (pChEMBL 9.010000228881836)
Descriptors: MW 446.36, ALogP 3.22, HBA 6, HBD 2, PSA 79.9, QED 0.71
Compound (SMILES): COC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1
InChIKey: UKSHMMNPSXEPKW-PMACEKPBSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of DPP4 (unknown origin) using Gly-Pro-AMC as substrate incubated for 30 mins by fluorescence based enzyme immunoassay
Measurement: IC50 = 0.46 nM (pChEMBL 9.34000015258789)
Descriptors: MW 410.47, ALogP 2.69, HBA 5, HBD 1, PSA 84.94, QED 0.71
Compound (SMILES): Brc1cc(NC[C@@H]2CCCN2)c2cn[nH]c2c1
InChIKey: WSPZPKBHPTXVAJ-VIFPVBQESA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 (12 to 403 aa) expressed in Escherichia coli Transetta (DE3) by nanodrop 2000c spectrophotometric analysis
Measurement: IC50 = 4740 nM (pChEMBL 5.320000171661377)
Descriptors: MW 295.18, ALogP 2.49, HBA 3, HBD 3, PSA 52.74, QED 0.82
Compound (SMILES): O=C(O)c1ccccc1C(=O)Nc1nnc(-c2ccccc2[N+](=O)[O-])s1
InChIKey: CVRXPLNAIHCTIT-UHFFFAOYSA-N
Target: ATP-dependent RNA helicase DDX3X (SINGLE PROTEIN), Homo sapiens
UniProt: O00571
Assay: Binding affinity to His-tagged full-length recombinant human DDX3X expressed in Escherichia coli assessed as inhibition constant in presence of ATP by ADP-Glo kinase assay
Measurement: Ki = 18300 nM (pChEMBL 4.739999771118164)
Descriptors: MW 370.35, ALogP 3.06, HBA 7, HBD 2, PSA 135.32, QED 0.52
Compound (SMILES): Nc1ncc(-c2nc(N3CCOCC3)c3c(n2)N2CCOC[C@H]2C3)cn1
InChIKey: WLHXVOYGBREFJO-GFCCVEGCSA-N
Target: mTORC1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BVC4
Assay: Inhibition of mTORC1 (unknown origin)
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 355.4, ALogP 0.11, HBA 9, HBD 1, PSA 102.52, QED 0.8
Compound (SMILES): FC(F)(F)c1c(-c2ccc(OCC3CC3)c(Cl)c2)ccn2c(CC3CC3)nnc12
InChIKey: FTGLLUVESXGAPP-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Positive allosteric modulator activity at mGluR2 receptor (unknown origin) assessed as glutamate-induced [35S]GTPgammaS binding
Measurement: EC50 = 759 nM (pChEMBL 6.119999885559082)
Descriptors: MW 421.85, ALogP 5.81, HBA 4, HBD 0, PSA 39.42, QED 0.5