lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C)CC1CN(C(=O)CCc2ccccc2)CCC1(O)c1cccc(O)c1
InChIKey: ZZHZGTPZEPFTHC-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human KOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 648.9 nM (pChEMBL 6.190000057220459)
Descriptors: MW 382.5, ALogP 2.62, HBA 4, HBD 2, PSA 64.01, QED 0.81
Compound (SMILES): O=C(Nc1cnccc1Cl)c1ccnc(NC(=O)C2CC2)c1
InChIKey: TVOFBUNUDWXBSZ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GST tagged GSK-3beta (unknown origin) incubated for 1 hrs by HTRF assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 316.75, ALogP 2.73, HBA 4, HBD 2, PSA 83.98, QED 0.91
Compound (SMILES): CC(C)n1cc(C(N)=O)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: BDEDFXSJTOMMGU-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR L858R mutant assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 peptide as substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 466.53, ALogP 2.45, HBA 10, HBD 2, PSA 150.68, QED 0.42
Compound (SMILES): C[C@@H]1[C@H](Nc2ncnc3[nH]ccc23)CCCN1C(=O)CNc1cc(Cl)cc(Cl)c1
InChIKey: HORBTILEDZCTEX-SJKOYZFVSA-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 433.34, ALogP 4.17, HBA 5, HBD 3, PSA 85.94, QED 0.56
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(OCCCN5CCNC(=O)C5)cc4CC[C@H]3[C@@H]1CC[C@@H]2N1CCCC1
InChIKey: RIRRGFQDQGSWPP-GVGNIZHQSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of N-alpha-[methyl-3H]-methylhistamine dihydrochloride from recombinant human histamine H3 receptor expressed in CHO-K1 cells assessed as inhibition constant incubated for 30 mins by liquid scintillation analysis
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 465.68, ALogP 4.21, HBA 4, HBD 1, PSA 44.81, QED 0.64
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4ccc(Oc5ccccc5)c(O)c4)nn32)CC1
InChIKey: VWYWHQKPHALPKU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Inhibition of TEC (unknown origin) preincubated for 1 hrs followed by substrate addition and measured after 1 hrs in the presence of ATP at Km concentration by TR-FRET assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 487.56, ALogP 3.93, HBA 7, HBD 3, PSA 122.71, QED 0.45
Compound (SMILES): NC(=O)[C@H](CO)NC(=O)/C=N/OCc1ccc(S(N)(=O)=O)cc1
InChIKey: FQLZUPPGCDINMG-XSFFOXFNSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 assessed as inhibition constant
Measurement: Ki = 346 nM (pChEMBL 6.460000038146973)
Descriptors: MW 344.35, ALogP -2.2, HBA 7, HBD 4, PSA 174.17, QED 0.31
Compound (SMILES): CC(C)n1nc(C(=O)NC2CC3CCC(C2)N3CC2(O)CCOCC2)c2ccccc21.O=C(O)C(O)C(O)C(=O)O
InChIKey: RSZFVLCTKYYCEA-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 426.56, ALogP 2.88, HBA 6, HBD 2, PSA 79.62, QED 0.77
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2ccccc2)CCC1(O)c1cccc(O)c1
InChIKey: VKEFHVLSPCSJQG-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human KOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 169.1 nM (pChEMBL 6.769999980926514)
Descriptors: MW 368.48, ALogP 2.23, HBA 4, HBD 2, PSA 64.01, QED 0.85
Compound (SMILES): C[C@H]1CN(S(=O)(=O)c2ccc3c(c2)CCO3)C[C@@H]1C(=O)Nc1ccc2scnc2c1
InChIKey: WGQMHSUZVPFXPO-GUYCJALGSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Antagonist activity at human muscarinic M1 receptor expressed in CHO cells in the presence of acetylcholine by calcium mobilisation assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 443.55, ALogP 3.13, HBA 6, HBD 1, PSA 88.6, QED 0.67
Compound (SMILES): COC(=O)[C@]1(c2ccc(Cl)cc2)C[C@@H]1CN1CC[C@]2(C)c3cc(O)ccc3C[C@@H]1[C@@H]2C
InChIKey: SSKRLXLHQCKGKE-NZTYDEPOSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-Diprenorphine from DOR receptor (unknown origin) assessed as inhibition constant
Measurement: Ki > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 439.98, ALogP 4.7, HBA 4, HBD 1, PSA 49.77, QED 0.7
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4c(=O)n(C5C=CCCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: JJEGWIJBJXWVDU-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 540.67, ALogP 3.98, HBA 10, HBD 2, PSA 104.34, QED 0.35
Compound (SMILES): CC(=O)N1CCC(c2cc3c(N[C@H](C)c4cc(N)cc(C(F)(F)F)c4)nc(C)nc3n(C)c2=O)CC1
InChIKey: CANNEHAOSZSHJR-CYBMUJFWSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 502.54, ALogP 4.14, HBA 7, HBD 2, PSA 106.14, QED 0.52
Compound (SMILES): Fc1ccc(CN2CCCC23CCN(Cc2cc4ccc(Cl)cc4[nH]2)C3)cc1F
InChIKey: RHKLNFPODGBPGC-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 268 nM (pChEMBL 6.570000171661377)
Descriptors: MW 415.92, ALogP 5.34, HBA 2, HBD 1, PSA 22.27, QED 0.62
Compound (SMILES): CC(=O)Nc1ccc(-c2ccnc(NCc3ccc(OCCCCCC(=O)NO)cc3)n2)cc1
InChIKey: SMSJBIDKIQNFIK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin)
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 463.54, ALogP 4.16, HBA 7, HBD 4, PSA 125.47, QED 0.18
Compound (SMILES): CC[Si](C#Cc1cccc2c1OC(C(F)(F)F)C([N+](=O)[O-])=C2)(CC)CC
InChIKey: IHIRLDQLFPQTJC-UHFFFAOYSA-N
Target: Alpha-2B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P18089
Assay: Binding affinity to adrenergic alpha 2b receptor (unknown origin)
Measurement: Ki = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 383.44
Compound (SMILES): CN(C)c1ccc(-c2cn(-c3ccc(S(=O)(=O)NC(Cc4ccccc4)C(=O)NO)cc3)nn2)cc1
InChIKey: FPRZOPYGOUMBED-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of MMP2 (unknown origin)
Measurement: IC50 = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 506.59, ALogP 2.4, HBA 8, HBD 3, PSA 129.45, QED 0.23
Compound (SMILES): O=C(CCCCCC(=O)N(Cc1ccc(Br)s1)c1ccc(OCCN2CCOCC2)cc1)NO
InChIKey: JEMNZPZBYORGTE-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 1.14 nM (pChEMBL 8.9399995803833)
Descriptors: MW 554.51, ALogP 4.21, HBA 7, HBD 2, PSA 91.34, QED 0.22
Compound (SMILES): C=CC(=O)N1CCCC(n2nc3c(=O)[nH]nc(N)c3c2-c2oc3ccc(C)cc3c2C)C1
InChIKey: KEAWMUNHKYSQEN-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) using Poly (Glu,Tyr) 4:1 as substrate incubated for 60 mins in presence of ATP by ELISA analysis
Measurement: IC50 = 155.2 nM (pChEMBL 6.809999942779541)
Descriptors: MW 432.48, ALogP 3.08, HBA 7, HBD 2, PSA 123.04, QED 0.48
Compound (SMILES): Cc1ccc2nc(Nc3cnn(C4CCN(C)CC4)c3)nc(OC3(C)CC3)c2n1
InChIKey: QRRAWPZSLULASL-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) in presence of 600 uM ATP
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 393.5, ALogP 3.47, HBA 8, HBD 1, PSA 80.99, QED 0.71
Compound (SMILES): CCCCNNC(=O)c1ccccc1
InChIKey: ZYBWZQIGNAKZJX-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 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 192.26, ALogP 1.72, HBA 2, HBD 2, PSA 41.13, QED 0.55
Compound (SMILES): O=C1/C(=C/c2ccc(O)cc2O)Cc2ccccc21
InChIKey: RBDZAUOXRXNMMO-XYOKQWHBSA-N
Target: Tyrosinase (SINGLE PROTEIN), Agaricus bisporus
UniProt: O42713
Assay: Inhibition of mushroom tyrosinase using L-dopa as substrate incubated for 30 mins by spectrophotometric analysis
Measurement: IC50 = 1390 nM (pChEMBL 5.860000133514404)
Descriptors: MW 252.27, ALogP 2.92, HBA 3, HBD 2, PSA 57.53, QED 0.77
Compound (SMILES): O=C(Nc1ccc(F)cc1-c1ccc(F)c(Cl)c1)OC1CCNCC1
InChIKey: AVALEAUYDHXJQZ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M3 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 366.8, ALogP 4.59, HBA 3, HBD 2, PSA 50.36, QED 0.84
Compound (SMILES): O=C(c1ccco1)N1CCCc2cc(NS(=O)(=O)c3ccc([N+](=O)[O-])cc3)ccc21
InChIKey: GHNMQBBTNORDTI-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Modulation of glucocorticoid receptor (unknown origin) transfected in human HeLa cells assessed as transrepression by measuring inhibition of PMA-induced AP-1 signalling incubated for 18 hrs by dual-luciferase reporter based assay
Measurement: IC50 = 4270 nM (pChEMBL 5.369999885559082)
Descriptors: MW 427.44, ALogP 3.58, HBA 6, HBD 1, PSA 122.76, QED 0.49
Compound (SMILES): C=CC(=O)Nc1ccccc1C1CCNc2c(C(N)=O)c(-c3cc(OC)c(C4CC4)c(OC)c3)nn21
InChIKey: NCEZXFYYHDEYFJ-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 = 20.3 nM (pChEMBL 7.690000057220459)
Descriptors: MW 487.56, ALogP 4.07, HBA 7, HBD 3, PSA 120.5, QED 0.41
Compound (SMILES): CCCNC(=O)CCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.Cl
InChIKey: WYJVWUPKXCVBCP-VZYDHVRKSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Antagonist activity against recombinant human adrenergic alpha1B receptor expressed in CHO cells incubated for 30 mins by FLIPR analysis
Measurement: Ki = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 481.04, ALogP 4.41, HBA 5, HBD 1, PSA 67.23, QED 0.47
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2ccc(F)cc2)CCC1(O)c1cccc(O)c1
InChIKey: GRWAVFOCRMSSTA-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at MOR (unknown origin) expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding measured after 60 mins by liquid scintillation counting analysis
Measurement: EC50 = 6.4 nM (pChEMBL 8.1899995803833)
Descriptors: MW 386.47, ALogP 2.37, HBA 4, HBD 2, PSA 64.01, QED 0.83
Compound (SMILES): Br.Br.CCCN(CCc1cc(O)c(CCN(CCC)[C@H]2CCc3c(O)cccc3C2)cc1O)[C@H]1CCc2c(O)cccc2C1
InChIKey: JHMPBPUPTSSMTN-ARDORAJISA-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 = 1.53 nM (pChEMBL 8.8100004196167)
Descriptors: MW 572.79, ALogP 6.13, HBA 6, HBD 4, PSA 87.4, QED 0.2
Compound (SMILES): CC(=O)N1CCC(n2cc(Nc3nc(OC4CCOCC4)c4nc(C)ccc4n3)cn2)CC1
InChIKey: VMYCKCWYEIGQOV-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin) in presence of 400 uM ATP
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 451.53, ALogP 3.01, HBA 9, HBD 1, PSA 107.29, QED 0.63
Compound (SMILES): Cc1ccc(-c2ccc3c(C)n[nH]c3c2)c2c1[C@H](N(C)C(=O)c1ncccc1C(F)F)CCC2
InChIKey: ZGVMLURVURNUQI-HSZRJFAPSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of his-tagged c-MET D1228V mutant (1050 to 1346 residues) (unknown origin) by ADP-glo assay
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 460.53, ALogP 6.33, HBA 3, HBD 1, PSA 61.88, QED 0.39
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)CN)CSSC[C@@H]2NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]3CCCN3C(=O)[C@@H]3CSSC[C@@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CSSC[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)CNC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N3)NC(=O)[C@H]([C@@H](C)CC)NC2=O
InChIKey: LONNDNYWMXEIQJ-PHIYFGQBSA-N
Target: Suppressor of tumorigenicity 14 protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y6
Assay: Inhibition of recombinant human matriptase using Boc-QAR-MCA as substrate
Measurement: Ki = 1430 nM (pChEMBL 5.840000152587891)
Descriptors: MW 3290.81
Compound (SMILES): CC(C)CN(c1ccc(C(=O)O)c(O)c1)S(=O)(=O)c1ccc(Oc2ccccc2)cc1
InChIKey: JHTQTAIFWLPTNR-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: fluorescence polarization competition assay (FPCA): Molecular modeling and SILCS functional group affinity mapping (FragMaps) of the Mcl-1 binding site indicated that the carboxylic acid of designed molecule 3a (FIG. 1C) would occupy an energetically favorable region, associated with a salt bridge interaction with R263 of the Mcl-1 binding site, while the ring of the naphthyl core would bind in the p3 pocket demarcated by a favorable non-polar FragMap. The aniline was directed into the hydrophobic p2 pocket, which is also demarcated by a nonpolar FragMap. With the molecular modeling data in hand, compound 3a was then synthesized according to Scheme 1-2.Briefly, commercially available 1-hydroxy-2-naphthoic acid (4) was regioselectively 4-chlorosulfonylated to yield 5, which was isolated by pouring over ice and used without further purification. Sulfonyl chloride 5 was next reacted with 4-bromoaniline to furnish the target molecule 3a in excellent overall yield (83%). Evaluation of 3a in a fluorescence polarization competition assay (FPCA) indicated that it disrupted the Mcl-1-Bak-BH3 PPI with an IC50 of 10.9 μM, corresponding to a Ki of 2.76 μM. Given the ability of 3a to inhibit Mcl-1, a structure-activity relationship (SAR) study was developed, the results of which are presented in the tables below.
Measurement: Ki = 17996 nM (pChEMBL 4.75)
Descriptors: MW 441.51, ALogP 4.73, HBA 5, HBD 2, PSA 104.14, QED 0.52
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCN(C)Cc1cccc(O)c1
InChIKey: OHBHEABPPWROKD-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 4890 nM (pChEMBL 5.309999942779541)
Descriptors: MW 408.54, ALogP 5.25, HBA 5, HBD 1, PSA 54.7, QED 0.33
Compound (SMILES): Cc1cc(NC(=O)CN2CCC3(CCCN(Cc4ccc(F)c(F)c4)C3)C2)ccc1F
InChIKey: WLNCDWOGRLAGPA-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]N-methylspiperone from D3 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki = 376 nM (pChEMBL 6.420000076293945)
Descriptors: MW 431.5, ALogP 4.34, HBA 3, HBD 1, PSA 35.58, QED 0.77
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c(C5CCCC5)c(OC)c4)nn32)CC1
InChIKey: WDZZTNVBOLILQA-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 = 49.4 nM (pChEMBL 7.309999942779541)
Descriptors: MW 507.64, ALogP 4.11, HBA 7, HBD 2, PSA 111.71, QED 0.55
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3ccc(F)cc3OC)cc2)nc2cnccc12)C(N)=O
InChIKey: VDPQATJURMCMDU-OAQYLSRUSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 assessed as reduction in PI4,5P2 production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 2 mM ATP by HTRF assay
Measurement: IC50 = 2440 nM (pChEMBL 5.610000133514404)
Descriptors: MW 455.49, ALogP 4.66, HBA 6, HBD 2, PSA 113.92, QED 0.42
Compound (SMILES): O=C(/C=C/c1ccc(N2CC(=O)N3C(Cc4c([nH]c5ccccc45)C3c3ccc4c(c3)OCO4)C2=O)cc1)NO
InChIKey: DOKZSZOGYUKABQ-KPKJPENVSA-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 536.54, ALogP 3.3, HBA 6, HBD 3, PSA 124.2, QED 0.21
Compound (SMILES): CC(C)=CCc1ccc(O)c([C@@]2(O)c3c(O)cc(C)cc3C(=O)C2(C)C)c1O
InChIKey: JIIKZACQDAPJRU-QHCPKHFHSA-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 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 382.46, ALogP 4.08, HBA 5, HBD 4, PSA 97.99, QED 0.6
Compound (SMILES): CCOC(=O)CCCc1ccc(N/C=N/O)cc1
InChIKey: HJEKWTVRPSQJRV-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human recombinant CYP3A4 using Luciferin-IPA as substrate incubated for 30 mins in presence of NADPH by luminescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 250.3, ALogP 2.4, HBA 4, HBD 2, PSA 70.92, QED 0.26
Compound (SMILES): CCS[C@H]1CC[C@@H](N(C)CC(=O)Nc2ccc(C)c(C)c2)C1
InChIKey: GBDWBLMTSCWWNJ-SJORKVTESA-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 = 10 nM (pChEMBL 8)
Descriptors: MW 320.5, ALogP 3.85, HBA 3, HBD 1, PSA 32.34, QED 0.86
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCN(/C(=N/O)c3ccc([N+](=O)[O-])cc3)CC2)cc1
InChIKey: OJIHELHNRHXZIF-HTXNQAPBSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 405.44, ALogP 1.2, HBA 7, HBD 2, PSA 142.37, QED 0.26
Compound (SMILES): Cc1onc(-c2ccccc2)c1C(=O)NCCCCCNC(=O)C(C)S
InChIKey: IMIDYBQMXWFUIG-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 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 375.49, ALogP 2.98, HBA 5, HBD 3, PSA 84.23, QED 0.46
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCCCCCN(C)Cc1cccc(O)c1
InChIKey: QMEQQKSEEYBQTB-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 478.68, ALogP 7.2, HBA 5, HBD 1, PSA 54.7, QED 0.16
Compound (SMILES): Cc1cc(CC(=O)O)cc(CN2CCN(c3nc4ccc(C(F)(F)F)cc4s3)CC2)c1
InChIKey: PIFQMAQSAUVRLP-UHFFFAOYSA-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 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 449.5, ALogP 4.57, HBA 5, HBD 1, PSA 56.67, QED 0.62
Compound (SMILES): O=C(N1CCN2CCC1CC2)n1nc(-c2ccc(F)cc2)c2c1COCC2
InChIKey: CDUXPGVKEOGWKB-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 370.43, ALogP 2.51, HBA 5, HBD 0, PSA 50.6, QED 0.77
Compound (SMILES): Cc1cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc2n(C2CCCC2)c1=O
InChIKey: KQERORPUPHLRGX-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 = 39.1 nM (pChEMBL 7.409999847412109)
Descriptors: MW 405.52, ALogP 2.05, HBA 7, HBD 1, PSA 97.19, QED 0.84
Compound (SMILES): O=C1C[C@@H](Cc2cnc[nH]2)CO1
InChIKey: URBYRAOLXWIITQ-ZCFIWIBFSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Partial agonist activity at N-terminal FLAG tagged/C-terminal NanoLuc tagged human muscarinic M4 receptor expressed in HEK293T cells using furimazine as substrate assessed as receptor activation preincubated with substrate for 1 min followed by compound addition and measured for 6 mins 27 sec by NanoBRET assay
Measurement: EC50 = 7413.1 nM (pChEMBL 5.130000114440918)
Descriptors: MW 166.18, ALogP 0.52, HBA 3, HBD 1, PSA 54.98, QED 0.65
Compound (SMILES): CC1Cc2ccccc2N1C(=O)NCCCCN(C)[C@H]1Cc2cccc3[nH]c(=O)n(c23)C1
InChIKey: CXVWRWOFYFBNKU-OZBJMMHXSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at human D2 receptor assessed as beta arrestin-2 recruitment
Measurement: EC50 = 839.5 nM (pChEMBL 6.079999923706055)
Descriptors: MW 433.56, ALogP 3.13, HBA 4, HBD 2, PSA 73.37, QED 0.59
Compound (SMILES): CC[C@@H]1CN(Cc2cc(C)cc(CC(=O)O)c2)CCN1c1nc2ccc(C(F)(F)F)cc2s1
InChIKey: ZBKXSRSXIGZPCY-LJQANCHMSA-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 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 477.55, ALogP 5.35, HBA 5, HBD 1, PSA 56.67, QED 0.52
Compound (SMILES): CC(NC(=O)C1CCCC1)C(=O)Nc1nnc(Cc2ccc([N+](=O)[O-])cc2)s1
InChIKey: LSKCLOVTKNMGQQ-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 21 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UK80
Assay: Binding affinity to recombinant human N-terminal His6-tagged USP21 (209 to 563 residues) expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by SPR analysis
Measurement: Kd = 7.87 nM (pChEMBL 8.100000381469727)
Descriptors: MW 403.46, ALogP 2.67, HBA 7, HBD 2, PSA 127.12, QED 0.54
Compound (SMILES): N#Cc1cccc(-c2ccc3ncc(-c4cccc(F)c4)c(N4CCC(N)CC4)c3c2)c1O
InChIKey: FXYNHVQSAANDCY-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 438.51, ALogP 5.21, HBA 5, HBD 2, PSA 86.17, QED 0.46
Compound (SMILES): CN(CC[C@@H]1CC[C@H](CNC(=O)c2cc3ccccc3[nH]2)C1)[C@@H]1Cc2cccc3[nH]c(=O)n(c23)C1
InChIKey: UWXLBLFCZDJRKI-CNNODRBYSA-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 = 196 nM (pChEMBL 6.710000038146973)
Descriptors: MW 471.61, ALogP 3.9, HBA 4, HBD 3, PSA 85.92, QED 0.38
Compound (SMILES): Cc1cc(Cn2nc(Br)cc2Cl)cc(=O)n1C[C@H]1C[C@@H]1C#N
InChIKey: SKDDVCIQXLNTPS-VXGBXAGGSA-N
Target: Glutamate receptor ionotropic, NMDA 2C (SINGLE PROTEIN), Homo sapiens
UniProt: Q14957
Assay: Positive allosteric modulator activity at GluN2C NMDA receptor (unknown origin) expressed in CHO cells co-expressing GluN1a in the presence of L-glutamate and glycine by Ca2+ influx assay
Measurement: EC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 381.66, ALogP 2.98, HBA 5, HBD 0, PSA 63.61, QED 0.82
Compound (SMILES): Cc1nc2cc(NC(=O)c3cc4sc(N5CCC(C(=O)N(C)C)CC5)nc4s3)ccc2o1
InChIKey: AIMDOKRPWXBXFC-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 469.59, ALogP 4.36, HBA 8, HBD 1, PSA 91.57, QED 0.48
Compound (SMILES): Cc1nc(N2CCN(C(=O)c3ccco3)CC2)c2c3c(sc2n1)CC(C)(C)CC3
InChIKey: NJZNNXDITCGBSK-UHFFFAOYSA-N
Target: G-protein coupled receptor 55 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2T6
Assay: Inverse agonist activity at human GPR55 expressed in HEK293 cells coexpressing serum response element assessed as reduction in MAPK/ERK signalling pathway by measuring SRE response incubated for 5 hrs in serum-free medium by luciferin based bioluminescence analysis
Measurement: EC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 410.54, ALogP 4.07, HBA 6, HBD 0, PSA 62.47, QED 0.64
Compound (SMILES): Cc1ccc(Sc2cc(C(=O)N3Cc4ccccc4C3)ccc2O)cc1C
InChIKey: AXEQZLWHIYQNKM-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P08238
Assay: Binding affinity to HSP90beta (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 375.49, ALogP 5.32, HBA 3, HBD 1, PSA 40.54, QED 0.67
Compound (SMILES): COCC(=O)NCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.O=C(O)C(F)(F)F
InChIKey: PPWSKWDOMYLZPK-VEIFNGETSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Antagonist activity against recombinant human adrenergic alpha1B receptor expressed in CHO cells incubated for 30 mins by FLIPR analysis
Measurement: Ki = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 468.99, ALogP 2.87, HBA 6, HBD 1, PSA 76.46, QED 0.52
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(OCCCCN5CCCC5)cc4CC[C@H]3[C@@H]1CC[C@@H]2N1CCCC1
InChIKey: BBPNHCYTOLQTJQ-ZNOUKXQUSA-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 = 24.8 nM (pChEMBL 7.610000133514404)
Descriptors: MW 450.71, ALogP 6.26, HBA 3, HBD 0, PSA 15.71, QED 0.46
Compound (SMILES): CC[C@](C)(O)C#Cc1cc2c(cn1)cnn2-c1ccnc(N)n1
InChIKey: WZLQQYUWMGFXDE-INIZCTEOSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of NIK (unknown origin)
Measurement: IC50 = 675 nM (pChEMBL 6.170000076293945)
Descriptors: MW 308.35, ALogP 1.31, HBA 7, HBD 2, PSA 102.74, QED 0.69
Compound (SMILES): COc1cc(C(=O)[N-]S(=O)(=O)c2ccc(-n3nc(C(F)(F)F)cc3-c3ccc(C)cc3)cc2)ccc1[O-].[Na+].[Na+]
InChIKey: NQHQSRIKOQLGPT-UHFFFAOYSA-L
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Inhibition of COX1 (unknown origin)
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 531.51, ALogP 4.7, HBA 7, HBD 2, PSA 110.52, QED 0.37
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2cc(F)c(F)cc2F)CCC1(O)c1cccc(O)c1
InChIKey: JMDFENKDWRFUQU-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at MOR (unknown origin) expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding measured after 60 mins by liquid scintillation counting analysis
Measurement: EC50 = 57.1 nM (pChEMBL 7.239999771118164)
Descriptors: MW 422.45, ALogP 2.65, HBA 4, HBD 2, PSA 64.01, QED 0.73
Compound (SMILES): Cc1onc(-c2ccccc2)c1/C=C/c1ccc(CNC(=O)C(C)(C)S)cc1
InChIKey: IQEYSQCGFQVIBG-BUHFOSPRSA-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 392.52, ALogP 5.15, HBA 4, HBD 2, PSA 55.13, QED 0.57
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3F)nc2-c2ccc3[nH]ncc3c2)n1
InChIKey: FFCNMKMMYJYENY-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 416.44, ALogP 5.21, HBA 4, HBD 3, PSA 82.28, QED 0.37
Compound (SMILES): Cc1cc(CC(=O)O)cc(CN2CCN(c3nc4ccc(C(F)(F)F)cc4s3)[C@@H](C)C2)c1
InChIKey: HVXGLCUTIOCPRK-HNNXBMFYSA-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 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 463.53, ALogP 4.96, HBA 5, HBD 1, PSA 56.67, QED 0.58
Compound (SMILES): CN1CCN(C(=O)CCCN2CCN(c3cccc(Cl)c3Cl)CC2)C(C(=O)NCc2ccccc2)C1
InChIKey: QEYPINFPGIXPDO-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 = 0.2138 nM (pChEMBL 9.670000076293945)
Descriptors: MW 532.52, ALogP 3.35, HBA 5, HBD 1, PSA 59.13, QED 0.57
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC3CCC3)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: LDZREOHPCZNERK-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 597.72, ALogP 5.22, HBA 10, HBD 2, PSA 113.85, QED 0.17
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c5ccsc5c4)nn32)CC1
InChIKey: GOLVRUHMODBSGJ-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 = 63.3 nM (pChEMBL 7.199999809265137)
Descriptors: MW 465.58, ALogP 3.65, HBA 7, HBD 2, PSA 102.48, QED 0.56
Compound (SMILES): CCNc1cc(Nc2ccc(C(=O)N3CCC(N4CCOCC4)CC3)cc2OC)nc2[nH]cc(C(F)(F)F)c12
InChIKey: FKRHOHUJMCOWDZ-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant human CLK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 40.5 nM (pChEMBL 7.389999866485596)
Descriptors: MW 546.59, ALogP 4.7, HBA 7, HBD 3, PSA 94.75, QED 0.4
Compound (SMILES): C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1n1ccc2cnc3[nH]cc(C#N)c3c21
InChIKey: PFZVRMSUBHGEID-DOMZBBRYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human JAK2 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 346.39, ALogP 2.71, HBA 5, HBD 1, PSA 101.5, QED 0.77
Compound (SMILES): O=C1C(Nc2cccc(OC(F)F)c2)CCN1c1ccc(-c2n[nH]c(=O)c3ccccc23)cc1
InChIKey: JAGCQTZNUQROMH-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of ROCK2 (unknown origin)
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 462.46, ALogP 4.41, HBA 5, HBD 2, PSA 87.32, QED 0.44
Compound (SMILES): CN1CCN(c2ccc(Nc3nccc(-c4ccc([N+](=O)[O-])cc4)n3)cc2C(F)(F)F)CC1
InChIKey: PCZLHHXHFHLORK-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 = 180 nM (pChEMBL 6.75)
Descriptors: MW 458.44, ALogP 4.57, HBA 7, HBD 1, PSA 87.43, QED 0.44
Compound (SMILES): CCCOc1ccc2c(c1)OC1(CCN(c3ccc(S(N)(=O)=O)cc3[N+](=O)[O-])CC1)CC2=O
InChIKey: XCYWVZRLAGYWAB-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant
Measurement: Ki = 4152.5 nM (pChEMBL 5.380000114440918)
Descriptors: MW 475.52, ALogP 3.04, HBA 8, HBD 1, PSA 142.07, QED 0.5
Compound (SMILES): Nc1cc(F)cc(-c2ccc(O)c(C(=O)C3CCc4ccccc43)c2)c1O
InChIKey: VSEVSZZZZPLJHX-UHFFFAOYSA-N
Target: Peptidyl-prolyl cis-trans isomerase C (SINGLE PROTEIN), Homo sapiens
UniProt: P45877
Assay: Inhibition of CypC (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 363.39, ALogP 4.4, HBA 4, HBD 3, PSA 83.55, QED 0.37
Compound (SMILES): O=C(NO)c1ccc(NC(=O)[C@@H](NC(=O)c2cccc(Br)c2)c2ccccc2)cc1
InChIKey: GKDSLRGHAAFGPK-IBGZPJMESA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human HDAC6 using fluorogenic as substrate measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 195.8 nM (pChEMBL 6.710000038146973)
Descriptors: MW 468.31, ALogP 3.68, HBA 4, HBD 4, PSA 107.53, QED 0.33
Compound (SMILES): CC(C)c1c(Oc2ccc(CN)cc2Cl)ccc2c1B(O)OC2
InChIKey: ZIIWGJMMDJWIKB-UHFFFAOYSA-N
Target: Protein kinase C alpha type (SINGLE PROTEIN), Homo sapiens
UniProt: P17252
Assay: Competition Binding Assay: Phosphorylation of activity of ROCK1 and ROCK2 and those of other kinases, AKT1, GRK2, PKA, PKCa and RSK1 were performed by Reaction Biology (Malvern, Pa.) (Ma et al., 2008) The ROCK1 enzyme tested was GST[1-535] ROCK1 (Genbank, NP 005397), ROCK2 was GST[5-554] (Genbank, 3327051). For the kinase assay buffers contained 20 mM Hepes, 10 mM MgCl2, 2 mM DTT, 0.02 mg/mL BSA, 0.1% DMSO, 1 mM EGTA, 0.02% Brij-35, 10 uM ATP, [γP33]-ATP and for ROCK enzymes, 20 uM long S6-peptide (32 amino acids length). Appropriate substrates and activation was applied for the other kinases tested. Each enzyme was preincubated with test compound for 15 min., and the reaction started by addition of ATP. Samples were incubated at room temperature for 120 min, and applied to P81 ion exchange paper and washed extensively; the radioactive content of the filters were determined.
Measurement: IC50 = 10.8 nM (pChEMBL 7.96999979019165)
Descriptors: MW 331.61
Compound (SMILES): CN(CC[C@@H]1CC[C@@H](CNC(=O)c2cc3ccccc3[nH]2)C1)[C@@H]1Cc2cccc3[nH]c(=O)n(c23)C1
InChIKey: UWXLBLFCZDJRKI-NNMXDRDESA-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 = 415 nM (pChEMBL 6.380000114440918)
Descriptors: MW 471.61, ALogP 3.9, HBA 4, HBD 3, PSA 85.92, QED 0.38
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(N[C@H](CC)C(N)=O)c2C#N)cc1
InChIKey: OZMTYRUNCOMFJT-JOCHJYFZSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 assessed as reduction in PI4,5P2 production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 2 mM ATP by HTRF assay
Measurement: IC50 = 11200 nM (pChEMBL 4.949999809265137)
Descriptors: MW 451.53, ALogP 4.91, HBA 6, HBD 2, PSA 113.92, QED 0.39
Compound (SMILES): CC(C)n1nc(N2CCOCC2)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: XXHWNVXLWADDQU-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M double mutant autophosphorylation in human NCI-H1975 cells harboring harboring EGFR L858R/T790M double mutant preincubated for 60 mins followed by EGF stimulation and measured after 8 mins by SULFO-TAG based electrochemiluminescent assay
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 509.6, ALogP 2.59, HBA 12, HBD 1, PSA 132.95, QED 0.4
Compound (SMILES): COCCOc1ccc2c(c1)OC1(CCN(c3ccc(S(N)(=O)=O)cc3[N+](=O)[O-])CC1)CC2=O
InChIKey: AKUMOHXAIHNVPB-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human CA9 assessed as inhibition constant
Measurement: Ki = 45.4 nM (pChEMBL 7.340000152587891)
Descriptors: MW 491.52, ALogP 2.27, HBA 9, HBD 1, PSA 151.3, QED 0.35
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2N=C(c3ccc(F)cc3)CC2c2ccc(F)cc2)cc1
InChIKey: NRUWIFGSWLNHJQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12
Measurement: Ki = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 441.46, ALogP 3.6, HBA 4, HBD 1, PSA 92.83, QED 0.67
Compound (SMILES): Cc1cn(-c2ccccc2)c2ccc(C(=O)NS(C)(=O)=O)cc12
InChIKey: FIXIITTZIGLTCR-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.5/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 79000 nM (pChEMBL 4.099999904632568)
Descriptors: MW 328.39, ALogP 2.63, HBA 4, HBD 1, PSA 68.17, QED 0.8
Compound (SMILES): CC(O)(CCCc1ccccc1)c1cc(C(=O)N2Cc3ccc(F)cc3C2)ccc1O
InChIKey: CRJBRLBNXARYEQ-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P08238
Assay: Binding affinity to HSP90beta (unknown origin) assessed as dissociation constant by fluorescence polarization assay
Measurement: Kd = 3790 nM (pChEMBL 5.420000076293945)
Descriptors: MW 419.5, ALogP 4.92, HBA 3, HBD 2, PSA 60.77, QED 0.6
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3ccccc3OC)cc2)nc2cnccc12)C(N)=O
InChIKey: BKGMBRCBFNCTSH-OAQYLSRUSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 assessed as reduction in PI4,5P2 production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 2 mM ATP by HTRF assay
Measurement: IC50 = 2430 nM (pChEMBL 5.610000133514404)
Descriptors: MW 437.5, ALogP 4.52, HBA 6, HBD 2, PSA 113.92, QED 0.44
Compound (SMILES): CN1/C(=C/C=C/C=C/C2=[N+](CCCCCC(=O)NCCCCCCN3CCC(COC(=O)Nc4ccc(F)cc4-c4ccc(F)c(Cl)c4)CC3)c3ccccc3C2(C)C)C(C)(C)c2ccccc21
InChIKey: MMUOGZOUFNQXMP-UHFFFAOYSA-O
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 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 945.66, ALogP 13.28, HBA 5, HBD 2, PSA 76.92, QED 0.05
Compound (SMILES): CN(CCc1ccccc1)S(=O)(=O)c1cccc(/C=C/C(=O)NO)c1
InChIKey: VLCXJLKMJMKPJC-ZHACJKMWSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of HDAC4 (unknown origin)
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 360.44, ALogP 2.07, HBA 4, HBD 2, PSA 86.71, QED 0.45
Compound (SMILES): N#Cc1ccccc1N1CCN(C[C@H](O)COC[C@H](Cc2ccccc2)NC(=O)C2CCN(C(=O)OCc3ccccc3)CC2)CC1
InChIKey: FCORXOBTLFNQOU-HEVIKAOCSA-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): Cc1cc(-c2ccc3nc(C4CCOCC4)n(CCOC(F)(F)F)c3c2)cn(C)c1=O
InChIKey: KPWWFNXRLAAREN-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity BRD4 (unknown origin) assessed as dissociation constant
Measurement: Kd = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 435.45, ALogP 4.14, HBA 6, HBD 0, PSA 58.28, QED 0.6
Compound (SMILES): Nc1cccc(F)c1CN(CCC1CCS(=O)(=O)CC1)C(=O)c1cc(C(F)(F)F)n[nH]1
InChIKey: GASMZUDGPKMAEI-UHFFFAOYSA-N
Target: Pyruvate kinase PKM (SINGLE PROTEIN), Homo sapiens
UniProt: P14618
Assay: Activation of PKM2 (unknown origin) in presence of HSP90 inhibitor
Measurement: ED50 = 36.45 nM (pChEMBL 7.440000057220459)
Descriptors: MW 462.47, ALogP 3.01, HBA 5, HBD 2, PSA 109.15, QED 0.51
Compound (SMILES): O=C(NO)c1ccc(NC(=O)[C@@H](NC(=O)c2ccc3ccccc3c2)c2ccccc2)cc1
InChIKey: VKUKPEYLIALRQI-QHCPKHFHSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human HDAC6 using fluorogenic as substrate measured after 30 mins by fluorescence based analysis
Measurement: IC50 = 375.8 nM (pChEMBL 6.420000076293945)
Descriptors: MW 439.47, ALogP 4.07, HBA 4, HBD 4, PSA 107.53, QED 0.27
Compound (SMILES): N#Cc1nc2c(nc1N1CCC(F)(F)CC1)-c1ccccc1C2=O
InChIKey: AECQDHMORDWPQD-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P40818
Assay: Inhibition of USP8 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 326.31, ALogP 2.8, HBA 5, HBD 0, PSA 69.88, QED 0.69
Compound (SMILES): CC(C)=CCc1ccc(O)c(C(=O)c2c(O)cc(C)cc2C2=C(c3c(O)ccc(CC=C(C)C)c3O)c3c(O)cc(C)cc3C2=O)c1O
InChIKey: ZEQJCGYKVUDWOK-UHFFFAOYSA-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 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 646.74, ALogP 7.94, HBA 8, HBD 6, PSA 155.52, QED 0.08
Compound (SMILES): CC(C)n1cc(C(N)=O)c2cnc(Nc3ccnc(-c4cnn(S(=O)(=O)C5CC5)c4)n3)cc21
InChIKey: BDEDFXSJTOMMGU-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR del (746 to 750) mutant assessed as apparent inhibition constant using Fl-EEPLYWSFPAKKK-CONH2 as substrate preincubated for 30 mins followed by addition of substrate and measured after 30 mins by Morrison plot analysis
Measurement: Ki = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 466.53, ALogP 2.45, HBA 10, HBD 2, PSA 150.68, QED 0.42
Compound (SMILES): C[C@@H]1[C@H](Nc2ncnc3[nH]ccc23)CCCN1C(=O)CNc1cc(Cl)cc(Cl)c1
InChIKey: HORBTILEDZCTEX-SJKOYZFVSA-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 433.34, ALogP 4.17, HBA 5, HBD 3, PSA 85.94, QED 0.56
Compound (SMILES): C[C@]12CC[C@@H]3c4ccc(OCCCN5CCNC(=O)C5)cc4CC[C@H]3[C@@H]1CC[C@@H]2N1CCCC1
InChIKey: RIRRGFQDQGSWPP-GVGNIZHQSA-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 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 465.68, ALogP 4.21, HBA 4, HBD 1, PSA 44.81, QED 0.64
Compound (SMILES): NC(=O)[C@H](CO)NC(=O)/C=N/OCc1ccc(S(N)(=O)=O)cc1
InChIKey: FQLZUPPGCDINMG-XSFFOXFNSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibition constant
Measurement: Ki = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 344.35, ALogP -2.2, HBA 7, HBD 4, PSA 174.17, QED 0.31
Compound (SMILES): C[C@H]1CN(S(=O)(=O)c2ccc3c(c2)CCO3)C[C@@H]1C(=O)Nc1ccc2scnc2c1
InChIKey: WGQMHSUZVPFXPO-GUYCJALGSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Antagonist activity at human muscarinic M4 receptor expressed in CHO cells in the presence of acetylcholine by calcium mobilisation assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 443.55, ALogP 3.13, HBA 6, HBD 1, PSA 88.6, QED 0.67