lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CO[C@@H]1C[C@@H]2CC[C@@H](C)[C@@](O)(O2)C(=O)C(=O)N2CCCC[C@H]2C(=O)OC([C@H](C)C[C@@H]2CC[C@@H](O)[C@H](OC)C2)CC(O)CC(=O)[C@H](C)/C=C(\C)[C@@H](O)CC(=O)[C@H](C)C[C@H](C)/C=C/C=C/C=C/1C
InChIKey: UHKOUPRMAKKTLW-XFTFGMQASA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP1A (SINGLE PROTEIN), Homo sapiens
UniProt: P62942
Assay: Binding affinity to FKBP12 (unknown origin) assessed as inhibition constant
Measurement: Ki = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 928.21, ALogP 6.31, HBA 13, HBD 4, PSA 206.43, QED 0.14
Compound (SMILES): Cc1cc(C(N)(CCC2CC2)c2ccc(F)c(NC(=O)c3cc(C(F)(F)F)nn3-c3cccc(CN)c3)c2)ccn1
InChIKey: PYONXWOUVYIBRU-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition of purified human plasma kallikrein using H-D-Pro-Phe-Arg-pNA.2HCl as substrate measured after 3 mins by microplate reader analysis
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 566.6, ALogP 5.84, HBA 6, HBD 3, PSA 111.85, QED 0.22
Compound (SMILES): COc1cc2c(cc1OC)C(=O)C(Cc1ccc(OC(=O)Nc3ccc(Cl)cc3)cc1)C2
InChIKey: WRFPARWDVKKXLR-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate incubated for 5 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 4640 nM (pChEMBL 5.329999923706055)
Descriptors: MW 451.91, ALogP 5.57, HBA 5, HBD 1, PSA 73.86, QED 0.53
Compound (SMILES): CC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H]1CCCCC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)O)C(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCC(N)=O)NC1=O)C(C)C
InChIKey: OYZWCBHNXUMCPU-XTDTXPIQSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BQA1
Assay: Binding affinity to PRMT5/MEP50 (unknown origin) assessed as inhibition constant by FITC- Competitive binding assay
Measurement: Ki = 313 nM (pChEMBL 6.5)
Descriptors: MW 1014.1
Compound (SMILES): CC(C)(C)OC(=O)NC1CCN(C(=O)c2ccc3nc(-c4ccccc4)c(-c4ccccc4)nc3c2)CC1
InChIKey: CUDOYDXPSJUABQ-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 508.62, ALogP 6.09, HBA 5, HBD 1, PSA 84.42, QED 0.36
Compound (SMILES): Cc1c(Br)cc(NC(=O)CS(=O)(=O)O)cc1Br
InChIKey: PGYFUNHIFMBZCB-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12923
Assay: Inhibition of FAP-1(unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 387.05, ALogP 2.35, HBA 3, HBD 2, PSA 83.47, QED 0.78
Compound (SMILES): Cc1c(Cl)c(=O)oc2cc(OCCCCSC(=S)N3CCCCC3C)ccc12
InChIKey: QPKSHJTZCXULAH-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using acetylthiocholine iodide as substrate preincubated for 6 mins followed by substrate addition measured upto 180 secs by Ellman's method
Measurement: IC50 = 6.8 nM (pChEMBL 8.170000076293945)
Descriptors: MW 440.03, ALogP 5.81, HBA 5, HBD 0, PSA 42.68, QED 0.32
Compound (SMILES): CC(C)C[C@H](NC(=O)OCC1CC2C=CC1C2)C(=O)N[C@@H](C[C@H]1CCNC1=O)C(O)S(=O)(=O)[O-].[Na+]
InChIKey: IEIHJXBWUDMYFX-HEGFQCLOSA-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 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 501.6, ALogP 0.56, HBA 7, HBD 5, PSA 171.13, QED 0.2
Compound (SMILES): O=C1NC(=S)S/C1=C\c1cnn(-c2cccnc2)c1
InChIKey: XITDUDYYAZYCHU-WMZJFQQLSA-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 = 87.2 nM (pChEMBL 7.059999942779541)
Descriptors: MW 288.36, ALogP 1.76, HBA 6, HBD 1, PSA 59.81, QED 0.67
Compound (SMILES): Cc1nnc(C)n1-c1ccccc1
InChIKey: KFRXOTJMJOHTJS-UHFFFAOYSA-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 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 173.22, ALogP 1.88, HBA 3, HBD 0, PSA 30.71, QED 0.66
Compound (SMILES): O=C(NCCN1C(=O)/C(=C/c2ccccc2O)SC1=S)c1cccc(Br)c1
InChIKey: SZSZAKFJMMBQRH-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 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 463.38, ALogP 3.79, HBA 5, HBD 2, PSA 69.64, QED 0.52
Compound (SMILES): COC(=O)c1ccccc1Cc1cn(C)nc1-c1cc(Cl)nc(N)n1
InChIKey: FIUGGTKIGCZJJN-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 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 357.8, ALogP 2.49, HBA 7, HBD 1, PSA 95.92, QED 0.57
Compound (SMILES): CC(C)=CCC/C(C)=C/OC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCNC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C
InChIKey: HEVZGFCDFBOLGJ-ZKOPLKQWSA-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 = 0.37 nM (pChEMBL 9.430000305175781)
Descriptors: MW 565.75, ALogP 5.76, HBA 7, HBD 2, PSA 123.27, QED 0.1
Compound (SMILES): O=c1c(O)c(-c2ccccc2-c2ccc(CNc3cc(C(F)(F)F)cc4c3CCCC4)cc2)c1=O
InChIKey: KVNHMLBROHADFQ-UHFFFAOYSA-N
Target: Type-2 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P50052
Assay: Inhibition of Angiotensin 2 binding to Angiotensin 2 receptor (unknown origin)
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 477.48, ALogP 5.83, HBA 4, HBD 2, PSA 66.4, QED 0.36
Compound (SMILES): O=C(Nc1c2c(cc3c1CCC3)CCC2)NS(=O)(=O)c1ccccn1
InChIKey: GXRZVKUWAJJBOA-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 = 1330 nM (pChEMBL 5.880000114440918)
Descriptors: MW 357.44, ALogP 2.57, HBA 4, HBD 2, PSA 88.16, QED 0.88
Compound (SMILES): COc1cccc2ccc(-c3cc(-c4ccc5cccc(OC)c5c4O)c4cccc(OC)c4c3O)c(O)c12
InChIKey: QNSPJOAEPRYOBU-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Binding affinity to PPARalpha (unknown origin) assessed as inhibition constant by Cheng-Prusoff equation analysis
Measurement: Ki = 9400 nM (pChEMBL 5.03000020980835)
Descriptors: MW 518.57, ALogP 7.62, HBA 6, HBD 3, PSA 88.38, QED 0.22
Compound (SMILES): O=c1[nH]c(SCc2ccc(-c3ccc(S(=O)(=O)NC4CC4)cc3)cc2F)nc2c1CCC2
InChIKey: VHCNBUHEBFGRER-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 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 471.58, ALogP 3.8, HBA 5, HBD 2, PSA 91.92, QED 0.4
Compound (SMILES): Cc1nc(C2=CN(C)C(=O)[C@H](C)c3ccc(OCCO)cc32)c[nH]1
InChIKey: JKHAONFZTKWYFI-LLVKDONJSA-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 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 327.38, ALogP 2.05, HBA 4, HBD 2, PSA 78.45, QED 0.9
Compound (SMILES): O=C(Nc1ccc2scnc2c1)C1CCN(S(=O)(=O)c2ccc(Cl)nc2)CC1
InChIKey: CRDVYCHPBMFHGT-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Antagonist activity at human muscarinic M5 receptor expressed in CHO cells in the presence of acetylcholine by calcium mobilisation assay
Measurement: IC50 = 168 nM (pChEMBL 6.78000020980835)
Descriptors: MW 436.95, ALogP 3.38, HBA 6, HBD 1, PSA 92.26, QED 0.63
Compound (SMILES): CC(C)(OCc1cc(-c2ccccc2)n(Cc2ccccc2)n1)C(=O)O
InChIKey: JQLGETSGYLPFRC-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Inhibition of MCT4 in human NCI-H358 cells
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 350.42, ALogP 3.98, HBA 4, HBD 1, PSA 64.35, QED 0.7
Compound (SMILES): Cc1ccc(C(=O)Nc2cc(F)cc(-c3cnn(C)c3)c2)cc1Nc1cc(-c2cccnc2)ccn1
InChIKey: WMIAPCITBFHJBA-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 478.53, ALogP 5.99, HBA 6, HBD 2, PSA 84.73, QED 0.31
Compound (SMILES): Cc1cc(SCc2c(C)noc2C)ncn1
InChIKey: ROKHJFVYDKKVDA-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 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 235.31, ALogP 2.68, HBA 5, HBD 0, PSA 51.81, QED 0.6
Compound (SMILES): COc1cccc2cc(-c3nc([C@H]4CC[C@H](C(=O)NCCOCCOCCNC(=O)CCOCCOCCOCCOCCn5cc(CCCCO[C@@H]6CC[C@@H](C[C@@H](C)[C@@H]7C[C@@H](OC)[C@H](C)/C=C(\C)[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)C/C=C\C=C\C=C(/C)[C@@H](OC)C[C@@H]8CC[C@@H](C)[C@@](O)(O8)C(=O)C(=O)N8CCCC[C@H]8C(=O)O7)C[C@H]6OC)nn5)CC4)n4ncnc(N)c34)[nH]c12
InChIKey: QEJYMWIIAFWDAS-UNCKKIIBSA-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 1834.31
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc(CN3CCN(C)CC3)c(C(F)(F)F)c2)cc1Nc1cc(-c2cncnc2)ccn1
InChIKey: PZSYBIBZJQZKSQ-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 = 10.1 nM (pChEMBL 8)
Descriptors: MW 561.61, ALogP 5.61, HBA 7, HBD 2, PSA 86.28, QED 0.3
Compound (SMILES): NC(=O)c1nn(CC(=O)N(CC(=O)NCc2cccc(Cl)c2F)C2CC2)c2ccc(NC(=O)N3CCN(Cc4ccc(F)cc4)CC3)cc12
InChIKey: BEQIHGYSIRUYPP-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 693.16, ALogP 3.72, HBA 7, HBD 3, PSA 145.9, QED 0.22
Compound (SMILES): C[C@]1(c2nc(-c3ccc(N)cc3)no2)CCCc2sc(N)c(C#N)c21
InChIKey: OTYSTCZFARVMKT-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): O=C1NC(=S)NC(=O)C1=Cc1cc(-c2ccc(C(F)(F)F)cc2)ccc1OCc1ccc(Cl)cc1
InChIKey: OBXFNBHKKGLMCN-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 = 3820 nM (pChEMBL 5.420000076293945)
Descriptors: MW 516.93, ALogP 5.52, HBA 4, HBD 2, PSA 67.43, QED 0.27
Compound (SMILES): COc1ccc(NC(=O)[C@H]2CCCN2C(=O)C2(c3cccc(Cl)c3)CCCC2)cc1
InChIKey: KQKHUZHQTMMBNU-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 = 100 nM (pChEMBL 7)
Descriptors: MW 426.94, ALogP 4.79, HBA 3, HBD 1, PSA 58.64, QED 0.75
Compound (SMILES): COc1ccc(Cl)cc1NC(=O)CN1CCN(S(=O)(=O)N2CCN(C(=O)N3CCCCCC3)CC2)CC1
InChIKey: RIINVHMXJQFFOU-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 557.12, ALogP 1.76, HBA 6, HBD 1, PSA 105.74, QED 0.57
Compound (SMILES): Nc1nc(Cl)cc(-c2nn(C(F)F)cc2Cc2ccccc2OCCN2CCO[C@@H](CO)C2)n1
InChIKey: MEYPLPIGBQTXRY-MRXNPFEDSA-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 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 494.93, ALogP 2.63, HBA 9, HBD 2, PSA 111.55, QED 0.44
Compound (SMILES): N.O=C(CS(=O)(=O)O)Nc1cc(Br)cc2ccccc12
InChIKey: VNUSTGGXCKNJJI-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 344.19, ALogP 2.43, HBA 3, HBD 2, PSA 83.47, QED 0.84
Compound (SMILES): NC(=O)c1nn(CC(=O)N(CC(=O)NCc2cccc(Cl)c2F)C2CC2)c2ccccc12
InChIKey: XSYBTZMVOZKEFF-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 457.89, ALogP 2.24, HBA 5, HBD 2, PSA 110.32, QED 0.54
Compound (SMILES): Cc1cccc2sc(N3C(=O)C(O)=C(C(=O)OC(C)(C)C)C3c3ccccc3)nc12
InChIKey: TUFPTUROJNQIKH-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 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 422.51, ALogP 4.85, HBA 6, HBD 1, PSA 79.73, QED 0.61
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cc3ccccc3n(C)c2=O)[nH]1
InChIKey: XLXMVDANDBLJOJ-RPBOFIJWSA-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 < 1.5 nM (pChEMBL 8.824000358581543)
Descriptors: MW 531.7, ALogP 4.75, HBA 6, HBD 2, PSA 100.09, QED 0.35
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(O)(CCC3CC3)c3ccccn3)ccc2F)c1
InChIKey: XXMBQXWQIGCREG-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 553.56, ALogP 5.56, HBA 6, HBD 3, PSA 106.06, QED 0.24
Compound (SMILES): O=c1[nH]c2ccc(OCc3ccc(F)cc3)cc2c(=O)o1
InChIKey: ORWQCVFRNYBMCB-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 = 122 nM (pChEMBL 6.909999847412109)
Descriptors: MW 287.25, ALogP 2.2, HBA 4, HBD 1, PSA 72.3, QED 0.8
Compound (SMILES): N[C@@H]1CCCC[C@H]1CNc1cc(Br)cc2[nH]ncc12
InChIKey: LBYNAJSMGGMTQB-JOYOIKCWSA-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 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 323.24, ALogP 3.25, HBA 3, HBD 3, PSA 66.73, QED 0.81
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(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(=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](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(=O)N[C@@H](C)C(N)=O
InChIKey: XIOAFDGKBAONSI-ZMYDTDHYSA-N
Target: Glucagon receptor (SINGLE PROTEIN), Mus musculus
UniProt: Q61606
Assay: Agonist activity at mouse GCGR expressed in CHO cells assessed as increase in cAMP accumulation
Measurement: EC50 = 6.06 nM (pChEMBL 8.220000267028809)
Descriptors: MW 4448.92
Compound (SMILES): C[C@H]1C(=O)N(C)C=Cc2cc(C(O)CO)ccc21
InChIKey: KMPKXTKTDWYWPO-CGCSKFHYSA-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 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 247.29, ALogP 1.26, HBA 3, HBD 2, PSA 60.77, QED 0.83
Compound (SMILES): C[C@H]1C(=O)N(C)C=C(c2cnn(C)c2)c2cc([C@@H](O)CO)ccc21
InChIKey: CJVJSGBELMMESS-DIFFPNOSSA-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 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 327.38, ALogP 1.41, HBA 5, HBD 2, PSA 78.59, QED 0.89
Compound (SMILES): COc1cccc(COc2ccc3[nH]c(=O)oc(=O)c3c2)c1
InChIKey: IIIKCQOXYZVIJQ-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 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 299.28, ALogP 2.07, HBA 5, HBD 1, PSA 81.53, QED 0.8
Compound (SMILES): CCOC(=O)C1=C(O)C(=O)N(c2nc3ccc(OC)cc3s2)C1c1ccc(-c2ccccc2)cc1
InChIKey: MOKCYHBYVXTFFL-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 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 486.55, ALogP 5.44, HBA 7, HBD 1, PSA 88.96, QED 0.37
Compound (SMILES): COc1cc(/C=C/c2ccc(OC(=O)N3CCN(C)CC3)cc2)cc(OC)c1
InChIKey: YWSJKFIAIYCDOK-SNAWJCMRSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P37136
Assay: Inhibition of Sprague-Dawley rat cortex AChE using acetylthiocholine iodide as substrate incubated for 15 mins in presence of iso-OMPA inhibitor by Ellman's method
Measurement: IC50 = 8580 nM (pChEMBL 5.070000171661377)
Descriptors: MW 382.46, ALogP 3.62, HBA 5, HBD 0, PSA 51.24, QED 0.74
Compound (SMILES): COc1ccc(-c2cc(NC(=O)c3ccc(C)c(Nc4cc(-c5ccc(OC)nc5)ccn4)c3)cc(C(F)(F)F)c2)cc1
InChIKey: YUNIOIXEAMKSKU-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 584.6, ALogP 8.15, HBA 6, HBD 2, PSA 85.37, QED 0.19
Compound (SMILES): Cc1cn(-c2cc(NC(=O)c3ccc(C)c(Nc4cc(-c5cnc6ccccc6c5)ccn4)c3)cc(C(F)(F)F)c2)cn1
InChIKey: UOZVHXDIRMGAFL-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 578.6, ALogP 8.11, HBA 6, HBD 2, PSA 84.73, QED 0.21
Compound (SMILES): COC(=O)CCC/C=C\C/C=C\C/C=C\CCOC(=O)Nc1ccc(Br)cc1
InChIKey: WLKKPAUNGPKJRE-HGUHJZMRSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate incubated for 30 mins by Ellman's method
Measurement: IC50 = 19200 nM (pChEMBL 4.71999979019165)
Descriptors: MW 450.37, ALogP 6.18, HBA 4, HBD 1, PSA 64.63, QED 0.23
Compound (SMILES): O=c1[nH]c(SCc2ccc(-c3ccc(S(=O)(=O)N4CCS(=O)(=O)CC4)cc3)cc2F)nc2c1CCC2
InChIKey: RWAFRZKMVICBLS-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 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 549.67, ALogP 2.78, HBA 7, HBD 1, PSA 117.27, QED 0.37
Compound (SMILES): COC(=O)c1cc(NC[C@@H]2CCCC[C@H]2O)c2cn[nH]c2c1
InChIKey: KLDSDQOCTARQQB-ZUZCIYMTSA-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 = 12590 nM (pChEMBL 4.900000095367432)
Descriptors: MW 303.36, ALogP 2.31, HBA 5, HBD 3, PSA 87.24, QED 0.75
Compound (SMILES): NC(=O)c1nn(CC(=O)N(CC(=O)NCc2cccc(Cl)c2F)C2CC2)c2cc(NC(=O)N3CCCC(F)(F)C3)ccc12
InChIKey: QBTCSHVRSPDVNF-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 620.03, ALogP 3.5, HBA 6, HBD 3, PSA 142.66, QED 0.34
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2ccc3nc(OC)ccc3c2)[nH]1
InChIKey: VOCUPJYYWCXUPO-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 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 531.7, ALogP 5.45, HBA 6, HBD 2, PSA 100.21, QED 0.3
Compound (SMILES): O=C(CS(=O)(=O)O)Nc1cc(Br)cc([N+](=O)[O-])c1
InChIKey: ODCYCDCSCZZIFI-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 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 339.12, ALogP 1.18, HBA 5, HBD 2, PSA 126.61, QED 0.48
Compound (SMILES): Cc1ccccc1Oc1cc(-n2c(=O)cc(C(F)(F)F)[nH]c2=O)c(F)cc1C
InChIKey: WLUPQTKPKBLULM-UHFFFAOYSA-N
Target: Branched-chain-amino-acid aminotransferase, cytosolic (SINGLE PROTEIN), Homo sapiens
UniProt: P54687
Assay: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 394.32, ALogP 4.09, HBA 4, HBD 1, PSA 64.09, QED 0.68
Compound (SMILES): CN(C)C(=O)C1CCC(Oc2nc(-c3ccc(N)nc3)nc(N3CCOCC3)n2)CC1
InChIKey: XZLBNRWBFQNOFI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant mTOR (unknown origin) using GFP-4E-BP1 as substrate preincubated for 15 mins followed by substrate addition measured after 1 hr by TR-FRET assay
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 427.51, ALogP 1.38, HBA 9, HBD 1, PSA 119.59, QED 0.75
Compound (SMILES): CSCC[C@@H]1NC(=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)NC(=O)[C@@H]2CCCN2C(=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)NC1=O
InChIKey: VTJIINYDGFTQFH-AMZDWXELSA-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 = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 2134.53
Compound (SMILES): CC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H]1CCCCC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C(=O)O)C(=O)O)C(N)=O)NC(=O)[C@H](Cc2ccc([N+](=O)[O-])cc2)NC(=O)[C@H](CCC(N)=O)NC1=O)C(C)C
InChIKey: UWUBSFPMKFWHGU-SMLZLRLCSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BQA1
Assay: Binding affinity to PRMT5/MEP50 (unknown origin) assessed as inhibition constant by FITC- Competitive binding assay
Measurement: Ki = 66000 nM (pChEMBL 4.179999828338623)
Descriptors: MW 1117.14
Compound (SMILES): NCc1cccc(-n2nc(C(F)(F)F)cc2C(=O)Nc2cc(C(N)(CCC3CC3)c3ccccc3)ccc2F)c1
InChIKey: NQFNNZJJOCPZCP-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 551.59, ALogP 6.13, HBA 5, HBD 3, PSA 98.96, QED 0.22
Compound (SMILES): O=C(O)c1cc(Nc2nc3ccccc3[nH]2)ccc1O
InChIKey: LNMNZIBGZFIFKF-UHFFFAOYSA-N
Target: ATP-dependent RNA helicase DDX3X (SINGLE PROTEIN), Homo sapiens
UniProt: O00571
Assay: Inhibition of recombinant DDX3X (unknown origin) helicase activity using 6-FAM-labeled dsRNA as substrate incubated for 30 mins by fluorescence based assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 269.26, ALogP 2.71, HBA 4, HBD 4, PSA 98.24, QED 0.55
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](CC(=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: KCTHVKFTDSSSQC-LSRYLGHRSA-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 = 0.12 nM (pChEMBL 9.920000076293945)
Descriptors: MW 3570.93
Compound (SMILES): COc1cc(C(=O)OCCCCCCN(CCCOC(=O)c2cc(OC)c(OC)c(OC)c2)CCCOc2ccc3ccc(=O)oc3c2)cc(OC)c1OC
InChIKey: IOPOLXYULUWSMW-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 preincubated for 10 mins and measured by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 765.85, ALogP 6.58, HBA 14, HBD 0, PSA 150.66, QED 0.04
Compound (SMILES): C#Cc1cc(C(=O)O)sc1SC
InChIKey: DTXCUCIQNPLERA-UHFFFAOYSA-N
Target: Kelch-like ECH-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14145
Assay: Binding affinity to Keap1 kelch domain (unknown origin) by surface plasmon resonance assay
Measurement: Kd = 480000 nM (pChEMBL 3.319999933242798)
Descriptors: MW 198.27, ALogP 2.15, HBA 3, HBD 1, PSA 37.3, QED 0.58
Compound (SMILES): CC(C)n1nc(-c2cc3cc(O)cc(F)c3[nH]2)c2c(N)ncnc21
InChIKey: LUKIMGGLSGHDAN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition Assay: Class I PI3-Ks can be either purchased (p110α/p85α, p110β/p85α, p110Î´/p85α from Upstate, and p110γ from Sigma) or expressed as previously described (Knight et al., 2004). IC50 values are measured using either a standard TLC assay for lipid kinase activity (described below) or a high-throughput membrane capture assay. Kinase reactions are performed by preparing a reaction mixture containing kinase, inhibitor (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 ug/ml). Reactions are initiated by the addition of ATP containing 10 uCi of γ-32P-ATP to a final concentration 10 or 100 uM and allowed to proceed for 5 minutes at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 ul 1N HCl followed by 160 ul CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase is transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3-4 hours in a 65:35 solution of n-propanol:1M acetic acid. The TLC plates are then dried, exposed to a phosphorimager screen (Storm, Amersham), and quantitated. For each compound, kinase activity is measured at 10-12 inhibitor concentrations representing two-fold dilutions from the highest concentration tested (typically, 200 uM).
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 326.34, ALogP 2.98, HBA 6, HBD 3, PSA 105.64, QED 0.52
Compound (SMILES): Cn1c([C@@H]2C[C@@H](OC(=O)NCCc3ccc(C(=O)NO)cc3)CN2c2nc(N)nc(N)c2C#N)nc2cccc(Cl)c2c1=O
InChIKey: MMFZSZCTPXEGCR-UZLBHIALSA-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 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 619.04, ALogP 1.82, HBA 13, HBD 5, PSA 227.4, QED 0.15
Compound (SMILES): CC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H]1CCCCCC[C@@H](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)Nc2ccc3c(c2)C(=O)OC32c3ccc(O)cc3Oc3cc(O)ccc32)C(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCC(N)=O)NC1=O)C(C)C
InChIKey: FXLAGHGNAGPJGH-YQFBZIEGSA-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 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 1545.69
Compound (SMILES): O=C(Nc1c2c(cc3c1CCC3)CCC2)NS(=O)(=O)c1cnn2c1OCCC2
InChIKey: KWSGPJCQWZMUQM-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 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 402.48, ALogP 2.15, HBA 6, HBD 2, PSA 102.32, QED 0.82
Compound (SMILES): CC1CCN(S(=O)(=O)N2CCN(CC(=O)Nc3ccccc3)CC2)CC1
InChIKey: MXGAMFCXOSZAJJ-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 380.51, ALogP 1.22, HBA 4, HBD 1, PSA 72.96, QED 0.83
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](CCS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc1ccccc1)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)O)C(C)C)C(C)C
InChIKey: HXROOIDQCQSPGK-DLOSMSPMSA-N
Target: Pituitary adenylate cyclase-activating polypeptide type I receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41586
Assay: Antagonist activity at PAC1R in human SH-SY5Y cells assessed as inhibition of PACAP38-induced cAMP accumulation pre-incubated for 30 mins followed by agonist addition and measured after 75 mins by Eu-cAMP tracer based LANCE ultra cAMP assay
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 4139.95
Compound (SMILES): Cc1cc(C)c(C(=O)N2CCN(c3ncccc3F)[C@H](CO)C2)cc1NC1CCN(c2ccccc2C#N)CC1
InChIKey: IEEJBCKDNGRROT-VWLOTQADSA-N
Target: mTORC1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BVC4
Assay: Inhibition of mTORC1 in human MCF7 cells assessed as measuring phosphorylated S6K1 incubated for 2 hrs by AlphaLISA assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 542.66, ALogP 4.11, HBA 7, HBD 2, PSA 95.73, QED 0.48
Compound (SMILES): N#Cc1cc(F)c(-n2c(=O)cc(C(F)(F)F)[nH]c2=O)cc1Oc1ccccc1
InChIKey: FAPWUYPGMPGMBQ-UHFFFAOYSA-N
Target: Branched-chain-amino-acid aminotransferase, cytosolic (SINGLE PROTEIN), Homo sapiens
UniProt: P54687
Assay: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 391.28, ALogP 3.35, HBA 5, HBD 1, PSA 87.88, QED 0.69
Compound (SMILES): COc1cc(/C=C/C(=O)OCCCCCCCN(CCCOC(=O)c2c3ccccc3cc3ccccc23)CCCOc2ccc3ccc(=O)oc3c2)cc(OC)c1OC
InChIKey: KAGJUCHTDFATOU-FCDQGJHFSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 preincubated for 10 mins and measured by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 815.96, ALogP 9.65, HBA 11, HBD 0, PSA 122.97, QED 0.02
Compound (SMILES): O=C(Nc1ccc2[nH]ncc2n1)[C@H]1C[C@@H](F)CN1C(=O)C1(c2ccc(Cl)cc2)CCC1
InChIKey: OSDVXRQBLRRNJD-CRAIPNDOSA-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 = 0.1995 nM (pChEMBL 9.699999809265137)
Descriptors: MW 441.89, ALogP 3.61, HBA 4, HBD 2, PSA 90.98, QED 0.65
Compound (SMILES): CC(C)c1snc(-c2c(Cl)cccc2Cl)c1COc1ccc(N(C)Cc2ccc(C(=O)O)cc2)c(C(F)(F)F)n1
InChIKey: VSACXXDOCBWKET-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR in HEK293T cells assessed as transcriptional activity by measuring fluorescence intensity by luciferase reporter assay
Measurement: EC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 610.49, ALogP 8.57, HBA 6, HBD 1, PSA 75.55, QED 0.2
Compound (SMILES): COc1cc(C#N)c(Oc2ccccc2C)cc1-n1c(=O)cc(C(F)(F)C(F)(F)F)[nH]c1=O
InChIKey: QPQFNJFXGFRYKV-UHFFFAOYSA-N
Target: Branched-chain-amino-acid aminotransferase, cytosolic (SINGLE PROTEIN), Homo sapiens
UniProt: P54687
Assay: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay
Measurement: IC50 = 792 nM (pChEMBL 6.099999904632568)
Descriptors: MW 467.35, ALogP 4.16, HBA 6, HBD 1, PSA 97.11, QED 0.57
Compound (SMILES): O=C(Nc1ccc2[nH]c(=O)[nH]c2c1)[C@H]1CCCN1C(=O)C1(c2cccc(Cl)c2)CCCC1
InChIKey: FEMLMPADWOFPRW-HXUWFJFHSA-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 = 0.3981 nM (pChEMBL 9.399999618530273)
Descriptors: MW 452.94, ALogP 3.95, HBA 3, HBD 3, PSA 98.06, QED 0.56
Compound (SMILES): CN(Cc1ccc(C(=O)O)cc1)c1ccc(OCc2c(-c3c(Cl)cccc3Cl)nsc2C2CC2)nc1C(F)(F)F
InChIKey: NYTRWEPOQXNVCK-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR in HEK293T cells assessed as transcriptional activity by measuring fluorescence intensity by luciferase reporter assay
Measurement: EC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 608.47, ALogP 8.32, HBA 6, HBD 1, PSA 75.55, QED 0.21
Compound (SMILES): Cc1cccc(C)c1Oc1cc(-n2c(=O)cc(C(F)(F)F)[nH]c2=O)c(F)cc1C#N
InChIKey: GDLJEMGHMVOECK-UHFFFAOYSA-N
Target: Branched-chain-amino-acid aminotransferase, cytosolic (SINGLE PROTEIN), Homo sapiens
UniProt: P54687
Assay: Inhibition of N-terminal his-tagged human recombinant BCAT1 expressed in Escherichia coli BL21(DE3) cells using leucine and alpha-KG as substrate in presence of NADH by fluorescence assay
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 419.33, ALogP 3.96, HBA 5, HBD 1, PSA 87.88, QED 0.65
Compound (SMILES): O=C(CCCCC1CCSS1)O[C@@H]1CO[C@H]2[C@@H]1OC[C@@H]2OC(=O)NCc1ccccc1
InChIKey: JHBSKKNCJSYZBP-ACLUHKAVSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human plasma BChE using butyrylthiocholine iodide as substrate preincubated for 30 mins followed by substrate addition measured after 5 mins by Ellman's method
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 467.61, ALogP 3.7, HBA 8, HBD 1, PSA 83.09, QED 0.33
Compound (SMILES): Cc1ncc(S(=O)(=O)NC(=O)Nc2c3c(cc4c2CCC4)CCC3)s1
InChIKey: JCFFSDANQNWAIV-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 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 377.49, ALogP 2.94, HBA 5, HBD 2, PSA 88.16, QED 0.86
Compound (SMILES): O=C(Nc1c2c(cc3c1CCC3)CCC2)NS(=O)(=O)c1nccs1
InChIKey: XSCXDJJEKMKGDD-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 = 3660 nM (pChEMBL 5.440000057220459)
Descriptors: MW 363.46, ALogP 2.63, HBA 5, HBD 2, PSA 88.16, QED 0.88
Compound (SMILES): O=C(Nc1ccc2scnc2c1)C1CCN(S(=O)(=O)c2ccc3c(c2)CCO3)CC1
InChIKey: DESJRPNWJIVCFE-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08911
Assay: Antagonist activity at rat muscarinic M5 receptor
Measurement: IC50 = 249 nM (pChEMBL 6.599999904632568)
Descriptors: MW 443.55, ALogP 3.27, HBA 6, HBD 1, PSA 88.6, QED 0.67
Compound (SMILES): O=C(Nc1ccc2[nH]ncc2n1)[C@H]1CCCN1C(=O)C1(c2cccc(Cl)c2)CCCC1
InChIKey: ZIFMZENSFYUYPH-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 = 0.1585 nM (pChEMBL 9.800000190734863)
Descriptors: MW 437.93, ALogP 4.05, HBA 4, HBD 2, PSA 90.98, QED 0.64
Compound (SMILES): NC(=O)c1nn(CC(=O)N(CC(=O)NCc2cccc(Cl)c2F)C2CC2)c2cc(C(=O)O)ccc12
InChIKey: VDHJFSYZOAJNSW-UHFFFAOYSA-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 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 501.9, ALogP 1.93, HBA 6, HBD 3, PSA 147.62, QED 0.41