lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)N[C@@H](C)CO
InChIKey: POMBIFQUJUHXAV-AWEZNQCLSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: In Vitro Kinase Assay Inhibition of ALK1/2/3/4/5/6 Kinases: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle. IC50 values were generated from activity values performed at multiple concentrations.
Measurement: IC50 = 10400 nM (pChEMBL 4.980000019073486)
Descriptors: MW 442.92, ALogP 4.91, HBA 5, HBD 3, PSA 87.14, QED 0.48
Compound (SMILES): CCc1cc(C#N)cc2c(NCc3ccc(OC)c(Cl)c3)c(COCCF)cnc12
InChIKey: DCVUFHLTJMRFBO-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of PDE5A (unknown origin)
Measurement: IC50 = 33.4 nM (pChEMBL 7.480000019073486)
Descriptors: MW 427.91, ALogP 5.43, HBA 5, HBD 1, PSA 67.17, QED 0.46
Compound (SMILES): COc1ccc(Nc2ncnc3c2ccn3-c2ccc(C)c(C)c2)cc1Cl
InChIKey: DZIHITUUUPJMOQ-UHFFFAOYSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of GST-fused human recombinant PI5P4Kalpha expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 378.86, ALogP 5.44, HBA 5, HBD 1, PSA 51.97, QED 0.51
Compound (SMILES): COc1cccc(C2(O)CCN(C(=O)C3(c4ccccc4)CCC3)CC2CN(C)C)c1
InChIKey: CNNKSWQUFACVPO-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 = 205 nM (pChEMBL 6.690000057220459)
Descriptors: MW 422.57, ALogP 3.41, HBA 4, HBD 1, PSA 53.01, QED 0.78
Compound (SMILES): Cc1cc(Oc2ccc(S(=O)(=O)N3CCCc4cc(C(=O)O)ccc43)cc2)cc(C)c1Cl
InChIKey: KQLSOYSLAVZLOS-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Binding affinity to MCL-1 (unknown origin) assessed as inhibition constant
Measurement: Ki = 2730 nM (pChEMBL 5.559999942779541)
Descriptors: MW 471.96, ALogP 5.59, HBA 4, HBD 1, PSA 83.91, QED 0.52
Compound (SMILES): O=C(Nc1cnccc1-c1ccccc1F)c1ccnc(NC(=O)C2CC2)c1
InChIKey: NCJPNQVCPACJMH-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 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 376.39, ALogP 3.88, HBA 4, HBD 2, PSA 83.98, QED 0.71
Compound (SMILES): Cc1c(Cl)cccc1NC(=O)CN1CCC2(CCCN2Cc2ccc(F)c(F)c2)C1
InChIKey: QXQOZVSPURYOAI-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 = 1704 nM (pChEMBL 5.769999980926514)
Descriptors: MW 433.93, ALogP 4.61, HBA 3, HBD 1, PSA 35.58, QED 0.75
Compound (SMILES): CP(C)(=O)c1ccccc1-c1ccc(N2CC3(CC3)[C@@H](NC(=O)Nc3ccc(Cl)cc3F)C2=O)c(F)c1F
InChIKey: DPHVSMCTVGYRRO-DEOSSOPVSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: Agonist activity at human FPR1 expressed in CHO cells assessed as cAMP level incubated for 1.5 hr by HTRF assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 561.93, ALogP 5.99, HBA 3, HBD 2, PSA 78.51, QED 0.38
Compound (SMILES): COc1ccc2c(c1)OC1(CCN(c3ccc(S(N)(=O)=O)cc3[N+](=O)[O-])CC1)CC2=O
InChIKey: JHNNUPWYLCFGLP-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to human CA7 assessed as inhibition constant
Measurement: Ki = 0.39 nM (pChEMBL 9.40999984741211)
Descriptors: MW 447.47, ALogP 2.26, HBA 8, HBD 1, PSA 142.07, QED 0.56
Compound (SMILES): CN1CCN(C(=O)C(C)(C)c2ccc(C(=O)Cc3cn4cc(-c5ccncc5)ccc4n3)cc2)CC1
InChIKey: AOLMNCAPVYTEHC-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of recombinant human CLK1 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 106.8 nM (pChEMBL 6.96999979019165)
Descriptors: MW 481.6, ALogP 3.87, HBA 6, HBD 0, PSA 70.81, QED 0.39
Compound (SMILES): CCCOc1ccc(NC(=O)C(C)(C)c2csc(NS(=O)(=O)C3CC3)n2)cc1
InChIKey: BOEWQRNBSGZWMC-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 = 235 nM (pChEMBL 6.630000114440918)
Descriptors: MW 423.56, ALogP 3.75, HBA 6, HBD 2, PSA 97.39, QED 0.64
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(C[C@H](C)C(=O)O)c2C#N)cc1
InChIKey: ZOCYJBFYLLNYQK-KRWDZBQOSA-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 cells assessed as reduction in ADP production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 250 uM ATP by ADP-Glo luminescent assay
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 437.5, ALogP 5.5, HBA 5, HBD 1, PSA 96.1, QED 0.41
Compound (SMILES): CC1(C)[C@@H]2[C@@H](C(=O)N[C@H](C=O)C[C@@H]3CCNC3=O)N(C(=O)COc3ccc(Cl)cc3Cl)C[C@@H]21
InChIKey: BDFIPRXCQILSGM-ZUHDPNGNSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of eGFP-fused SARS-CoV-2 main protease transfected in HEK293T/17 cells incubated for 3 days by flow cytometry analysis
Measurement: EC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 496.39, ALogP 2.07, HBA 5, HBD 2, PSA 104.81, QED 0.54
Compound (SMILES): NS(=O)(=O)c1ccc(-n2cc(COC(=O)c3ccc4c(c3)C(=O)N(c3ccc(Cl)cc3)C4=O)nn2)cc1
InChIKey: CLELLOLWPKLTHX-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human transmembrane carbonic anhydrase 4 using 4-nitrophenyl acetate as substrate assessed as inhibition constant by spectrophotometric analysis
Measurement: Ki = 29.94 nM (pChEMBL 7.519999980926514)
Descriptors: MW 537.94, ALogP 2.73, HBA 9, HBD 1, PSA 154.55, QED 0.29
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(-c4nc5ccccc5[nH]4)c3c2)Cn2nnnc2N1C
InChIKey: XULTUONTNLFTDL-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human wild type LRRK2 expressed in HEK293 cells assessed as reduction in pSer935 phosphorylation incubated for 2 hrs by HTRF analysis
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 426.44, ALogP 2.46, HBA 8, HBD 3, PSA 133.3, QED 0.4
Compound (SMILES): CC(C)n1nc(-c2nnc(C3CCN(CC4(O)CCCC4)CC3)o2)c2ccccc21.O=C(O)C(=O)O
InChIKey: IWULMJQXAMPTDP-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 2 mins in presence of NADPH regenerating system by LC-MS/MS analysis
Measurement: IC50 > 45000 nM (pChEMBL 4.3470001220703125)
Descriptors: MW 409.53, ALogP 4.15, HBA 7, HBD 1, PSA 80.21, QED 0.68
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(-c3nc4ccc(C)cc4n3[C@@H](C)c3ccc(C)cc3)cc2)cc1
InChIKey: IGPRUALXJOEVNF-DEOSSOPVSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Inverse agonist activity at human GAL4-fused LXRalpha LBD transfected in 293T cell measured after 24 hrs by dual luciferase assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 551.71, ALogP 6.9, HBA 5, HBD 1, PSA 81.06, QED 0.23
Compound (SMILES): Cc1ccc(-c2cc(-c3ccc(S(=O)(=O)N[C@H](C(=O)O)C(C)C)cc3)no2)s1
InChIKey: NNCVCMDUQDAWGY-SFHVURJKSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of MMP8 (unknown origin)
Measurement: IC50 = 0.567 nM (pChEMBL 9.25)
Descriptors: MW 420.51, ALogP 3.77, HBA 6, HBD 2, PSA 109.5, QED 0.6
Compound (SMILES): C[C@@H]1CN(CCOc2cc(CC(=O)O)ccc2Cl)CCN1c1nc2ccc(Cl)cc2s1
InChIKey: DORQQPRGWXDMDY-CQSZACIVSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at Gal4-fused human PPAR-gamma 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 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 480.42, ALogP 4.82, HBA 6, HBD 1, PSA 65.9, QED 0.52
Compound (SMILES): C/C=C1\CN2CC[C@@]34c5ccccc5N(Cc5ccccc5)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: GHNOYQGNCIPRAH-OIAMUCEYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from kappa opioid receptor (unknown origin) assessed as inhibition constant incubated for 180 mins by competitive radioligand binding assay
Measurement: Ki = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 442.56, ALogP 3.88, HBA 5, HBD 0, PSA 42.01, QED 0.53
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(N[C@H](CC)C(=O)NS(=O)(=O)C3CC3)c2C#N)cc1
InChIKey: VTAXIHMISZQRAG-RUZDIDTESA-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 cells assessed as reduction in ADP production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 250 uM ATP by ADP-Glo luminescent assay
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 555.66, ALogP 5.03, HBA 8, HBD 2, PSA 134.07, QED 0.28
Compound (SMILES): CCCOc1c(CCC)cc(-c2ccccc2C(=O)O)cc1NC(=O)Nc1ccc(C)cc1
InChIKey: UYODUNYIATWXJO-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG
Measurement: IC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 446.55, ALogP 6.75, HBA 3, HBD 3, PSA 87.66, QED 0.34
Compound (SMILES): O=C(Cn1c(CCCN2CCN(c3cccc(Cl)c3Cl)CC2)nc2ccccc21)NCc1ccccc1
InChIKey: RCOOYZUDBHDXOZ-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Partial agonist activity at human D4 receptor expressed in HEK293T cells assessed as inhibition of forskolin-induced cAMP production incubated for 1 hr by HTRF analysis
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 536.51, ALogP 5.41, HBA 5, HBD 1, PSA 53.4, QED 0.31
Compound (SMILES): N[C@@H]1c2ccccc2CC12CCN(c1nc3nc(Sc4ccncc4Cl)cnc3[nH]1)CC2
InChIKey: ZGZATUCGLSWXHC-LJQANCHMSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of E-4031 from hERG by fluorescence polarization assay
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 464, ALogP 4.4, HBA 7, HBD 2, PSA 96.61, QED 0.46
Compound (SMILES): O=C(Nc1cnccc1-c1ccc(F)cc1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: AMINIFOLNFYOOD-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15418
Assay: Inhibition of RSK1 (unknown origin) by Ambit kinase assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 376.39, ALogP 3.88, HBA 4, HBD 2, PSA 83.98, QED 0.71
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c5ccoc5c4)nn32)CC1
InChIKey: RRDIEPDENZRYJK-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 = 241.4 nM (pChEMBL 6.619999885559082)
Descriptors: MW 449.51, ALogP 3.19, HBA 7, HBD 2, PSA 115.62, QED 0.58
Compound (SMILES): COc1ccc2sc(-c3cncc(NC(C)=O)c3)nc2c1
InChIKey: JLUXIHDOQQZMIZ-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of recombinant human CLK1 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 572.4 nM (pChEMBL 6.239999771118164)
Descriptors: MW 299.36, ALogP 3.33, HBA 5, HBD 1, PSA 64.11, QED 0.81
Compound (SMILES): COc1ccc(OC)c(-n2nnc(C(=O)Nc3cc(N)cc(C(C)(C)C)c3)c2C)c1
InChIKey: XQDOBDMVBRMCDS-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Antagonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition in rifampicin-induced receptor activation incubated for 24 hrs by luminescence based analysis
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 409.49, ALogP 3.72, HBA 7, HBD 2, PSA 104.29, QED 0.62
Compound (SMILES): COCCOc1cc(F)c2c(c1)CC[C@@H]2Nc1nc2nc(O[C@@H]3CO[C@H]4[C@@H]3OC[C@H]4O)[nH]c2cc1Cl
InChIKey: RWALQNUYYICDCM-UMBWAWJWSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using mephenytoin as substrate
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 520.95, ALogP 2.78, HBA 9, HBD 3, PSA 119.98, QED 0.38
Compound (SMILES): O=C(OCCO)c1ccc(NS(=O)(=O)c2cccc(-c3cc(F)ccc3O)c2)cc1O
InChIKey: QRDFCYMUXHUTCS-UHFFFAOYSA-N
Target: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16875
Assay: Inhibition of PFKFB3 in human PANC-1 cells assessed as reduction in Fructose-2,6-Bisphosphate production
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 447.44, ALogP 2.85, HBA 7, HBD 4, PSA 133.16, QED 0.41
Compound (SMILES): CC(=O)N1c2ccc(NC(=O)OCC(C)(C)C)nc2C2(CCCCC2)C1(C)C
InChIKey: FTSSQIDVPOPJTQ-UHFFFAOYSA-N
Target: Follicle-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P23945
Assay: Antagonist activity at human FSHR expressed in HEK293 cells assessed as reduction in cAMP production incubated for 2 hrs by Eu-cAMP tracer based TR-FRET assay
Measurement: IC50 = 8240 nM (pChEMBL 5.079999923706055)
Descriptors: MW 387.52, ALogP 5.02, HBA 4, HBD 1, PSA 71.53, QED 0.77
Compound (SMILES): CCOC(=O)N1C[C@@H]2C[C@H]1CN2c1nc(SC)cc(-c2cnc(N)c(OC(F)F)n2)n1
InChIKey: WQQYNNJZQBRUAR-UWVGGRQHSA-N
Target: Mitogen-activated protein kinase kinase kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12852
Assay: Inhibition of human DLK expressed in HEK cells assessed as reduction in phospho-c-Jun level preincubated for 45 mins followed by doxycycline stimulation and measured after 24 hrs by MSD ELISA
Measurement: EC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 453.48, ALogP 2.26, HBA 10, HBD 1, PSA 119.59, QED 0.52
Compound (SMILES): Nc1cc(Oc2ccc3c(C(=O)Nc4cccc(C(F)(F)F)c4)cccc3c2)ncn1
InChIKey: IOYGAWXBNPFOKF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Mus musculus
UniProt: P35918
Assay: Inhibition of mouse recombinant GST-fused VEGFR2 kinase domain expressed in baculovirus expression system using poly-Glu-Tyr (4:1) as substrate measured after 10 mins in presence of gamma-[33P]-ATP by scintillation counting analysis
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 424.38, ALogP 5.28, HBA 5, HBD 2, PSA 90.13, QED 0.47
Compound (SMILES): C=CC(=O)N1CCC([C@@H]2CCNc3c(C(N)=O)c(-c4cc(OC)c(C5CC5)c(OC)c4)nn32)CC1
InChIKey: NVDXHXCRQAOJQR-SFHVURJKSA-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 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 479.58, ALogP 3.32, HBA 7, HBD 2, PSA 111.71, QED 0.59
Compound (SMILES): CCCCCOc1ccc(C(C)(C)C)cc1NC(=O)c1nnn(-c2cc(OC)ccc2OC)c1C
InChIKey: VPKRKNQWMOOMMJ-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Antagonist activity at human PXR in human HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter assessed as inhibition in rifampicin-induced receptor activation incubated for 24 hrs by luminescence based analysis
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 480.61, ALogP 5.71, HBA 7, HBD 1, PSA 87.5, QED 0.37
Compound (SMILES): C[C@@H]1CCN(C(=O)C(C)(C)C#N)C[C@@H]1n1c(=O)[nH]c2cnc3[nH]ccc3c21
InChIKey: GYUXLQMAEBVNBP-RISCZKNCSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 kinase domain using biotin-Lyn-substrate-2 as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 366.43, ALogP 2.17, HBA 5, HBD 2, PSA 110.57, QED 0.72
Compound (SMILES): O=C(O)c1ccc2c(c1)nc(NCc1ccccc1)c1ncncc12
InChIKey: HEVVNKYNJCSHFA-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Inhibition of wild type human CK2alpha in presence of ATP by radiometric kinase assay
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 330.35, ALogP 3.49, HBA 5, HBD 2, PSA 88, QED 0.56
Compound (SMILES): O=C(NCCN1CCOCC1)Nc1nc2ccc(Sc3nnc4ccc(-c5ccccc5)nn34)cc2s1
InChIKey: WTVCPJCTIVZLQJ-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of human MET M1250T mutant incubated for 1 hrs by ELISA assay
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 532.66, ALogP 4.01, HBA 10, HBD 2, PSA 109.57, QED 0.32
Compound (SMILES): CCCCNNC(=O)c1ccc(Cl)cc1
InChIKey: SOFXANVWFFBJSR-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 = 3750 nM (pChEMBL 5.429999828338623)
Descriptors: MW 226.71, ALogP 2.37, HBA 2, HBD 2, PSA 41.13, QED 0.6
Compound (SMILES): NS(=O)(=O)c1ccc(-n2cc(COC(=O)c3ccc4c(c3)C(=O)N(Cc3ccc5c(c3)OCO5)C4=O)nn2)cc1
InChIKey: QNJQVLYQHWMMHP-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 = 23.9 nM (pChEMBL 7.619999885559082)
Descriptors: MW 561.53, ALogP 1.8, HBA 11, HBD 1, PSA 173.01, QED 0.26
Compound (SMILES): Cc1cn(-c2cccc(F)c2)c2ccc(C(=O)NS(=O)(=O)C3CC3)cc12
InChIKey: LLHOCWOJQNGDRO-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 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 372.42, ALogP 3.3, HBA 4, HBD 1, PSA 68.17, QED 0.76
Compound (SMILES): Cc1cc(F)cc(-c2cnc3ccc(-c4cccc(C#N)c4O)cc3c2N2CCC(N)CC2)c1
InChIKey: UJWVFOZDAGJLCH-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 452.53, ALogP 5.52, HBA 5, HBD 2, PSA 86.17, QED 0.43
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(-c4ccncc4)c3c2)[C@@H](C)n2nnnc2N1C
InChIKey: AGBHROMNNPQXGK-GFCCVEGCSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant expressed in HEK293 cells assessed as reduction in pSer935 phosphorylation incubated for 2 hrs by HTRF analysis
Measurement: IC50 = 14.7 nM (pChEMBL 7.829999923706055)
Descriptors: MW 401.43, ALogP 2.53, HBA 8, HBD 2, PSA 117.51, QED 0.54
Compound (SMILES): CN1C[C@@H]2CC[C@H](C1=O)N2c1ncc2[nH]nc(-c3cnn(C4CCC4)c3)c2n1
InChIKey: OXJWXQVCCWDQJS-DZGCQCFKSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of recombinant human FGFR2 (400 to 821 residues) using biotin-EQEDEPEGDYFEWLE-amide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 1 hr in presence of ATP by HTRF assay
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 378.44, ALogP 1.75, HBA 7, HBD 1, PSA 95.83, QED 0.75
Compound (SMILES): O=C(c1cccnc1Oc1cc(Cl)ccc1Cl)N1CCN(C2COC2)c2ccccc21
InChIKey: KPXRVFTXTHPVCY-UHFFFAOYSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU6
Assay: Agonist activity at TGR5 (unknown origin) expressed in HEK293 cells
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 456.33, ALogP 5.05, HBA 5, HBD 0, PSA 54.9, QED 0.55
Compound (SMILES): CNCc1ccc(-c2cc3cc(F)cc(C(N)=O)c3o2)cc1.Cl
InChIKey: GPFWTAVHQKERKY-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Affinity Biochemical interaction: (Inhibition of enzymatic activity, D+ used as substrate for PAR formation) EUB0002633aCl PARP2
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 298.32, ALogP 3.06, HBA 3, HBD 2, PSA 68.26, QED 0.78
Compound (SMILES): Cc1ccc(NC(=O)Nc2cc(-c3ccccc3-c3nn[nH]n3)ccc2OC(C(C)C)C(C)C)cc1
InChIKey: CAKPSXBSEIXTPN-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 484.6, ALogP 6.55, HBA 5, HBD 3, PSA 104.82, QED 0.26
Compound (SMILES): N#Cc1ccc(N2C(=O)c3ccc(C(=O)OCc4cn(-c5ccc(S(N)(=O)=O)cc5)nn4)cc3C2=O)cc1
InChIKey: WNAIWAZVDQQDMK-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 = 28.56 nM (pChEMBL 7.539999961853027)
Descriptors: MW 528.51, ALogP 1.94, HBA 10, HBD 1, PSA 178.34, QED 0.29
Compound (SMILES): Cc1[nH]nc2ccc(-c3cncc(OC[C@@H](N)CC(C)C)c3)cc12
InChIKey: CEDLXWRFEZCVEU-INIZCTEOSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of CLK2 (unknown origin) by ADP-Glo assay
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 324.43, ALogP 3.69, HBA 4, HBD 2, PSA 76.82, QED 0.72
Compound (SMILES): CC[C@@H]1C(=O)OC[C@@H]1Cc1c[n+](CCCCCC[N+](C)(C)CC(C)(C)CN2C(=O)c3cccc4cccc(c34)C2=O)cn1C.[Br-].[Br-]
InChIKey: KMUQEAFREKKPCG-XJZDMYKTSA-L
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 = 1318.26 nM (pChEMBL 5.880000114440918)
Descriptors: MW 602.82, ALogP 5.17, HBA 5, HBD 0, PSA 72.49, QED 0.08
Compound (SMILES): COc1cccc(/C=C/C(=O)NC[C@H](Cc2ccccc2)NS(=O)(=O)c2ccc(Br)cc2)c1
InChIKey: YOLVZOJWYFHBDZ-NCSHYYEOSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 529.46, ALogP 4.18, HBA 4, HBD 2, PSA 84.5, QED 0.39
Compound (SMILES): CN(C)C[C@H]1CN(C(=O)Cc2cc(F)c(F)cc2F)CC[C@]1(O)c1cccc(O)c1
InChIKey: JMDFENKDWRFUQU-AOMKIAJQSA-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 = 109.8 nM (pChEMBL 6.960000038146973)
Descriptors: MW 422.45, ALogP 2.65, HBA 4, HBD 2, PSA 64.01, QED 0.73
Compound (SMILES): NOCc1ccc(S(N)(=O)=O)cc1
InChIKey: DQGRYZFBJINKGB-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibition constant
Measurement: Ki = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 202.24, ALogP -0.28, HBA 4, HBD 2, PSA 95.41, QED 0.66
Compound (SMILES): CC(C)(C)NS(=O)(=O)c1cccc(NC(=O)c2ncc(NS(C)(=O)=O)nc2N2CCC3(CC2)CC3)n1
InChIKey: QEJRJBGBBKFHPC-UHFFFAOYSA-N
Target: Kinesin-like protein KIF18A (SINGLE PROTEIN), Mus musculus
UniProt: Q91WD7
Assay: Inhibition of recombinant His-tagged mouse KIF18A expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 537.67, ALogP 1.95, HBA 9, HBD 3, PSA 163.35, QED 0.48
Compound (SMILES): CC(=O)NC1CSCc2cc3cc(c2)CSC(C(N)=O)NC(=O)C(CC(C)C)NC(=O)C(CC(=O)O)NC(=O)C(CCC(N)=O)NC(=O)C(Cc2c[nH]cn2)NCC(C)NC(=O)C(CSC3)NC(=O)C(CCCNC(=N)N)NC(=O)C(Cc2ccc(O)cc2)NC(=O)C2CCN2C(=O)C(Cc2ccccc2)NC(=O)C(CO)NC1=O
InChIKey: NATBJNOLJXJRBB-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition of human fXIa using Boc-FSR-AMC as substrate assessed as inhibition constant by fluorescence plate reader analysis
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1655.95
Compound (SMILES): C[C@H]1CN(C)CCN1c1cc(NC(=O)Cn2cc(-c3cc(F)c(O)c(C(N)=O)c3)c3c(=O)n(C)cnc32)c(Cl)cn1
InChIKey: MPTZCPVBMHMFLN-AWEZNQCLSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Surface Plasmon Resonance (SPR) Assay: SPR studies were performed using a Biacore™ T200 instrument (GE Health Sciences Inc.). The BCL6 BTB protein used in the FP assay was biotinylated using the site specific biotinylating enzyme BirA, and then cleaved with TEV protease to produce the BCL6 BTB domain (biotin-thrombin-BCL6 amino acids 1-129; 17 kd) that were use in SPR. This protein was stably captured (1000RU) to streptavidin coupled SA chips (BR-1005-31, GE Health Sciences Inc.) according to the manufacture's protocol. Compounds were dissolved in 100% DMSO at 10 mM and 2-fold serial dilutions were done in 100% DMSO. For SPR analysis the serially titrated compounds were diluted 1/20 into buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.05% Tween-20, 3 mM EDTA) giving a final concentration of 5% DMSO. The Biacore flow rate was set at 100 ul/min. For KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 seconds. Curve fitting and KD calculations were done with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 15.5 nM (pChEMBL 7.809999942779541)
Descriptors: MW 583.02, ALogP 2.17, HBA 10, HBD 3, PSA 151.61, QED 0.31
Compound (SMILES): CNC(=O)c1cc(CNC(=O)c2ccc3c(c2)c(COc2ccc4[nH]ccc4c2)cn3S(C)(=O)=O)cc(=O)[nH]1
InChIKey: VRQGZVGFCPUFBJ-UHFFFAOYSA-N
Target: Sentrin-specific protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0U3
Assay: Inhibition of human recombinant His6 tagged SENP1 catalytic domain expressed in Escherichia coli BL21 (DE3) using SUMO3-AMC as substrate incubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 = 27000 nM (pChEMBL 4.570000171661377)
Descriptors: MW 547.59, ALogP 2.49, HBA 7, HBD 4, PSA 155.15, QED 0.23
Compound (SMILES): CN1CCC[C@H](N(c2cc(C#CC(C)(C)C)sc2C(=O)O)C(=O)[C@H]2CC[C@H](C)CC2)C1=O
InChIKey: MGEVBIDQMYTWFL-LNLFQRSKSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of human PXR expressed in human DPX2 co-expressing luciferase reporter gene incubated for 24 hrs by luciferase assay
Measurement: EC50 = 17300 nM (pChEMBL 4.760000228881836)
Descriptors: MW 458.62, ALogP 4.62, HBA 4, HBD 1, PSA 77.92, QED 0.67
Compound (SMILES): Cc1ccc(-[n+]2ccc3c4ccccc4n(C)c3c2)cc1
InChIKey: TYLORRYICLSBDT-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE (unknown origin) incubated for 40 mins by Ellman's method
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 273.36, ALogP 3.92, HBA 1, HBD 0, PSA 8.81, QED 0.46
Compound (SMILES): C=CC(=O)N1CC[C@@H](n2nc(C#Cc3cc(OC)cc(OC)c3)c3c(N)ncnc32)C1
InChIKey: KEIPNCCJPRMIAX-OAHLLOKOSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) by ELISA
Measurement: IC50 = 3.05 nM (pChEMBL 8.520000457763672)
Descriptors: MW 418.46, ALogP 1.78, HBA 8, HBD 1, PSA 108.39, QED 0.51
Compound (SMILES): Cc1c(NC(=O)NCCN2C(=O)S/C(=C\c3ccc([N+](=O)[O-])cc3)C2=O)c(=O)n(-c2ccccc2)n1C
InChIKey: FSZALWOMKKPDGK-RGEXLXHISA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) by ELISA assay
Measurement: IC50 = 144 nM (pChEMBL 6.840000152587891)
Descriptors: MW 522.54, ALogP 3.25, HBA 9, HBD 2, PSA 148.58, QED 0.27
Compound (SMILES): Cc1n[nH]c2cc(N(CC3CCCC3)C(=O)NCCCn3cncc3C)ccc12
InChIKey: XGQBWUPWPHJCNV-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase (SINGLE PROTEIN), Mus musculus
UniProt: Q9CYK2
Assay: Inhibition of mouse glutaminyl cyclase
Measurement: IC50 = 18.2 nM (pChEMBL 7.739999771118164)
Descriptors: MW 394.52, ALogP 4.17, HBA 4, HBD 2, PSA 78.84, QED 0.59
Compound (SMILES): CC(C)C(O)c1nc(-c2cnc(N)c(C(F)(F)F)c2)cn1C12CC(N3CCOCC3)(C1)C2
InChIKey: BURDQUKVCPYGRG-UHFFFAOYSA-N
Target: Protein delta homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P80370
Assay: Inhibition of DLK (unknown origin)
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 451.49, ALogP 3.2, HBA 7, HBD 2, PSA 89.43, QED 0.73
Compound (SMILES): O=C1C2=C(CCN(Cc3ccccc3)C2)N2CCN=C2N1Cc1ccc(C(F)(F)F)cc1
InChIKey: DFULPGUTXZTYKA-UHFFFAOYSA-N
Target: ATP-dependent Clp protease proteolytic subunit (SINGLE PROTEIN), Escherichia coli (strain K12)
UniProt: P0A6G7
Assay: Agonist activity at Escherichia coli ClpP using alpha-casein as substrate assessed as substrate hydrolysis preincubated for 15 mins followed by substrate addition and measured after 2 hrs by SDS-PAGE analysis
Measurement: EC50 = 3970 nM (pChEMBL 5.400000095367432)
Descriptors: MW 440.47, ALogP 3.88, HBA 4, HBD 0, PSA 39.15, QED 0.72
Compound (SMILES): COc1ccc(Nc2ncnc3c2ccn3-c2ccc(C)c(C)c2)cn1
InChIKey: VPRWXJPWZQZZGN-UHFFFAOYSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of PI5P4Kalpha in human HEK293 cells incubated for 60 mins by luminescence based analysis
Measurement: IC50 > 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 345.41, ALogP 4.18, HBA 6, HBD 1, PSA 64.86, QED 0.6
Compound (SMILES): Cc1cc(-c2cnn(C)c2)cc([C@@H]2CCN(C(=O)c3cc(C(C)C)n[nH]3)C2)n1
InChIKey: LNMSTPSCCSYARO-OAHLLOKOSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: KDM5 Enzyme Assay: Full length KDM5A enzyme was expressed and purified inhouse. Biotin-H3K4me3 peptide was purchased from New England Biolabs. HTRF reagents (containing Eu-labeled H3K4me1-2 antibody, and streptavidin-XL665) were purchased from Cis-Bio International. Plates were read on an Envision multi-label plate reader (Perkin Elmer).The HTRF assay mixture contained 2 nM full length KDM5A enzyme, 100 nM H3K4Me3 peptide substrate, 1 uM 2-OG, 100 uM Fe2+, 500 uM ascorbate. 50 mM HEPES pH 7.0 buffer, 0.01% Triton-X 100, 2 mM DTT, 0.25% DMSO at a final volume of 10 uL.The enzyme reaction was carried out at room temperature in black Proxiplate 384-Plus plate (Corning. Costar) within 30 minutes, in the presence of varying concentration of a test compound. At the end of enzyme reaction, 5 uL of 1 mM EDTA were added to quench the reaction and then the detection reagents (5 uL) were added to give final concentrations of 0.5 nM Eu-labeled H3K4me1-2 antibody, and 50 nM streptavidin-XL665. The plates were incubated at room temperature for 60 minutes and then read in the Envision plate reader. The readouts were transformed into % inhibition, and IC50 value of a test compounds was generated by using four parameters curve fitting (Model 205 in XLFIT5, iDBS).
Measurement: IC50 = 0.84 nM (pChEMBL 9.079999923706055)
Descriptors: MW 378.48, ALogP 3.27, HBA 5, HBD 1, PSA 79.7, QED 0.76
Compound (SMILES): CN(C)CC1CN(C(=O)CCc2cccc(C(F)(F)F)c2)CCC1(O)c1cccc(O)c1
InChIKey: BTTDVYVTDTUALJ-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at DOR (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 = 14.5 nM (pChEMBL 7.840000152587891)
Descriptors: MW 450.5, ALogP 3.64, HBA 4, HBD 2, PSA 64.01, QED 0.71
Compound (SMILES): COc1cc(O)c2c(=O)cc(-c3ccc(N4CCN(C)CC4)cc3)oc2c1N1CCNCC1
InChIKey: FXIMIJCGTDGDFQ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK4/CyclinD1 (unknown origin) by ADP-Glo assay
Measurement: IC50 = 311 nM (pChEMBL 6.510000228881836)
Descriptors: MW 450.54, ALogP 2.34, HBA 8, HBD 2, PSA 81.42, QED 0.63
Compound (SMILES): O=C1CC2Cc3ccsc3C2=NN1CCCCCN1CCN(Cc2cccc3c2ccn3S(=O)(=O)c2ccccc2)CC1
InChIKey: AVIFTUQCMKTSNJ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition and measured for 5 mins by Ellman's spectrophotometric method
Measurement: IC50 = 6890 nM (pChEMBL 5.159999847412109)
Descriptors: MW 615.83, ALogP 5.04, HBA 8, HBD 0, PSA 78.22, QED 0.23
Compound (SMILES): COc1ccc(S(=O)(=O)Nc2ccccc2C#Cc2ccc(C(=O)O)cc2)c2ncccc12
InChIKey: MENPFOQPGOROOE-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Inhibition of human MCT4 in human SNU-398 cells assessed as inhibition of 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 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 458.5, ALogP 4.14, HBA 5, HBD 2, PSA 105.59, QED 0.44
Compound (SMILES): COc1ccc(CO[C@H]2CCCN(Cc3ccc(C)cc3)C2)cc1F
InChIKey: BXHPZOSDEOGGRA-IBGZPJMESA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]SCH23390 from D1 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 343.44, ALogP 4.32, HBA 3, HBD 0, PSA 21.7, QED 0.78
Compound (SMILES): C=CC(=O)N1CC2(CC(n3nc(-c4ccc5[nH]ncc5c4)c(-c4c(Cl)c(C)cc5[nH]ncc45)c3C)C2)C1
InChIKey: APRMCKQFBKENDU-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Scintillation Proximity Assay (SPA): Assays were run using 384-well plates (781207/Greiner) in which one column was designated as the high signal (no inhibition) control, and contained DMSO with no test compound, and another column was designated as the low signal control (maximal inhibition), and contained no protein. Serial dilutions of compounds to be tested were added to the assay plate (resulting in duplicate 11-point dose response with semi-log compound dilutions from 50 μM to 0.5 nM or from 5 μM to 0.05 nM for the most potent compounds). A 1/20 isotopic dilution of labeled (Compound B) and non-labeled covalent (Compound A) probe was prepared and added to all wells on the plate. The reaction was started by addition of KRasG12C (M1-K169, biotinylated on the N-terminus) to the compounds and incubated for 2 hours with continuous agitation allowing for full modification of KRasG12C with probe or test compounds. Final concentrations in an assay volume of 40 μL were 10 nM KRasG12C, 25 nM radio-ligand and 475 nM unlabelled ligand. The assay buffer contained 20 mM Tris-HCl pH 7.5 (Invitrogen), 150 mM NaCl (Sigma Aldrich), 0.1 mM MgCl2 (Sigma Aldrich), and 0.01% Tween-20 (Sigma Aldrich). Following addition of 50 μL of a 400 μg/ml. suspension of streptavidin-coated YSi beads (Perkin Elmer), plates were incubated for a further 30 min with continuous agitation before reading the plates on a scintillation counter (Topcount NXT 384 (Packard).
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 512.02, ALogP 5.59, HBA 5, HBD 2, PSA 95.49, QED 0.31
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3cc(CC#N)c(=O)n(C4CCCC4)c3n2)CC1
InChIKey: IRIKLLIKMPLYCS-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK4/cyclin D1 (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 = 0.48 nM (pChEMBL 9.319999694824219)
Descriptors: MW 430.53, ALogP 1.81, HBA 8, HBD 1, PSA 120.98, QED 0.77
Compound (SMILES): CC(N)C(=O)NC1CSCc2cc3cc(c2)CSCC(C(=O)NC(C)C(N)=O)NC(=O)C(CCCNC(=N)N)NC(=O)C(C(C)C)NC(=O)C(CC(N)=O)NC(=O)C(CSC3)NC(=O)C(C)NC(=O)C(CCCCN)NC(=O)C(Cc2ccccc2)NC1=O
InChIKey: KECRAMBCZUQJGL-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition of human fXIa using Boc-FSR-AMC as substrate assessed as inhibition constant by fluorescence plate reader analysis
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 1298.63
Compound (SMILES): CC[C@@H]1CN2CCc3c([nH]c4cccc(O[C@@H]5O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]5O)c34)[C@@H]2C[C@@H]1/C(=C\OC)C(=O)OC
InChIKey: PRYHOGCYPICMAJ-IRERNMKVSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Agonist activity at mouse MOR expressed in CHO cell membranes assessed as stimulation of [35S]-GTPgammaS binding incubated for 60 mins by scintillation spectroscopy analysis
Measurement: EC50 = 5778 nM (pChEMBL 5.239999771118164)
Descriptors: MW 560.6, ALogP 1.09, HBA 10, HBD 5, PSA 171.01, QED 0.19
Compound (SMILES): Cc1ccc(/C(=N\O)N2CCN(c3ccc(S(N)(=O)=O)cc3)CC2)cc1
InChIKey: JCLAINPBCVYCMR-CZIZESTLSA-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 = 93.4 nM (pChEMBL 7.03000020980835)
Descriptors: MW 374.47, ALogP 1.6, HBA 5, HBD 2, PSA 99.23, QED 0.37
Compound (SMILES): [11CH3]n1cc(CCNCc2ccc(/C=C/C(=O)NO)cc2)c2ccccc21
InChIKey: AEDUBEGTPWKDCX-UQCBPKKGSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of HDAC4 (unknown origin)
Measurement: IC50 = 655 nM (pChEMBL 6.179999828338623)
Descriptors: MW 349.43, ALogP 3.03, HBA 4, HBD 3, PSA 66.29, QED 0.27
Compound (SMILES): CC1=CC(C)=[N+]2C1=C(c1ccc(OCCn3cc(CCOCCOc4cc(C(=O)O)nc5c(C)c6nc(C(=O)O)cc(O)c6cc45)nn3)cc1)c1nc(C)cn1[B-]2(F)F
InChIKey: VOUATRAEWHCYOH-UHFFFAOYSA-N
Target: G-protein coupled receptor 35 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC97
Assay: Binding affinity to Nluc-fused human GPR35 expressed in CHO-K1 cells using furimazine as substrate incubated for 30 mins in presence of zaprinast followed by substrate addition by BERT-based equilibrium binding assay
Measurement: Kd = 17.9 nM (pChEMBL 7.75)
Descriptors: MW 806.59
Compound (SMILES): CC(O)(CCCc1ccc(F)cc1)c1cc(C(=O)N2Cc3ccccc3C2)ccc1O
InChIKey: DSLAFZCEXGDWJA-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 419.5, ALogP 4.92, HBA 3, HBD 2, PSA 60.77, QED 0.6
Compound (SMILES): NS(=O)(=O)c1ccc(N2CCN(/C(=N/O)c3ccncc3)CC2)cc1
InChIKey: OKWAUYUTKHCUHK-KNTRCKAVSA-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 = 52.3 nM (pChEMBL 7.28000020980835)
Descriptors: MW 361.43, ALogP 0.69, HBA 6, HBD 2, PSA 112.12, QED 0.36
Compound (SMILES): CCOCc1cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc2n(C2CCCC2)c1=O
InChIKey: IEJYZRBPCUHCNN-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 > 1200 nM (pChEMBL 5.921000003814697)
Descriptors: MW 449.58, ALogP 2.28, HBA 8, HBD 1, PSA 106.42, QED 0.69
Compound (SMILES): Cc1ccc(CS(=O)(=O)NC(=O)C2(C)CCN(c3nc4c(cc3C#N)C(=O)OC4)CC2)cc1
InChIKey: UDMPNYKEHCRGIV-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated for 10 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 468.54, ALogP 2.18, HBA 8, HBD 1, PSA 129.46, QED 0.66
Compound (SMILES): Cc1cn(-c2cccc(F)c2)c2cc(F)c(C(=O)NS(C)(=O)=O)cc12
InChIKey: SDTKWQXAMOIFHH-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 = 31000 nM (pChEMBL 4.510000228881836)
Descriptors: MW 364.37, ALogP 2.91, HBA 4, HBD 1, PSA 68.17, QED 0.78
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)CN)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]3CSSC[C@H](NC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)O)CSSC[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC3=O)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)N2
InChIKey: JANHCNHLQNQZQS-WZMYVTDBSA-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 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 3346.91
Compound (SMILES): O=C(O)c1ccnc(C(=O)NS(=O)(=O)c2ccc(C(F)(F)F)cc2)c1
InChIKey: SMDDFDIPQUPVHJ-UHFFFAOYSA-N
Target: RNA demethylase ALKBH5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P6C2
Assay: Inhibition of ALKBH5 (66 to 292 residues) (unknown origin) extracted from Escherichia coli BL21 (DE3) cells using m6A ssDNA as substrate measured after 6 hrs by fluorescence polarization assay
Measurement: IC50 = 28940 nM (pChEMBL 4.539999961853027)
Descriptors: MW 374.3, ALogP 1.92, HBA 5, HBD 2, PSA 113.43, QED 0.85
Compound (SMILES): Cn1c(=O)n(C)c2ccc3ccc4ccc1c2c43
InChIKey: FMSQVMMNJBNNML-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) preincubated for 10 mins followed by ATP addition and measured after 60 mins by ADP-Glo assay
Measurement: IC50 = 11680 nM (pChEMBL 4.929999828338623)
Descriptors: MW 236.27, ALogP 2.62, HBA 3, HBD 0, PSA 26.93, QED 0.46
Compound (SMILES): Cc1[nH]c(C(=O)Nc2nc3c(N4CCOCC4)cc(C(=O)O)cc3s2)c(Cl)c1Cl
InChIKey: XMRMYIYEEWALOZ-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Pseudomonas aeruginosa
UniProt: Q9I7C2
Assay: Inhibition of Pseudomonas aeruginosa DNA gyrase supercoiling incubated for 30 mins in presence of ATP by ethidium bromide staining based analysis
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 455.32, ALogP 4.03, HBA 6, HBD 3, PSA 107.55, QED 0.55
Compound (SMILES): CN1CC2CCC(C1=O)N2c1ncc2[nH]nc(-c3cnn([C@H]4CC[C@H](O)CC4)c3)c2n1
InChIKey: GKEASMTXYHOIFG-NYKLAOPUSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: Phosphorylated (P): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including phosphorylated (P)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 422.49, ALogP 1.5, HBA 8, HBD 2, PSA 116.06, QED 0.66
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)Nc2n[nH]c3ccc(-c4cncc(NC[C@@H](O)c5ccccc5)c4)cc23)cc1
InChIKey: VSTRBHWJZOVRDC-HHHXNRCGSA-N
Target: Cyclin-dependent kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00526
Assay: Inhibition of CDK3 (unknown origin)
Measurement: IC50 = 1837 nM (pChEMBL 5.739999771118164)
Descriptors: MW 518.58, ALogP 5.15, HBA 6, HBD 5, PSA 132.03, QED 0.17