lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)(C)NC(=O)C1C(=O)NCCN1C(=O)CCCN1CCN(c2cccc(Cl)c2Cl)CC1
InChIKey: APQWXABKECJSIH-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at human D2 receptor expressed in HEK293T cells assessed as beta-arrestin recruitment preincubated for 10 mins with coelenterazine followed by compound addition and measured after 10 mins by BRET assay
Measurement: EC50 = 0.3715 nM (pChEMBL 9.430000305175781)
Descriptors: MW 498.46, ALogP 2.14, HBA 5, HBD 2, PSA 84.99, QED 0.59
Compound (SMILES): CNCCNCc1cccc(-c2nc(Nc3ccccc3)c(C)c(-c3c(C)noc3C)n2)c1
InChIKey: DVIUIRPCVXVFSX-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA8
Assay: Inhibition of PRMT6 (unknown origin) incubated for 15 mins measured after 60 min by AlphaLISA assay
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 442.57, ALogP 4.78, HBA 7, HBD 3, PSA 87.9, QED 0.32
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CO)NC(=O)/C=N/OCc1ccc(S(N)(=O)=O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(N)=O)C(N)=O)C(C)C)[C@@H](C)O
InChIKey: OVYKBARNSMGXPZ-OLTRRQNTSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibition constant
Measurement: Ki = 25700 nM (pChEMBL 4.590000152587891)
Descriptors: MW 1179.32
Compound (SMILES): CCCCNNC(=O)c1ccc(F)cc1
InChIKey: YRLLWXIGAGZKFP-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 8634 nM (pChEMBL 5.059999942779541)
Descriptors: MW 210.25, ALogP 1.86, HBA 2, HBD 2, PSA 41.13, QED 0.58
Compound (SMILES): Cc1onc(-c2ccccc2)c1C(=O)NCCCCCNC(=O)C(C)(C)S
InChIKey: XJTVLNNVIZUFGI-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human full length recombinant HDAC6 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 389.52, ALogP 3.37, HBA 5, HBD 3, PSA 84.23, QED 0.45
Compound (SMILES): O=C(OC[C@@H](Cc1ccccc1)NS(=O)(=O)c1ccc(Br)cc1)[C@@H](Cc1ccccc1)NS(=O)(=O)c1ccccc1
InChIKey: ULQDLVLVQKVZBG-GGXMVOPNSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 657.61, ALogP 4.47, HBA 6, HBD 2, PSA 118.64, QED 0.21
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(CC)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: FDTGYJGRULJHQZ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR Exon 21 L858R and Exon 20 T790M Concurrent Mutations: A compound's ability in selectively inhibiting EGFR L858R and T790M concurrent mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with EGFR L858R and T790M double mutations. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR L858R and T790M double mutation, was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR L858R and T790M double mutations. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR L858R and T790M double mutation virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing EGFR L858R and T790M double mutation (named Ba/F3-EGFR L858R/T790M) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-EGFR L858R/T790M cells seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega; this assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives). Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 599.74, ALogP 5.56, HBA 10, HBD 2, PSA 113.85, QED 0.15
Compound (SMILES): O=C(CNc1cc(Cl)cc(Cl)c1)N1CC[C@H]2CCN(c3ncnc4[nH]ccc34)[C@H]2C1
InChIKey: ZJKAMIGVAPQVOU-UGSOOPFHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate measured after 15 mins in the presence of NADPH by LC/MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 445.35, ALogP 3.8, HBA 5, HBD 2, PSA 77.15, QED 0.64
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c5c(C)csc5c4)nn32)CC1
InChIKey: ZDWLIFUKOJCBAL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubated for 3 hrs by HTRF-based analysis
Measurement: IC50 = 22.1 nM (pChEMBL 7.659999847412109)
Descriptors: MW 479.61, ALogP 3.96, HBA 7, HBD 2, PSA 102.48, QED 0.54
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4cccnc4)n3)cc2C(F)(F)F)CC1
InChIKey: JWOVGKOVFZNPSO-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin A (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human Cdk2/Cyclin A using Myelin basic protein as substrate by ATP competitive assay
Measurement: IC50 = 9300 nM (pChEMBL 5.03000020980835)
Descriptors: MW 414.44, ALogP 4.05, HBA 6, HBD 1, PSA 57.18, QED 0.7
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3cc(COC4CC4)c(=O)n(C4CCCC4)c3n2)CC1
InChIKey: YAGWJHKKLYYWQN-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin-T1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki > 1400 nM (pChEMBL 5.854000091552734)
Descriptors: MW 461.59, ALogP 2.42, HBA 8, HBD 1, PSA 106.42, QED 0.67
Compound (SMILES): CNc1cc(-c2ccnc(Nc3ccc(N4CCN(C)CC4)c(C(F)(F)F)c3)n2)ccn1
InChIKey: KHBUJYBNSDDNHK-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin A (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human Cdk2/Cyclin A using Myelin basic protein as substrate by ATP competitive assay
Measurement: IC50 = 39000 nM (pChEMBL 4.409999847412109)
Descriptors: MW 443.48, ALogP 4.09, HBA 7, HBD 2, PSA 69.21, QED 0.62
Compound (SMILES): O=C([O-])CNC(=O)c1ccc(S(=O)(=O)N2CCC(c3ccc(Cl)cc3)CC2)cn1.[K+]
InChIKey: DJLPNUNUNPABGA-UHFFFAOYSA-M
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Binding affinity to biotinylated HDAC6 zinc finger ubiquitin binding domain (1109 to 1215 residues) (unknown origin) expressed in Escherichia coli incubated for 120 secs by Biolayer Interferometry assay
Measurement: Kd > 100000 nM (pChEMBL 4)
Descriptors: MW 437.91, ALogP 2.12, HBA 5, HBD 2, PSA 116.67, QED 0.71
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@H](O)COC[C@H](Cc2ccccc2)NC(=O)c2ccncc2)CC1
InChIKey: JEJVZDGRLIYMOS-SVBPBHIXSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 499.62, ALogP 2.49, HBA 7, HBD 2, PSA 101.72, QED 0.42
Compound (SMILES): COc1cc(/C=C2/CN(C(C)=O)C(Cc3ccccc3)CN2C(=O)c2ccccc2)cc2c1OCO2
InChIKey: NOOJBZHDPURBGQ-QFEZKATASA-N
Target: Sterol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75908
Assay: Inhibition of SOAT2 (unknown origin)
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 484.55, ALogP 4.38, HBA 5, HBD 0, PSA 68.31, QED 0.54
Compound (SMILES): CCN(Cc1cc(C)n(C[C@@H]2C[C@H]2C#N)c(=O)c1)c1ccc(F)cc1
InChIKey: DGIGAYPQXQSHGW-IRXDYDNUSA-N
Target: Glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P42262
Assay: Displacement of [3H]-HBT1 from His-tagged GluA2-AMPA receptor LBD (unknown origin) in presence of glutamate by scintillation proximity assay
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 339.41, ALogP 3.48, HBA 4, HBD 0, PSA 49.03, QED 0.81
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCN(/C(=N/O)c3ccc(F)cc3)CC2)cc1
InChIKey: ZLWIKBNNYLCANS-LVZFUZTISA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant carbonic anhydrase 12 assessed as inhibition constant preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 106.2 nM (pChEMBL 6.96999979019165)
Descriptors: MW 378.43, ALogP 1.43, HBA 5, HBD 2, PSA 99.23, QED 0.36
Compound (SMILES): O=C1N[C@H]2C[C@@H](C2)OCc2cccc(n2)Nc2cc([nH]n2)[C@H]2CC[C@H](C2)O1
InChIKey: LAQCQSKKZIRXFW-MHEUCROKSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) assessed as inhibition of substrate peptide phosphorylation using MBP as peptide substrate incubated for 2 hrs in presence of ATP by Lance Ultra HTRF assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 369.43, ALogP 2.97, HBA 6, HBD 3, PSA 101.16, QED 0.66
Compound (SMILES): O=c1[nH]c(/C=C/c2cccc(F)c2)nc2ccccc12
InChIKey: ZFGIVIZXCYOWBK-CMDGGOBGSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK4/Cyclin D3 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 266.27, ALogP 3.23, HBA 2, HBD 1, PSA 45.75, QED 0.77
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@@H](O)COC[C@@H](Cc2ccccc2)NC(=O)C2CCN(C(=O)OCc3ccccc3)CC2)CC1
InChIKey: FCORXOBTLFNQOU-KKLWWLSJSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 639.8, ALogP 3.83, HBA 8, HBD 2, PSA 118.37, QED 0.29
Compound (SMILES): NCCCC[C@H](NC(=O)C(NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)C(c1ccccc1)c1ccccc1)C(N)=O
InChIKey: GGAKLYWEFZCVIT-NIEMNNIISA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes using paclitaxel as substrate assessed as reduction in substrate hydroxylation incubated for 5 mins in presence of beta-NADPH measured by LC-MS/MS analysis
Measurement: IC50 = 10200 nM (pChEMBL 4.989999771118164)
Descriptors: MW 1439.82
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3c(C)nn(C)c3C#N)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: YXFNNHJWPFANTQ-OALUTQOASA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12851
Assay: Inhibition of MAP4K2 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 356 nM (pChEMBL 6.449999809265137)
Descriptors: MW 556.6, ALogP 3.02, HBA 10, HBD 3, PSA 155.21, QED 0.31
Compound (SMILES): CCCN(CCc1ccc(CCN(CCC)[C@H]2CCc3nc(N)sc3C2)cc1)[C@H]1CCc2c(O)cccc2C1
InChIKey: SGWUMXOWOUGLMJ-NSOVKSMOSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Agonist activity at human D3 receptor expressed in CHO cells assessed as stimulation of [35S]GTPgammaS binding by Perkin elmer analysis
Measurement: EC50 = 13.3 nM (pChEMBL 7.880000114440918)
Descriptors: MW 546.83, ALogP 6.05, HBA 6, HBD 2, PSA 65.62, QED 0.29
Compound (SMILES): COc1ccc(/C=C/C(=O)NC[C@@H](Cc2ccccc2)NS(=O)(=O)c2ccc(C(F)(F)F)cc2)cc1OC
InChIKey: BGZOWQGJIQJZCF-YTIHOSAGSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 548.58, ALogP 4.44, HBA 5, HBD 2, PSA 93.73, QED 0.35
Compound (SMILES): Cc1cc(OC(F)F)ccc1NC(=O)c1cc(C(=O)NCc2ccc(F)cc2)c(F)cc1Cl
InChIKey: NFAGOVIQVGGRKR-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Inverse agonist activity at human PPARgamma expressed in CHO cells co-expressing GAL4-NHR-LBD assessed as transcriptional repression preincubated for 6 hrs followed by luciferin addition by luminescence method
Measurement: IC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 480.85, ALogP 5.71, HBA 3, HBD 2, PSA 67.43, QED 0.43
Compound (SMILES): Fc1ccc(Cl)c(Sc2n[nH]c3ncc(-c4cnn(C5CCNCC5)c4)cc23)c1Cl
InChIKey: FCLVBOUURHAHBG-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK L1196M mutant (unknown origin) using biotin-TK peptide as substrate in presence of ATP incubated for 90 mins by HTRF assay
Measurement: IC50 = 578 nM (pChEMBL 6.239999771118164)
Descriptors: MW 463.37, ALogP 5.34, HBA 6, HBD 2, PSA 71.42, QED 0.4
Compound (SMILES): C[C@@]12CC[C@@H]3c4ccc(OCCCN5CCCC5)cc4CC[C@H]3[C@@H]1CCC2N1CCCC1
InChIKey: PUEQNBHYHQKBQD-YORHAQRYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Displacement of N-alpha-[methyl-3H]-methylhistamine dihydrochloride from Sprague-Dawley rat brain membrane histamine H3 receptor assessed as inhibition constant incubated for 30 mins by liquid scintillation counting analysis
Measurement: Ki = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 436.68, ALogP 5.87, HBA 3, HBD 0, PSA 15.71, QED 0.52
Compound (SMILES): Clc1ccc(-n2cc(CNC[C@@H]3CCCOC3)nn2)c(Cl)c1
InChIKey: VSIADCQRJWOKCW-NSHDSACASA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Agonist activity at D4R (unknown origin) by camp reporter assay
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 341.24, ALogP 3.09, HBA 5, HBD 1, PSA 51.97, QED 0.91
Compound (SMILES): C=CC(=O)Nc1ccc2[nH]c(=O)n(C3CCN(Cc4ccc(-c5nc(C)c(=O)[nH]c5-c5ccccc5)cc4)CC3)c2c1
InChIKey: VDTRPZUYLDIREH-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Binding affinity to N-terminal His6-tagged TEV protease fused wild-type AKT1 (2 to 446 residues) (unknown origin) expressed in Sf9 cells assessed as inhibition constant
Measurement: Ki = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 560.66, ALogP 5.02, HBA 6, HBD 3, PSA 115.88, QED 0.24
Compound (SMILES): O=C(O)c1cc(-c2ccc(/C=N/Nc3nc4nonc4nc3Nc3ccccc3)o2)ccc1Cl
InChIKey: BKOFAWBQRGSHGD-BHGWPJFGSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGF-R2 (unknown origin)
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 475.85, ALogP 4.81, HBA 10, HBD 3, PSA 151.56, QED 0.22
Compound (SMILES): O=C(O)c1ccc2c(c1)nc(NCc1ccccc1)c1ncccc12
InChIKey: VBKHXXPYOSWXSA-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Inhibition of wild type human CK2alpha' in presence of ATP by radiometric kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 329.36, ALogP 4.09, HBA 4, HBD 2, PSA 75.11, QED 0.55
Compound (SMILES): CP(C)(=O)c1ccccc1-c1ccc(N2CC(CO)[C@@H](NC(=O)Nc3ccc(Cl)cc3F)C2=O)c(F)c1F
InChIKey: UDKGTLKMPMSTQV-PYFQUHSISA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: FPR2 and FPR1 Cyclic Adenosine Monophosphate (cAMP) Assays: A mixture of forskolin (5 μM final for FPR2 or 10 μM final for FPR1) and IBMX (200 μM final) were added to 384-well Proxiplates (Perkin-Elmer) pre-dotted with test compounds in DMSO (1% final) at final concentrations in the range of 0.020 nM to 100 μM. Chinese Hamster Ovary cells (CHO) overexpressing human FPR1 or human FPR2 receptors were cultured in F-12 (Ham's) medium supplemented with 10% qualified FBS, 250 μg/ml zeocin and 300 μg/ml hygromycin (Life Technologies). Reactions were initiated by adding 2,000 human FPR2 cells per well or 4,000 human FPR1 cells per well in Dulbecco's PBS (with calcium and magnesium) (Life Technologies) supplemented with 0.1% BSA (Perkin-Elmer). The reaction mixtures were incubated for 30 min at room temperature. The level of intracellular cAMP was determined using the HTRF HiRange cAMP assay reagent kit (Cisbio) according to manufacturer's instruction. Solutions of cryptate conjugated anti-cAMP and d2 fluorophore-labelled cAMP were made in a supplied lysis buffer separately. Upon completion of the reaction, the cells were lysed with equal volume of the d2-cAMP solution and anti-cAMP solution. After a 1-h room temperature incubation, time-resolved fluorescence intensity was measured using the Envision (Perkin-Elmer) at 400 nm excitation and dual emission at 590 nm and 665 nm. A calibration curve was constructed with an external cAMP standard at concentrations ranging from 1 μM to 0.1 pM by plotting the fluorescent intensity ratio from 665 nm emission to the intensity from the 590 nm emission against cAMP concentrations. The potency and activity of a compound to inhibit cAMP production was then determined by fitting to a 4-parametric logistic equation from a plot of cAMP level versus compound concentrations.
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 565.92, ALogP 4.82, HBA 4, HBD 3, PSA 98.74, QED 0.37
Compound (SMILES): NS(=O)(=O)c1ccc(-n2cc(COC(=O)c3ccc4c(c3)C(=O)N(c3ccccc3Cl)C4=O)nn2)cc1
InChIKey: MSUMULVHTXISHH-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human transmembrane carbonic anhydrase 9 using 4-nitrophenyl acetate as substrate assessed as inhibition constant by spectrophotometric analysis
Measurement: Ki = 18.6 nM (pChEMBL 7.730000019073486)
Descriptors: MW 537.94, ALogP 2.73, HBA 9, HBD 1, PSA 154.55, QED 0.29
Compound (SMILES): CNCc1cc(C)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(F)c1
InChIKey: YZXSIGGVKBZQGJ-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TrkA (unknown origin) in presence of ATP
Measurement: IC50 = 1624 nM (pChEMBL 5.789999961853027)
Descriptors: MW 350.4, ALogP 3.19, HBA 5, HBD 2, PSA 71.42, QED 0.59
Compound (SMILES): CC(C)=CCc1ccc(O)c([C@]2(O)c3c(O)cc(C)cc3C(=O)C2(C)C)c1O
InChIKey: JIIKZACQDAPJRU-HSZRJFAPSA-N
Target: Sterol O-acyltransferase 2 (SINGLE PROTEIN), Chlorocebus aethiops
UniProt: O77759
Assay: Inhibition of african green monkey SAOT2 in CHO cells assessed as reduction cholesteryl ester synthesis
Measurement: IC50 = 6100 nM (pChEMBL 5.210000038146973)
Descriptors: MW 382.46, ALogP 4.08, HBA 5, HBD 4, PSA 97.99, QED 0.6
Compound (SMILES): CC[C@H]1CN(c2nc3ccc(Cl)cc3s2)CCC1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: KDIUXOKNJHLPLN-BHWOMJMDSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Mus musculus
UniProt: P35396
Assay: Agonist activity at Gal4-fused mouse PPAR-delta ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 493.46, ALogP 6.55, HBA 5, HBD 1, PSA 62.66, QED 0.39
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c(C5CC5)c(OC)c4)nn32)CC1
InChIKey: NVDXHXCRQAOJQR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubated for 3 hrs by HTRF-based analysis
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 479.58, ALogP 3.32, HBA 7, HBD 2, PSA 111.71, QED 0.59
Compound (SMILES): C=C1CC[C@@H](O[C@H]2C[C@@](O)([C@H](C)NC(=O)c3[nH]c(C)c(Cl)c3Cl)[C@H](O)[C@@H](C)O2)[C@@H]2CC[C@H](C)[C@H](/C(O)=C3\C(=O)[C@H](C(C)C)N([C@@H]4O[C@@H](C)[C@@H](OC(N)=O)[C@@H](OC(C)=O)[C@H]4OC)C3=O)[C@@H]12
InChIKey: NTNKQRBKOGURQE-BWWOCIMWSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES4
Assay: Inhibition of Escherichia coli DNA gyrase supercoiling activity using relaxed pBR322 DNA as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 941.9, ALogP 4.39, HBA 14, HBD 6, PSA 258.5, QED 0.06
Compound (SMILES): COc1ccc(COc2cccc3ccc(C(=O)NCc4ccc(C(=O)NO)cc4)nc23)cc1
InChIKey: JRPMIIFAHPIZMV-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) using Boc-Lys(Ac)-AMC or Boc-Lys(Tfa)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 1 hr by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 457.49, ALogP 3.87, HBA 6, HBD 3, PSA 109.78, QED 0.27
Compound (SMILES): CN1CC2CCC(C1=O)N2c1ncc2[nH]nc(-c3cnn(CCN4CCOCC4)c3)c2n1
InChIKey: LSRBAFLNXOUPIC-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: HTRF Assay (100 uM ATP): ALK2 (aa 147-end) was obtained from BPS biosciences. The enzymatic assays were conducted in white 384-well polystyrene plates in a final volume of 8 μL. The inhibitors were serially diluted in DMSO and added to the plate wells prior to addition of the other reaction components. The assays were carried out at 25° C. in the assay buffer (50 mM HEPES, pH 7.1, 10% Glycerol, 0.01% Brij50, 10 mM MgCl2, 1 mM EGTA, 5 mM DTT, and 0.01% BSA), containing 50 nM LANCE Ultra ULight-DNA Topoisomerase 2-alpha peptide (Perkin Elmer TRF0130), and 100 uM ATP. The final concentration of DMSO in the assay was 1% and the enzyme concentration was 2.5 nM for ALK2. The reactions were allowed to proceed for 2-4 hr after which, the reaction was quenched by addition of EDTA at a final concentration of 20 mM along with 1.5 nM LANCE Ultra Europium-anti-phospho-DNA Topoisomerase 2-alpha (Thr1342) antibody (Perkin Elmer TRF0218). The reaction was read on a PHERAstar FS plate reader (BMG Labtech). IC50 determination was performed by fitting percent control activity versus the log of the inhibitor concentration using the IDBS XLFit and GraphPad Prism 5.0 software.
Measurement: IC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 437.51, ALogP 0.36, HBA 9, HBD 1, PSA 108.3, QED 0.61
Compound (SMILES): O=C(Nc1cnccc1C(F)(F)F)c1ccnc(NC(=O)C2CC2)c1
InChIKey: KDUHTFCGEYDKBT-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: Inhibition of GST tagged GSK-3alpha (unknown origin) incubated for 1 hrs by HTRF assay
Measurement: IC50 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 350.3, ALogP 3.1, HBA 4, HBD 2, PSA 83.98, QED 0.89
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H]1CSC[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(N)=O)NC(=O)CNC(=O)[C@@H](Cc2c[nH]c3ccccc23)C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(C)C)NC1=O)[C@@H](C)CC
InChIKey: AXUOIRLEFGBIDH-YQQUIGGJSA-N
Target: Albumin (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: P49065
Assay: Binding affinity to rabbit albumin assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 320 nM (pChEMBL 6.5)
Descriptors: MW 2224.53
Compound (SMILES): CCN([C@@H](C(=O)O)C(C)C)S(=O)(=O)c1ccc(-c2nc(-c3ccc(C)s3)no2)cc1
InChIKey: ZVQKPPCVSXIXMD-QGZVFWFLSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of human recombinant MMP-9 (20 to 707 residues) Gln279Arg mutant expressed in CHO cells using (7-methoxycoumarin-4-y1)-acetyl-Pro-Leu-Gly-Leu-[3-(2,4-dinitropheny1)-L-2,3-diaminopropionyl]-Ala-Arg-NH2 as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 10 mins by fluorescence based analysis
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 449.55, ALogP 3.89, HBA 7, HBD 1, PSA 113.6, QED 0.55
Compound (SMILES): CCCC(CCC)Oc1ccc(-c2ccccc2-c2nn[nH]n2)cc1NC(=O)Nc1ccc(C)cc1
InChIKey: GWYRYMVYQSUKAK-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 484.6, ALogP 6.83, HBA 5, HBD 3, PSA 104.82, QED 0.23
Compound (SMILES): Cc1ccc2cccnc2c1S(=O)(=O)Nc1ccccc1C#Cc1ccc(C(=O)O)nc1
InChIKey: NZNLHBUIPSPALM-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Inhibition of human MCT4 in human MDA-MB-231 cells assessed as inhibition of radioactive lactate efflux preincubated for 30 mins followed by D(+)glucose and measured after 4 hrs by dialysis based UHPLC-ESI-Q-Orbitrap-MS analysis
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 443.48, ALogP 3.84, HBA 5, HBD 2, PSA 109.25, QED 0.46
Compound (SMILES): O=C(CCCN1CCC(N2CC(=O)N3C(Cc4c([nH]c5ccccc45)C3c3ccc4c(c3)OCO4)C2=O)CC1)NO
InChIKey: JONSWONOTIBALH-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 559.62, ALogP 2.33, HBA 7, HBD 3, PSA 127.44, QED 0.31
Compound (SMILES): CC(O)(CCCc1ccccc1)c1cc(C(=O)N2Cc3ccccc3C2)ccc1O
InChIKey: LMAOUHXCKLNUDD-UHFFFAOYSA-N
Target: Heat shock protein 75 kDa, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q12931
Assay: Binding affinity to Trap1 (unknown origin) incubated for 24 hrs by fluorescence polarization assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 401.51, ALogP 4.78, HBA 3, HBD 2, PSA 60.77, QED 0.62
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCCN6CCC(OC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: ONOZLVJQXQZLPL-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M4 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 1039.63
Compound (SMILES): N#Cc1cccc(-c2ccc3ncc(-c4cc(F)cc(F)c4)c(N4CCC(N)CC4)c3c2)c1O
InChIKey: GHILNKWBALQPDP-UHFFFAOYSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Agonist activity at human SST3 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 456.5, ALogP 5.35, HBA 5, HBD 2, PSA 86.17, QED 0.43
Compound (SMILES): CCCCc1ccc(-c2ccc(-c3cc(C(=O)O)c4cc(Br)ccc4n3)o2)cc1
InChIKey: QXOMZRAYIBZPJH-UHFFFAOYSA-N
Target: Eukaryotic initiation factor 4A-I (SINGLE PROTEIN), Homo sapiens
UniProt: P60842
Assay: Inhibition of helicase activity of human recombinant N-terminal His6-tagged eIF4A expressed in Escherichia coli BL21 CodonPlus cells using Cy3-labeled RNA strand and unlabeled DNA strand by native PAGE analysis
Measurement: IC50 = 28700 nM (pChEMBL 4.539999961853027)
Descriptors: MW 450.33, ALogP 6.97, HBA 3, HBD 1, PSA 63.33, QED 0.34
Compound (SMILES): O=C(Nc1ccc(-c2ccc(F)cn2)cc1)c1cc2sc(NCCN3CCOCC3)nc2s1
InChIKey: RKMXNTQXGVOORY-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 7410 nM (pChEMBL 5.130000114440918)
Descriptors: MW 483.59, ALogP 4.56, HBA 8, HBD 2, PSA 79.38, QED 0.4
Compound (SMILES): O=C(CCCNC(=O)c1cccc(C(=O)NCCCC(=O)NCCC[C@@H](NS(=O)(=O)c2ccc(OCc3cc(Br)cc(Br)c3)cc2)C(=O)NO)c1)NCCC[C@@H](NS(=O)(=O)c1ccc(OCc2cc(Br)cc(Br)c2)cc1)C(=O)NO
InChIKey: JQLHAXGMYALIFJ-AWSIMMLFSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of human recombinant MMP-9 expressed in CHO cells using Mca-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2 as substrate preincubated with enzyme for 3 hrs followed by substrate addition and measured every 10 secs for 15 mins by fluorescence based analysis
Measurement: IC50 = 3320 nM (pChEMBL 5.480000019073486)
Descriptors: MW 1402.83
Compound (SMILES): O=C[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@@H]1[C@H]2CCC[C@H]2CN1C(=O)COc1ccc(Cl)c(Cl)c1
InChIKey: LQMJXKADORALLN-ICWLNENESA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of recombinant SARS-CoV-2 3CLp using fluorogenic substrate by microplate reader
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 496.39, ALogP 2.21, HBA 5, HBD 2, PSA 104.81, QED 0.54
Compound (SMILES): CCOC1=CS(=O)(=O)c2cc3c(Nc4ccc5scnc5c4)ncnc3cc21
InChIKey: DGOLQKDWHOHSFK-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y572
Assay: Binding affinity to RIPK3 (unknown origin) assessed as dissociation constant by kinomescan assay
Measurement: Kd = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 410.48, ALogP 4.11, HBA 8, HBD 1, PSA 94.07, QED 0.54
Compound (SMILES): C[C@H]1CO[C@@H](c2ccc(N)nc2)CN1CC[C@@H]1CC[C@H](CNC(=O)c2cc3ccccc3[nH]2)C1
InChIKey: QIUNPJREZURMGC-AJGMTHFWSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-methylscopolamine from human dopamine D3 receptor expressed in HEK293 cell membranes incubated for 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 87.6 nM (pChEMBL 7.059999942779541)
Descriptors: MW 461.61, ALogP 4.14, HBA 5, HBD 3, PSA 96.27, QED 0.49
Compound (SMILES): CC(C)(C(=O)Nc1ccc(-c2cncc(C(F)(F)F)n2)cc1F)c1csc(NS(=O)(=O)C2CC2)n1
InChIKey: OKFGIMQRDHOBOP-UHFFFAOYSA-N
Target: CTP synthase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U2N0
Assay: Inhibition of rat CTPS2 preincubated for 10 mins followed by substrate addition and measured after 30 to 60 mins by RFMS assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 529.54, ALogP 4.58, HBA 7, HBD 2, PSA 113.94, QED 0.43
Compound (SMILES): COc1ccc2[nH]cc(CCNC(=O)CN(CCCCC3CCN(Cc4ccccc4)CC3)C(=O)c3cc(=O)c4ccccc4o3)c2c1
InChIKey: LHSUEACWFJGZKG-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human MAO-A using kynuramine as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by spectroscopic analysis
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 648.8, ALogP 6.17, HBA 6, HBD 2, PSA 107.88, QED 0.14
Compound (SMILES): CCCOc1ccc2c(c1)C(=O)CC1(CCN(c3ccc(S(N)(=O)=O)cc3[N+](=O)[O-])CC1)O2
InChIKey: JHHSEVNLVXISKA-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant
Measurement: Ki = 1242 nM (pChEMBL 5.909999847412109)
Descriptors: MW 475.52, ALogP 3.04, HBA 8, HBD 1, PSA 142.07, QED 0.5
Compound (SMILES): C=C1CC[C@@H](O[C@H]2C[C@@](O)([C@H](C)NC(=O)c3[nH]cc(Cl)c3Cl)[C@H](O)[C@@H](C)O2)[C@@H]2CC[C@H](C)[C@H](/C(O)=C3\C(=O)[C@H](C(C)C)N([C@@H]4O[C@@H](C)[C@@H](OC(N)=O)[C@@H](OC(C)=O)[C@H]4OC)C3=O)[C@@H]12
InChIKey: LGQLJKHATNDFOW-CZSJUKBWSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES4
Assay: Inhibition of Escherichia coli DNA gyrase supercoiling activity using relaxed pBR322 DNA as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 927.87, ALogP 4.08, HBA 14, HBD 6, PSA 258.5, QED 0.06
Compound (SMILES): CC(C)n1nc(-c2nnc(C3CCN(CCCO)CC3)o2)c2ccccc21.O=C(O)C(=O)O
InChIKey: UUNYODPWYANEIK-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate incubated for 12 mins in presence of NADPH regenerating system by LC-MS/MS analysis
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 369.47, ALogP 3.23, HBA 7, HBD 1, PSA 80.21, QED 0.72
Compound (SMILES): COc1c(CC=C(C)C)c(=O)[nH]c2c(OC)c(O)ccc12
InChIKey: AZFKJXQYMUMVEP-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at GST-tagged PPAR-gamma ligand binding domain (unknown origin) assessed as recruitment of fluorescein-labeled SRC3 coactivator peptide by LanthaScreen TR-FRET Coactivator assay
Measurement: EC50 = 15500 nM (pChEMBL 4.809999942779541)
Descriptors: MW 289.33, ALogP 2.76, HBA 4, HBD 2, PSA 71.55, QED 0.85
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OCC)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: FCZMHSXKERLEIN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR Exon 19 Deletion and Exon 20 T790M Concurrent Mutations: A compound's ability in selectively inhibiting EGFR exon 19 deletion and T790M concurrent mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with EGFR exon 19 deletion and T790M mutation. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR E746-A750 deletion and T790M Mutation, was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR exon 19 deletion and T790M mutations. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR E746-A750 deletion and T790M Mutation virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing EGFR E746-A750 deletion and T790M Mutation (named Ba/F3-EGFR-Del/T790M) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-EGFR-Del/T790M cells seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega; this assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives). Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 571.68, ALogP 4.69, HBA 10, HBD 2, PSA 113.85, QED 0.18
Compound (SMILES): O=C(Cc1ccc(-c2n[nH]c(=O)c3ccccc23)cc1)N1CCc2ccccc21
InChIKey: COYVFENBIAJDFY-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as ROCK inhibitors can be determined in a 30 μL assay containing 20 mM HEPES, pH 7.5, 20 mM MgCl2, 0.015% Brij-35, 4 mM DTT, 5 μM ATP and 1.5 μM peptide substrate (FITC-AHA-AKRRRLSSLRA-OH). Compounds were dissolved in DMSO so that the final concentration of DMSO was <2%, and the reaction was initiated with Rho kinase variants. After incubation, the reaction was terminated by the addition of EDTA and the phosphorylated and non-phosphorylated peptides separated using a LABCHIP® 3000 Reader (Caliper Life Sciences). Controls consisted of assays that did not contain compound, and backgrounds consisted of assays that contained enzyme and substrate but had EDTA from the beginning of the reaction to inhibit kinase activity. Compounds were tested in dose-response format, and the inhibition of kinase activity was calculated at each concentration of compound. The inhibition data were fit using a curve-fitting program to determine the IC50; i.e., the concentration of compound required to inhibit 50% of kinase activity.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 381.44, ALogP 3.72, HBA 3, HBD 1, PSA 66.06, QED 0.59
Compound (SMILES): COc1cc(CCc2ccccc2)c(C(=O)O)c(O)c1C/C=C(\C)CC=C(C)C
InChIKey: WNQYHTVUADEJHB-LDADJPATSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at PPARdelta (unknown origin)
Measurement: EC50 = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 394.51, ALogP 5.73, HBA 3, HBD 2, PSA 66.76, QED 0.53
Compound (SMILES): CN(CC(=O)NC1CCCCC1)C(=O)CCCN1CCN(c2cccc(Cl)c2Cl)CC1
InChIKey: ZQUYISBPDUWNLC-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at human D2 receptor expressed in HEK293T cells assessed as beta-arrestin recruitment preincubated for 10 mins with coelenterazine followed by compound addition and measured after 10 mins by BRET assay
Measurement: EC50 = 2.344 nM (pChEMBL 8.630000114440918)
Descriptors: MW 469.46, ALogP 3.8, HBA 4, HBD 1, PSA 55.89, QED 0.63
Compound (SMILES): C#CCO[C@@H]1[C@H](C)[C@@H](COC(=O)c2ccc(S(=O)(=O)F)cc2)O[C@H]1n1nc(-c2ccc(C)cc2)c2c(N)ncnc21
InChIKey: VCIZYTQJDGPPDJ-CLQHIKNWSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of Abl (unknown origin) incubated for 1 hr by ADP-Glo assay
Measurement: IC50 = 182 nM (pChEMBL 6.739999771118164)
Descriptors: MW 579.61, ALogP 3.45, HBA 11, HBD 1, PSA 148.52, QED 0.19
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(-c3nc4ccc(C(F)(F)F)cc4n3[C@H](C)c3ccc(F)cc3)cc2)cc1
InChIKey: KPMTUCCYXWPTAN-HXUWFJFHSA-N
Target: Nuclear receptor ROR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35398
Assay: Inverse agonist activity at human GAL4-fused RORalpha LBD transfected in 293T cell measured after 24 hrs by dual luciferase assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 609.65, ALogP 7.45, HBA 5, HBD 1, PSA 81.06, QED 0.19
Compound (SMILES): CCOC(=O)c1ncc2[nH]c3ccccc3c2c1COC
InChIKey: IUHKSTINHDUYRO-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16445
Assay: Binding affinity to human recombinant GABAA alpha6 receptor assessed as inhibition constant incubated for 1 hrs by liquid scintillation counting analysis
Measurement: Ki = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 284.31, ALogP 3.04, HBA 4, HBD 1, PSA 64.21, QED 0.75
Compound (SMILES): CNCCNCc1cccc(-c2nc(Nc3ccccc3)c(C)c(-c3c(C)noc3C)n2)c1
InChIKey: DVIUIRPCVXVFSX-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR22
Assay: Inhibition of PRMT8 (unknown origin) incubated for 15 mins measured after 60 min by AlphaLISA assay
Measurement: IC50 = 920 nM (pChEMBL 6.039999961853027)
Descriptors: MW 442.57, ALogP 4.78, HBA 7, HBD 3, PSA 87.9, QED 0.32
Compound (SMILES): CCCCNNC(=O)c1ccc(F)cc1
InChIKey: YRLLWXIGAGZKFP-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 10880 nM (pChEMBL 4.960000038146973)
Descriptors: MW 210.25, ALogP 1.86, HBA 2, HBD 2, PSA 41.13, QED 0.58
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(CC)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: FDTGYJGRULJHQZ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: HER2 Exon 20 YVMA Insertion Mutation: A compound's ability in selectively inhibiting Her2 exon 20 YVMA insertion mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with Her2 Exon20 YVMA insertions. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR exon 20 insertions YVMA (A775_G776ins YVMA), was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR exon 20 insertions. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR Exon20 virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing Her2 Exon20 YVMA insertions (named Ba/F3-Her2 Exon20 YVMA) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-Her2 Exon20 YVMA cells seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega; this assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives). Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 599.74, ALogP 5.56, HBA 10, HBD 2, PSA 113.85, QED 0.15
Compound (SMILES): O=C(CNc1cc(Cl)cc(Cl)c1)N1CC[C@H]2CCN(c3ncnc4[nH]ccc34)[C@H]2C1
InChIKey: ZJKAMIGVAPQVOU-UGSOOPFHSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using tolbutamide as substrate measured after 15 mins in the presence of NADPH by LC/MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 445.35, ALogP 3.8, HBA 5, HBD 2, PSA 77.15, QED 0.64
Compound (SMILES): O=C([O-])CNC(=O)c1ccc(S(=O)(=O)N2CCC(c3ccc(Cl)cc3)CC2)cn1.[K+]
InChIKey: DJLPNUNUNPABGA-UHFFFAOYSA-M
Target: Ubiquitin carboxyl-terminal hydrolase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6I4
Assay: Binding affinity to biotinylated USP3 zinc finger ubiquitin binding domain (1 to 131 residues) (unknown origin) expressed in Escherichia coli incubated for 120 secs by Biolayer Interferometry assay
Measurement: Kd = 100000 nM (pChEMBL 4)
Descriptors: MW 437.91, ALogP 2.12, HBA 5, HBD 2, PSA 116.67, QED 0.71
Compound (SMILES): O=C1N[C@H]2C[C@@H](C2)OCc2cccc(n2)Nc2cc([nH]n2)[C@H]2CC[C@H](C2)O1
InChIKey: LAQCQSKKZIRXFW-MHEUCROKSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK3beta (unknown origin) assessed as inhibition of substrate peptide phosphorylation using eIF4E-binding protein 1 as peptide substrate incubated for 1 hr in presence of ATP by Lance Ultra HTRF assay
Measurement: IC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 369.43, ALogP 2.97, HBA 6, HBD 3, PSA 101.16, QED 0.66
Compound (SMILES): O=c1[nH]c(/C=C/c2cccc(F)c2)nc2ccccc12
InChIKey: ZFGIVIZXCYOWBK-CMDGGOBGSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3KCG (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 266.27, ALogP 3.23, HBA 2, HBD 1, PSA 45.75, QED 0.77
Compound (SMILES): NCCCC[C@H](NC(=O)C(NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)C(c1ccccc1)c1ccccc1)C(N)=O
InChIKey: GGAKLYWEFZCVIT-NIEMNNIISA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate assessed as reduction in substrate hydroxylation incubated for 5 mins in presence of beta-NADPH measured by LC-MS/MS analysis
Measurement: IC50 = 8800 nM (pChEMBL 5.059999942779541)
Descriptors: MW 1439.82
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2ccc(-c3c(C)nn(C)c3C#N)cc2N2C[C@@H](N)C[C@H]2CO)n1
InChIKey: YXFNNHJWPFANTQ-OALUTQOASA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Inhibition of STK4 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 318 nM (pChEMBL 6.5)
Descriptors: MW 556.6, ALogP 3.02, HBA 10, HBD 3, PSA 155.21, QED 0.31
Compound (SMILES): Cc1cc(OC(F)F)ccc1NC(=O)c1cc(C(=O)NCc2ccc(F)cc2)c(F)cc1Cl
InChIKey: NFAGOVIQVGGRKR-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Agonist activity at human PPARalpha expressed in CHO cells co-expressing GAL4-NHR-LBD assessed as transcriptional activation preincubated for 6 hrs followed by luciferin addition by luminescence method
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 480.85, ALogP 5.71, HBA 3, HBD 2, PSA 67.43, QED 0.43
Compound (SMILES): Fc1ccc(Cl)c(Sc2n[nH]c3ncc(-c4cnn(C5CCNCC5)c4)cc23)c1Cl
InChIKey: FCLVBOUURHAHBG-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-MET (unknown origin)
Measurement: IC50 = 14.6 nM (pChEMBL 7.840000152587891)
Descriptors: MW 463.37, ALogP 5.34, HBA 6, HBD 2, PSA 71.42, QED 0.4
Compound (SMILES): O=C(O)c1cc(-c2ccc(/C=N/Nc3nc4nonc4nc3Nc3ccccc3)o2)ccc1Cl
InChIKey: BKOFAWBQRGSHGD-BHGWPJFGSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition SRC (unknown origin)
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 475.85, ALogP 4.81, HBA 10, HBD 3, PSA 151.56, QED 0.22
Compound (SMILES): O=C(O)c1ccc2c(c1)nc(NCc1ccccc1)c1ncccc12
InChIKey: VBKHXXPYOSWXSA-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (SINGLE PROTEIN), Homo sapiens
UniProt: O60331
Assay: Inhibition of wild type human PIP5K1C in presence of ATP by radiometric kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 329.36, ALogP 4.09, HBA 4, HBD 2, PSA 75.11, QED 0.55