lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C)C(=O)CCc1nc(-c2ccccc2)c(-c2ccccc2)o1
InChIKey: JZMZNOFEMDPCKX-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 4immunitygroup A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P22736
Assay: Inverse agonist activity at human Nur77 (358 to 598 residues) transfected in HEK293T cells incubated for 16 hrs by firefly/renilla based Dual-Glo luciferase assay
Measurement: IC50 = 37000 nM (pChEMBL 4.429999828338623)
Descriptors: MW 320.39, ALogP 4.03, HBA 3, HBD 0, PSA 46.34, QED 0.71
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2ccnc3[nH]ccc23)nc2c1ccn2S(C)(=O)=O
InChIKey: IJEDYDGSAXSVPY-GFCCVEGCSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of human MER
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.48, ALogP 2.01, HBA 8, HBD 1, PSA 106, QED 0.55
Compound (SMILES): Cc1cc(C#N)cc(C)c1C(=O)N[C@@H](CNC(=O)Cn1c(=O)[nH]c2ncccc21)C(=O)O
InChIKey: ZBVHHUZMSQXUEW-AWEZNQCLSA-N
Target: Integrin alpha-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Inhibition of recombinant human Integrin alpha4beta1 using TMB as substrate incubated for 2 hrs in presence of VCAM-1 by ELISA
Measurement: IC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 436.43, ALogP 0.21, HBA 7, HBD 4, PSA 169.97, QED 0.41
Compound (SMILES): CCN(CCN)c1ccc(Nc2cc(NC3CC3)n3ncc(C#N)c3n2)cc1-n1cnnc1
InChIKey: VVIQQTQLDDARAW-UHFFFAOYSA-N
Target: Homeodomain-interacting protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NE63
Assay: Inhibition of human HIPK4 expressed in HEK293 cells incubated for 2 hrs by NanoBRET assay
Measurement: IC50 = 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 443.52, ALogP 2.28, HBA 11, HBD 3, PSA 138.01, QED 0.36
Compound (SMILES): O=C1NCCc2cccc(c2)Nc2ncc(Cl)c(n2)Nc2cc1[nH]n2
InChIKey: HWVVDXRDQZQPOL-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 26 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P289
Assay: Binding affinity to C-terminal full length human MST4 expressed in permeabilized HEK293T cells incubated for 2 hrs by NanoBRET assay
Measurement: EC50 = 10270 nM (pChEMBL 4.989999771118164)
Descriptors: MW 355.79, ALogP 2.63, HBA 6, HBD 4, PSA 107.62, QED 0.49
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](N)CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)[C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C)[C@@H](C)O
InChIKey: TUNMPZKBFKWZSA-MUTRJDDOSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32214
Assay: Displacement of 125I-Calcitonin from rat CTR expressed in Baby hamster kidney cell membrane incubated for 120 mins by SPA method
Measurement: IC50 = 17.11 nM (pChEMBL 7.769999980926514)
Descriptors: MW 3979.4
Compound (SMILES): COc1cc(C2NCCc3c2[nH]c2ccccc32)ccc1OCc1cc(C(F)(F)F)cc(C(F)(F)F)c1
InChIKey: MOOWKXDYPKYTBJ-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15303
Assay: Inhibition of wild type GST-tagged HER4 catalytic domain (unknown origin) expressed in insect cells using poly(Glu-Tyr) as substrate incubated for 6 mins by ELISA
Measurement: IC50 = 86500 nM (pChEMBL 4.059999942779541)
Descriptors: MW 520.47, ALogP 7.03, HBA 3, HBD 2, PSA 46.28, QED 0.28
Compound (SMILES): CC1(C)CC(=O)c2c(C(F)(F)F)nn(Cc3ccc(C(=O)NO)cc3)c2C1
InChIKey: AUEDMSVXWKXTGU-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of human recombinant HDAC4 using Boc-Lys(tri-fluoroacetyl)-AMC as substrate by fluorescence based analysis
Measurement: IC50 = 4990 nM (pChEMBL 5.300000190734863)
Descriptors: MW 381.35, ALogP 3.22, HBA 5, HBD 2, PSA 84.22, QED 0.63
Compound (SMILES): Cc1ccc([C@@H](NC(=O)[C@@H](F)c2ccc(Cl)cc2)[C@@H](C)C(=O)O)cc1OCC(C)(C)C#N
InChIKey: GXGNPULBKHMWLA-NQERJWCQSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes
Measurement: IC50 = 6200 nM (pChEMBL 5.210000038146973)
Descriptors: MW 460.93, ALogP 5.17, HBA 4, HBD 2, PSA 99.42, QED 0.54
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCC3(CC2)CC(N2CCC[C@H]2c2ccccc2C2CC2)C3)cc1Oc1cnc2[nH]ccc2c1
InChIKey: IVXFXSGHRVGVIZ-WBCKFURZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes by LC-MS/MS analysis
Measurement: IC50 = 7890 nM (pChEMBL 5.099999904632568)
Descriptors: MW 860.05, ALogP 8.68, HBA 11, HBD 3, PSA 172.03, QED 0.08
Compound (SMILES): CC[C@@]1(C(=O)O)C[C@H]1[C@H](N)C(=O)O.Cl
InChIKey: BGPCGYBGJFZOPY-CGOLMLKISA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31423
Assay: Agonist activity at rat mGluR4 receptor expressed in HEK293 cells by IP-1 HTRF assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 187.19, ALogP -0.1, HBA 3, HBD 3, PSA 100.62, QED 0.57
Compound (SMILES): CN(C)c1cccc2c(S(=O)(=O)NCCOCCOC(=O)NC34CC5CC(CC(NCC(=O)N6Cc7cc(F)c(F)cc7C6)(C5)C3)C4)cccc12
InChIKey: CUQPRCWWJPLANH-UHFFFAOYSA-N
Target: Prolyl endopeptidase (SINGLE PROTEIN), Homo sapiens
UniProt: P48147
Assay: Inhibition of recombinant human PREP
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 725.86, ALogP 4.43, HBA 8, HBD 3, PSA 129.31, QED 0.22
Compound (SMILES): N[C@H]1CCN(c2ccnc3ccc(-c4ccc(C(F)(F)F)nc4)nc23)C1
InChIKey: KPHPXSWPALMBKV-LBPRGKRZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 359.36, ALogP 3.25, HBA 5, HBD 1, PSA 67.93, QED 0.76
Compound (SMILES): CC(=O)N[C@H]1Cc2ccc(cc2)OC/C=C\CNC(=O)CC[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)c2nc3ccccc3s2)NC(=O)[C@H](CC(C)C)NC1=O
InChIKey: LNIRCTXHOVOSQG-CJMRSYTISA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of recombinant thrombin (unknown origin) using D-Phe-Pip-Arg-pNA as chromogenic substrate preincubated for 30 mins followed by substrate addition by absorbance based analysis
Measurement: IC50 = 1240 nM (pChEMBL 5.909999847412109)
Descriptors: MW 789.96, ALogP 1.84, HBA 10, HBD 8, PSA 246.59, QED 0.05
Compound (SMILES): CN(C(=O)CCc1ccoc1)[C@@H]1CC[C@@]2(O)[C@H]3Cc4cccc5c4[C@@]2(CCN3CC2CC2)[C@H]1O5.Cl
InChIKey: WBIGRZFMPUSILZ-CYZBAFPSSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cells increase in [35S]GTPgammaS binding measured after 1.5 hrs by scintillation counter analysis
Measurement: EC50 = 5783 nM (pChEMBL 5.239999771118164)
Descriptors: MW 462.59, ALogP 3.3, HBA 5, HBD 1, PSA 66.15, QED 0.71
Compound (SMILES): CN(C)C(=O)CCc1nc(-c2ccccc2)c(-c2ccccc2Cl)o1
InChIKey: ONNLRDYEHSIWHB-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 4immunitygroup A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P22736
Assay: Inverse agonist activity at human Nur77 (358 to 598 residues) transfected in HEK293T cells incubated for 16 hrs by firefly/renilla based Dual-Glo luciferase assay
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 354.84, ALogP 4.68, HBA 3, HBD 0, PSA 46.34, QED 0.67
Compound (SMILES): CN1CCN(C(=O)c2cc(Br)cc([N+](=O)[O-])c2N[C@@H]2CCCC[C@@H]2NC(=O)c2cc(=O)[nH]c3c(F)cccc23)CC1
InChIKey: FZNWILPXXNKETO-YADHBBJMSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human Cathepsin K using Z-Phe-Arg-AMC as substrate incubated for 10 mins by FRET-enzymatic assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 629.49, ALogP 3.88, HBA 7, HBD 3, PSA 140.68, QED 0.28
Compound (SMILES): CN(C(=O)/C=C/c1ccco1)[C@H]1CC[C@@]2(O)[C@H]3Cc4cccc5c4[C@@]2(CCN3CC2CC2)[C@H]1O5.Cl
InChIKey: OYYVXZDQIZNZGA-HNPKZZEHSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cells increase in [35S]GTPgammaS binding measured after 1.5 hrs by scintillation counter analysis
Measurement: EC50 = 439.7 nM (pChEMBL 6.360000133514404)
Descriptors: MW 460.57, ALogP 3.38, HBA 5, HBD 1, PSA 66.15, QED 0.69
Compound (SMILES): Cl.O=C(/C=C/c1ccco1)N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5
InChIKey: WLFWKBMOMGVGSW-FLPAALAHSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Partial agonist activity at human DOR expressed in CHO cells increase in [35S]GTPgammaS binding measured after 1.5 hrs by scintillation counter analysis
Measurement: EC50 = 13.07 nM (pChEMBL 7.880000114440918)
Descriptors: MW 462.55, ALogP 2.75, HBA 6, HBD 3, PSA 95.17, QED 0.59
Compound (SMILES): CCOC(=O)c1cc2ccc(OCC(=O)NCCc3ccc(S(N)(=O)=O)cc3)cc2oc1=O
InChIKey: VXFTZRKWJZUQLA-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of human recombinant CA7 assessed as inhibition constant incubated for 45 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 474.49, ALogP 1.35, HBA 8, HBD 2, PSA 155, QED 0.35
Compound (SMILES): NS(=O)(=O)c1c(CC2CCNCC2)ccc(-c2ccc(C3CCNCC3)cc2)c1-c1nn[nH]n1
InChIKey: LHOHTNKBXFSQBC-UHFFFAOYSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of Cav1.2 channel (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 481.63, ALogP 2.19, HBA 7, HBD 4, PSA 138.68, QED 0.42
Compound (SMILES): O=C(CCCCC1SCC2NC(=O)NC21)NCCOCCOC(=O)NC12CC3CC(CC(NCC(=O)N4Cc5cc(F)c(F)cc5C4)(C3)C1)C2
InChIKey: SCBVFHDXILJJQY-UHFFFAOYSA-N
Target: Prolyl endopeptidase (SINGLE PROTEIN), Homo sapiens
UniProt: P48147
Assay: Inhibition of recombinant human PREP
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 718.87, ALogP 3.07, HBA 8, HBD 5, PSA 150.13, QED 0.14
Compound (SMILES): Cc1c(Cl)c2c(Cl)c(C)c1-c1c(-c3ccc(F)cc3)sc3ncnc(c13)O[C@@H](C(=O)O)Cc1cc(ccc1OCc1ccnc(-c3ccc(OC[C@@H]4COCCO4)cc3)n1)OC[C@@H](CN1CCN(C)CC1)O2
InChIKey: BOMNURVTAHAEBQ-JOVQOBAQSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Exemplary MCL-1 Inhibitors Bind MCL-1: The ability of the exemplary MCL-1 inhibitors of Examples 1 through 151 to bind MCL-1 was demonstrated using the Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) Assay. Tb-anti-GST antibody was purchased from Invitrogen (Catalog No. PV4216). The ability of exemplary MCL-1 inhibitors Example 1 to Example 3 to compete with probe F-Bak for binding MCL-1 was demonstrated using a Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) binding assay.MethodFor the assay, an acoustic dispenser was used to prepare dilution series from 10 mM test compounds in 100% DMSO and directly transfer 160 nL into low volume 384-well assay plates. 8 μL of a protein/probe/antibody mix was then added to each well resulting in final concentrations listed below: Test compound: 11 three-fold dilutions beginning at 25 μMProtein: GST-MCL-1  1 nM Antibody Tb-anti-GST  1 nM Probe: F-Bak 100 nMThe samples were then mixed on a shaker for 1 minute and incubated for an additional 2 hours at room temperature. For each assay plate, a probe/antibody and protein/antibody/probe mixture were included as a negative and a positive control, respectively. Fluorescence was measured on the Envision (Perkin Elmer) using a 340/35 nm excitation filter and 520/525 (F-Bak) and 495/510 nm (Tb-labeled anti-his antibody) emission filters. Dissociation constants (Ki) were determined using Wang's equation (Wang, 1995, FEBS Lett. 360:111-114). The TR-FRET assay can be performed in the presence of varying concentrations of human serum (HS) or fetal bovine serum (FBS).
Measurement: Ki = 0.036 nM (pChEMBL 10.4399995803833)
Descriptors: MW 1037.99
Compound (SMILES): NS(=O)(=O)c1c(C(F)(F)F)ccc(-c2ccc(C3CCN(CC4CNC4)CC3)cc2)c1-c1nn[nH]n1
InChIKey: OASRXZZSPMUCKN-UHFFFAOYSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of Cav1.2 channel (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 521.57, ALogP 2.6, HBA 7, HBD 3, PSA 129.89, QED 0.45
Compound (SMILES): CCCNNC(=O)c1ccc(Nc2nccc(N(C)c3ccc4c(C)n(C)nc4c3)n2)cc1
InChIKey: QTIHZRQNFPNCHT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P35916
Assay: Inhibition of VEGFR3 (unknown origin)
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 444.54, ALogP 3.83, HBA 8, HBD 3, PSA 100, QED 0.28
Compound (SMILES): Cn1c(=O)c2c(nc(NCCc3c[nH]c4ccccc34)n2Cc2ccc(Cl)cc2)n(C)c1=O
InChIKey: FHFDQEPXKZVEOI-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human CB2 receptor expressed in CHO cells assessed as inhibition constant by radioligand competition binding assay
Measurement: Ki = 481 nM (pChEMBL 6.320000171661377)
Descriptors: MW 462.94, ALogP 3.27, HBA 7, HBD 2, PSA 89.64, QED 0.41
Compound (SMILES): CC(=O)N[C@H]1CCCCn2cc(nn2)C[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)c2nc3ccccc3s2)NC(=O)[C@H](CC(C)C)NC1=O
InChIKey: NNOFPIZGQIFDSZ-OJJQZRKESA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of recombinant thrombin (unknown origin) using D-Phe-Pip-Arg-pNA as chromogenic substrate preincubated for 30 mins followed by substrate addition by absorbance based analysis
Measurement: IC50 = 9540 nM (pChEMBL 5.019999980926514)
Descriptors: MW 695.85, ALogP 0.77, HBA 11, HBD 7, PSA 238.97, QED 0.06
Compound (SMILES): C=CC(=O)Nc1cccc(CN2C(=O)N(c3cc(OC)cc(OC)c3)Cc3cnc(Nc4c(C)cccc4NC(=O)C=C)nc32)c1
InChIKey: CMOLZUKSMQFAMH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 C552A mutant using preincubated for 30 mins followed by ATP plus poly (4:1 glu, tyr) addition and measured after 30 mins by ADP-Glo reagent based plate reader analysis
Measurement: IC50 = 1596 nM (pChEMBL 5.800000190734863)
Descriptors: MW 619.68, ALogP 5.94, HBA 8, HBD 3, PSA 138.02, QED 0.18
Compound (SMILES): CC(C)N1CCN(c2ccc(C(=O)n3nc(-c4ccccn4)nc3N)c3ccccc23)CC1
InChIKey: FVIOGCSRFRGENP-UHFFFAOYSA-N
Target: Plasminogen (SINGLE PROTEIN), Homo sapiens
UniProt: P00747
Assay: Inhibition of plasmin (unknown origin) using PyroGlu-Phe-Lys-pNA.HCl as chromogenic substrate incubated for 20 mins followed by substrate addition by spectrophotometric analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 441.54, ALogP 3.29, HBA 8, HBD 1, PSA 93.17, QED 0.52
Compound (SMILES): CN(C)CCNC=C1C(=O)CC(c2c(Cl)c(Cl)cc3[nH]ccc23)CC1=O
InChIKey: PZZMLUYOSFDDHG-RAXLEYEMSA-N
Target: Microtubule-associated protein 1 light chain 3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H492
Assay: Inhibition of LC3A (unknown origin) by Alphascreen assay
Measurement: IC50 = 32.8 nM (pChEMBL 7.480000019073486)
Descriptors: MW 394.3, ALogP 3.53, HBA 4, HBD 2, PSA 65.2, QED 0.46
Compound (SMILES): COc1cc(F)c(O[C@H]2CC[C@@](C)(C(=O)O)CC2)cc1C(=O)N[C@H]1[C@@H]2CC[C@@H](C2)[C@H]1C(=O)NCC1(C)CCC1
InChIKey: LYUYYIGCZIZIGF-LHEALVPGSA-N
Target: Translocator protein (SINGLE PROTEIN), Homo sapiens
UniProt: P30536
Assay: Inhibition of human TSPO
Measurement: IC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 544.66, ALogP 4.7, HBA 5, HBD 3, PSA 113.96, QED 0.42
Compound (SMILES): CC(C)c1ccccc1[C@@H]1CCCN1C1CC2(CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NC[C@@H]5COCCO5)c([N+](=O)[O-])c4)c(Oc4cnc5[nH]ccc5c4)c3)CC2)C1
InChIKey: SEOFRNNPVLILNV-OCUJDILZSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 864.04, ALogP 7.92, HBA 12, HBD 3, PSA 181.26, QED 0.08
Compound (SMILES): O=C(Cn1cc(CN2CCN(c3ccnc4cc(Cl)ccc34)CC2)nn1)Nc1cccc([N+](=O)[O-])c1
InChIKey: XNWXHOVKTNUGEB-UHFFFAOYSA-N
Target: Falcipain-3 (SINGLE PROTEIN), Plasmodium falciparum 3D7
UniProt: Q8IIL0
Assay: Inhibition of N-terminal 6His-tagged recombinant Plasmodium falciparum FP3 expressed in Escherichia coli M15 using Z-Phe-Arg-AMC as substrate measured after 30 mins by microplate reader analysis
Measurement: IC50 = 31800 nM (pChEMBL 4.5)
Descriptors: MW 506.95, ALogP 3.35, HBA 9, HBD 1, PSA 122.32, QED 0.3
Compound (SMILES): O=C(Cn1c(=O)[nH]c2ncccc21)NC[C@H](NC(=O)c1c(Cl)cccc1Cl)C(=O)O
InChIKey: PQWRZQIWMNBRRU-NSHDSACASA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Inhibition of recombinant human Integrin alpha5beta1 using TMB as substrate incubated for 2 hrs in presence of fibronectin by ELISA
Measurement: IC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 452.25, ALogP 1.03, HBA 6, HBD 4, PSA 146.18, QED 0.42
Compound (SMILES): COc1ccc(NC(=O)OC[C@H]2COc3c(cc(Cl)c4nc(-c5cc(C)cc6nc(OC)cnc56)sc34)O2)cn1
InChIKey: GZRBIJYGDCLWCQ-OAHLLOKOSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes
Measurement: IC50 > 6000 nM (pChEMBL 5.2220001220703125)
Descriptors: MW 580.02, ALogP 5.67, HBA 11, HBD 1, PSA 126.81, QED 0.27
Compound (SMILES): CN(C)C(=O)CCc1nc(-c2ccccc2)c(-c2ccccc2)o1
InChIKey: JZMZNOFEMDPCKX-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 4 group A member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92570
Assay: Inverse agonist activity at human NOR-1 (393 to 626 residues) transfected in HEK293T cells incubated for 16 hrs by firefly/renilla based Dual-Glo luciferase assay
Measurement: IC50 = 39000 nM (pChEMBL 4.409999847412109)
Descriptors: MW 320.39, ALogP 4.03, HBA 3, HBD 0, PSA 46.34, QED 0.71
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2ccnc3[nH]ccc23)nc2c1ccn2S(C)(=O)=O
InChIKey: IJEDYDGSAXSVPY-GFCCVEGCSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of human ABL
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.48, ALogP 2.01, HBA 8, HBD 1, PSA 106, QED 0.55
Compound (SMILES): Cc1cc(C#N)cc(C)c1C(=O)N[C@@H](CNC(=O)Cn1c(=O)[nH]c2ncccc21)C(=O)O
InChIKey: ZBVHHUZMSQXUEW-AWEZNQCLSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Inhibition of recombinant human Integrin alpha5beta1 using TMB as substrate incubated for 2 hrs in presence of fibronectin by ELISA
Measurement: IC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 436.43, ALogP 0.21, HBA 7, HBD 4, PSA 169.97, QED 0.41
Compound (SMILES): CCN(CCN)c1ccc(Nc2cc(NC3CC3)n3ncc(C#N)c3n2)cc1-n1cnnc1
InChIKey: VVIQQTQLDDARAW-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of human CLK4 expressed in HEK293 cells incubated for 2 hrs by NanoBRET assay
Measurement: IC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 443.52, ALogP 2.28, HBA 11, HBD 3, PSA 138.01, QED 0.36
Compound (SMILES): CC1(C)CC(=O)c2c(C(F)(F)F)nn(Cc3ccc(C(=O)NO)cc3)c2C1
InChIKey: AUEDMSVXWKXTGU-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of human recombinant HDAC5 using Boc-Lys(tri-fluoroacetyl)-AMC as substrate by fluorescence based analysis
Measurement: IC50 = 15900 nM (pChEMBL 4.800000190734863)
Descriptors: MW 381.35, ALogP 3.22, HBA 5, HBD 2, PSA 84.22, QED 0.63
Compound (SMILES): Cc1ccc([C@@H](NC(=O)[C@@H](F)c2ccc(Cl)cc2)[C@@H](C)C(=O)O)cc1OCC(C)(C)C#N
InChIKey: GXGNPULBKHMWLA-NQERJWCQSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 460.93, ALogP 5.17, HBA 4, HBD 2, PSA 99.42, QED 0.54
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCC3(CC2)CC(N2CCC[C@H]2c2ccccc2C2CC2)C3)cc1Oc1cnc2[nH]ccc2c1
InChIKey: IVXFXSGHRVGVIZ-WBCKFURZSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Bcl-2/Bcl-X TR-FRET Assay: Compounds disclosed herein were tested for blocking of Bcl-2/Bcl-X protein with its ligand in an assay based on Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) methodology. Recombinant human 0.05 nM Bcl-2/0.03 nM Bcl-X protein was pre-incubated with a serial dilution of compounds disclosed herein (maximum concentration is 0.1 μM for Bcl-2 assay, and 10 μM for Bcl-xl assay, 3-fold serially diluted, 10 points; or maximum concentration is 0.02 μM for Bcl-2 assay, and 2 μM for Bcl-xl assay, 3-fold serially diluted, 10 points) at room temperature for 0.5 hour in an assay buffer containing 20 mM potassium phosphate buffer, pH 7.5, 50 mM NaCl, 1 mM EDTA, 0.05% Tween-20, 0.01% BSA. Then the FITC labeled Bak peptide Ac-GQVGRQLAIIGDK(FITC)INR-amide (0.5 nM for Bcl-2, 0.3 nM for Bcl-xl) and MAb Anti 6His Tb cryptate Gold were added to plate and further incubated at room temperature for 1 hour. The TR-FRET signals (337 nm-520 nm-490 nm) were read on BMG PHERAstar FSX instrument. The inhibition percentage of Bcl-2/Bcl-X interaction with its ligand in presence of increasing concentrations of compounds was calculated based on the TR-FRET signals. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Graphpad Prism software. To improve the assay sensitivity and test more potent compounds in the present application, the bcl-2 concentration was reduced in method B.
Measurement: IC50 = 0.039 nM (pChEMBL 10.40999984741211)
Descriptors: MW 860.05, ALogP 8.68, HBA 11, HBD 3, PSA 172.03, QED 0.08
Compound (SMILES): CC[C@@]1(C(=O)O)C[C@H]1[C@H](N)C(=O)O.Cl
InChIKey: BGPCGYBGJFZOPY-CGOLMLKISA-N
Target: Metabotropic glutamate receptor 6 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35349
Assay: Agonist activity at rat mGluR6 receptor expressed in HEK293 cells by IP-1 HTRF assay
Measurement: EC50 = 26300 nM (pChEMBL 4.579999923706055)
Descriptors: MW 187.19, ALogP -0.1, HBA 3, HBD 3, PSA 100.62, QED 0.57
Compound (SMILES): N[C@H]1CCN(c2ccnc3ccc(-c4ccc(C(F)(F)F)nc4)nc23)C1
InChIKey: KPHPXSWPALMBKV-LBPRGKRZSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 359.36, ALogP 3.25, HBA 5, HBD 1, PSA 67.93, QED 0.76
Compound (SMILES): CN(C)C(=O)CCc1nc(-c2ccccc2)c(-c2ccccc2Cl)o1
InChIKey: ONNLRDYEHSIWHB-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 4 group A member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92570
Assay: Inverse agonist activity at human NOR-1 (393 to 626 residues) transfected in HEK293T cells incubated for 16 hrs by firefly/renilla based Dual-Glo luciferase assay
Measurement: IC50 = 29000 nM (pChEMBL 4.539999961853027)
Descriptors: MW 354.84, ALogP 4.68, HBA 3, HBD 0, PSA 46.34, QED 0.67
Compound (SMILES): CN1CCN(C(=O)c2cc(Br)cc([N+](=O)[O-])c2N[C@@H]2CCCC[C@@H]2NC(=O)c2cc(=O)[nH]c3c(F)cccc23)CC1
InChIKey: FZNWILPXXNKETO-YADHBBJMSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of human Cathepsin L using Z-Phe-Arg-AMC as substrate incubated for 10 mins by FRET-enzymatic assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 629.49, ALogP 3.88, HBA 7, HBD 3, PSA 140.68, QED 0.28
Compound (SMILES): CCOC(=O)c1cc2ccc(OCC(=O)NCCc3ccc(S(N)(=O)=O)cc3)cc2oc1=O
InChIKey: VXFTZRKWJZUQLA-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human recombinant CA12 assessed as inhibition constant incubated for 45 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 49.4 nM (pChEMBL 7.309999942779541)
Descriptors: MW 474.49, ALogP 1.35, HBA 8, HBD 2, PSA 155, QED 0.35
Compound (SMILES): NS(=O)(=O)c1c(CC2CCNCC2)ccc(-c2ccc(C3CCNCC3)cc2)c1-c1nn[nH]n1
InChIKey: LHOHTNKBXFSQBC-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 481.63, ALogP 2.19, HBA 7, HBD 4, PSA 138.68, QED 0.42
Compound (SMILES): Cc1c(Cl)c2c(Cl)c(C)c1-c1c(-c3ccc(F)cc3)sc3ncnc(c13)O[C@@H](C(=O)O)Cc1cc(ccc1OCc1ccnc(-c3ccc(OC[C@@H]4COCCO4)cc3)n1)OC[C@@H](CN1CCN(C)CC1)O2
InChIKey: BOMNURVTAHAEBQ-JOVQOBAQSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Exemplary MCL-1 Inhibitors Bind MCL-1 in the presence of 10% HS: The ability of the exemplary MCL-1 inhibitors of Examples 1 through 151 to bind MCL-1 was demonstrated using the Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) Assay. Tb-anti-GST antibody was purchased from Invitrogen (Catalog No. PV4216). The ability of exemplary MCL-1 inhibitors Example 1 to Example 3 to compete with probe F-Bak for binding MCL-1 was demonstrated using a Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) binding assay.MethodFor the assay, an acoustic dispenser was used to prepare dilution series from 10 mM test compounds in 100% DMSO and directly transfer 160 nL into low volume 384-well assay plates. 8 μL of a protein/probe/antibody mix was then added to each well resulting in final concentrations listed below: Test compound: 11 three-fold dilutions beginning at 25 μMProtein: GST-MCL-1  1 nM Antibody Tb-anti-GST  1 nM Probe: F-Bak 100 nMThe samples were then mixed on a shaker for 1 minute and incubated for an additional 2 hours at room temperature. For each assay plate, a probe/antibody and protein/antibody/probe mixture were included as a negative and a positive control, respectively. Fluorescence was measured on the Envision (Perkin Elmer) using a 340/35 nm excitation filter and 520/525 (F-Bak) and 495/510 nm (Tb-labeled anti-his antibody) emission filters. Dissociation constants (Ki) were determined using Wang's equation (Wang, 1995, FEBS Lett. 360:111-114). The TR-FRET assay can be performed in the presence of varying concentrations of human serum (HS) or fetal bovine serum (FBS). Compounds were tested in the presence of 10% HS.
Measurement: Ki = 0.92 nM (pChEMBL 9.039999961853027)
Descriptors: MW 1037.99
Compound (SMILES): NS(=O)(=O)c1c(C(F)(F)F)ccc(-c2ccc(C3CCN(CC4CNC4)CC3)cc2)c1-c1nn[nH]n1
InChIKey: OASRXZZSPMUCKN-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 521.57, ALogP 2.6, HBA 7, HBD 3, PSA 129.89, QED 0.45
Compound (SMILES): Cn1c(=O)c2c(nc(NCCc3c[nH]c4ccccc34)n2Cc2ccc(Cl)cc2)n(C)c1=O
InChIKey: FHFDQEPXKZVEOI-UHFFFAOYSA-N
Target: N-arachidonyl glycine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q14330
Assay: Agonist activity at human GPR18-eYFP and Renilla luc expressed in CHO cells assessed as beta-arrestin2 recruitment by BRET/beta-arrestin2 enzyme complementation assay
Measurement: EC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 462.94, ALogP 3.27, HBA 7, HBD 2, PSA 89.64, QED 0.41
Compound (SMILES): CC(C)N1CCN(c2ccc(C(=O)n3nc(-c4ccccn4)nc3N)c3ccccc23)CC1
InChIKey: FVIOGCSRFRGENP-UHFFFAOYSA-N
Target: Tissue-type plasminogen activator (SINGLE PROTEIN), Homo sapiens
UniProt: P00750
Assay: Inhibition of tPA (unknown origin) using H-D-lle-Pro-Arg-pNA-2HCl as chromogenic substrate incubated for 20 mins followed by substrate addition by spectrophotometric analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 441.54, ALogP 3.29, HBA 8, HBD 1, PSA 93.17, QED 0.52
Compound (SMILES): CN(C)CCNC=C1C(=O)CC(c2c(Cl)c(Cl)cc3[nH]ccc23)CC1=O
InChIKey: PZZMLUYOSFDDHG-RAXLEYEMSA-N
Target: Microtubule-associated protein 1 light chain 3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZQ8
Assay: Inhibition of LC3B (unknown origin) by Alphascreen assay
Measurement: IC50 = 17.4 nM (pChEMBL 7.760000228881836)
Descriptors: MW 394.3, ALogP 3.53, HBA 4, HBD 2, PSA 65.2, QED 0.46
Compound (SMILES): COc1cc(F)c(O[C@H]2CC[C@@](C)(C(=O)O)CC2)cc1C(=O)N[C@H]1[C@@H]2CC[C@@H](C2)[C@H]1C(=O)NCC1(C)CCC1
InChIKey: LYUYYIGCZIZIGF-LHEALVPGSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Inhibition of human DRD3
Measurement: IC50 = 63095.73 nM (pChEMBL 4.199999809265137)
Descriptors: MW 544.66, ALogP 4.7, HBA 5, HBD 3, PSA 113.96, QED 0.42
Compound (SMILES): CC(C)c1ccccc1[C@@H]1CCCN1C1CC2(CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NC[C@@H]5COCCO5)c([N+](=O)[O-])c4)c(Oc4cnc5[nH]ccc5c4)c3)CC2)C1
InChIKey: SEOFRNNPVLILNV-OCUJDILZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 864.04, ALogP 7.92, HBA 12, HBD 3, PSA 181.26, QED 0.08
Compound (SMILES): O=C(Cn1cc(CN2CCN(c3ccnc4cc(Cl)ccc34)CC2)nn1)Nc1cccc([N+](=O)[O-])c1
InChIKey: XNWXHOVKTNUGEB-UHFFFAOYSA-N
Target: Falcipain 2 (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q9N6S8
Assay: Competitive inhibition of N-terminal 6His-tagged recombinant Plasmodium falciparum FP2 expressed in Escherichia coli M15 assessed as inhibition constant using Z-Phe-Arg-AMC as substrate measured after 30 mins by microplate reader analysis
Measurement: Ki = 527 nM (pChEMBL 6.28000020980835)
Descriptors: MW 506.95, ALogP 3.35, HBA 9, HBD 1, PSA 122.32, QED 0.3
Compound (SMILES): COc1ccc(NC(=O)OC[C@H]2COc3c(cc(Cl)c4nc(-c5cc(C)cc6nc(OC)cnc56)sc34)O2)cn1
InChIKey: GZRBIJYGDCLWCQ-OAHLLOKOSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes
Measurement: IC50 > 6000 nM (pChEMBL 5.2220001220703125)
Descriptors: MW 580.02, ALogP 5.67, HBA 11, HBD 1, PSA 126.81, QED 0.27
Compound (SMILES): CN(C)C(=O)CCc1nc(-c2ccccc2)c(-c2ccccc2)o1
InChIKey: JZMZNOFEMDPCKX-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 4 group A member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P43354
Assay: Inverse agonist activity at Gal4-fused wild type human Nurr1 transfected in HEK293T cells incubated for 16 hrs by firefly/renilla based Dual-Glo luciferase assay
Measurement: IC50 = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 320.39, ALogP 4.03, HBA 3, HBD 0, PSA 46.34, QED 0.71
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2ccnc3[nH]ccc23)nc2c1ccn2S(C)(=O)=O
InChIKey: IJEDYDGSAXSVPY-GFCCVEGCSA-N
Target: Serine/threonine-protein kinase BRSK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IWQ3
Assay: Inhibition of human BRSK2
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.48, ALogP 2.01, HBA 8, HBD 1, PSA 106, QED 0.55
Compound (SMILES): CCN(CCN)c1ccc(Nc2cc(NC3CC3)n3ncc(C#N)c3n2)cc1-n1cnnc1
InChIKey: VVIQQTQLDDARAW-UHFFFAOYSA-N
Target: Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform (SINGLE PROTEIN), Homo sapiens
UniProt: Q16816
Assay: Inhibition of human PHKG1 expressed in HEK293 cells incubated for 2 hrs by NanoBRET assay
Measurement: IC50 = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 443.52, ALogP 2.28, HBA 11, HBD 3, PSA 138.01, QED 0.36
Compound (SMILES): CC1(C)CC(=O)c2c(C(F)(F)F)nn(Cc3ccc(C(=O)NO)cc3)c2C1
InChIKey: AUEDMSVXWKXTGU-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human recombinant HDAC6 using fluorescent peptide p53 (379 to 382 residues) RHKK(Ac) as substrate by fluorescence based analysis
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 381.35, ALogP 3.22, HBA 5, HBD 2, PSA 84.22, QED 0.63
Compound (SMILES): Cc1ccc([C@@H](NC(=O)[C@@H](F)c2ccc(Cl)cc2)[C@@H](C)C(=O)O)cc1OCC(C)(C)C#N
InChIKey: GXGNPULBKHMWLA-NQERJWCQSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 460.93, ALogP 5.17, HBA 4, HBD 2, PSA 99.42, QED 0.54
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCC3(CC2)CC(N2CCC[C@H]2c2ccccc2C2CC2)C3)cc1Oc1cnc2[nH]ccc2c1
InChIKey: IVXFXSGHRVGVIZ-WBCKFURZSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Bcl-2/Bcl-X TR-FRET Assay: Compounds disclosed herein were tested for blocking of Bcl-2/Bcl-X protein with its ligand in an assay based on Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) methodology. Recombinant human 0.05 nM Bcl-2/0.03 nM Bcl-X protein was pre-incubated with a serial dilution of compounds disclosed herein (maximum concentration is 0.1 μM for Bcl-2 assay, and 10 μM for Bcl-xl assay, 3-fold serially diluted, 10 points; or maximum concentration is 0.02 μM for Bcl-2 assay, and 2 μM for Bcl-xl assay, 3-fold serially diluted, 10 points) at room temperature for 0.5 hour in an assay buffer containing 20 mM potassium phosphate buffer, pH 7.5, 50 mM NaCl, 1 mM EDTA, 0.05% Tween-20, 0.01% BSA. Then the FITC labeled Bak peptide Ac-GQVGRQLAIIGDK(FITC)INR-amide (0.5 nM for Bcl-2, 0.3 nM for Bcl-xl) and MAb Anti 6His Tb cryptate Gold were added to plate and further incubated at room temperature for 1 hour. The TR-FRET signals (337 nm-520 nm-490 nm) were read on BMG PHERAstar FSX instrument. The inhibition percentage of Bcl-2/Bcl-X interaction with its ligand in presence of increasing concentrations of compounds was calculated based on the TR-FRET signals. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Graphpad Prism software. To improve the assay sensitivity and test more potent compounds in the present application, the bcl-2 concentration was reduced in method B.
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 860.05, ALogP 8.68, HBA 11, HBD 3, PSA 172.03, QED 0.08
Compound (SMILES): CC[C@@]1(C(=O)O)C[C@H]1[C@H](N)C(=O)O.Cl
InChIKey: BGPCGYBGJFZOPY-CGOLMLKISA-N
Target: Metabotropic glutamate receptor 6 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35349
Assay: Agonist activity at rat mGluR6 receptor expressed in HEK293 cells by IP-1 HTRF assay
Measurement: EC50 = 26302.68 nM (pChEMBL 4.579999923706055)
Descriptors: MW 187.19, ALogP -0.1, HBA 3, HBD 3, PSA 100.62, QED 0.57
Compound (SMILES): N[C@H]1CCN(c2ccnc3ccc(-c4ccc(C(F)(F)F)nc4)nc23)C1
InChIKey: KPHPXSWPALMBKV-LBPRGKRZSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 359.36, ALogP 3.25, HBA 5, HBD 1, PSA 67.93, QED 0.76
Compound (SMILES): CN1CCN(C(=O)c2cc(Br)cc([N+](=O)[O-])c2N[C@@H]2CCCC[C@@H]2NC(=O)c2cc(=O)[nH]c3c(F)cccc23)CC1
InChIKey: FZNWILPXXNKETO-YADHBBJMSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using benzoyl-FVR-AMC as substrate incubated for 10 mins by FRET-enzymatic assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 629.49, ALogP 3.88, HBA 7, HBD 3, PSA 140.68, QED 0.28
Compound (SMILES): NS(=O)(=O)c1c(CC2CCNCC2)ccc(-c2ccc(C3CCNCC3)cc2)c1-c1nn[nH]n1
InChIKey: LHOHTNKBXFSQBC-UHFFFAOYSA-N
Target: Voltage-gated potassium channel, IKs; KCNQ1(Kv7.1)/KCNE1(MinK) (PROTEIN COMPLEX), Homo sapiens
UniProt: P15382
Assay: Inhibition of KCNQ1/KCNE1 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 481.63, ALogP 2.19, HBA 7, HBD 4, PSA 138.68, QED 0.42
Compound (SMILES): NS(=O)(=O)c1c(C(F)(F)F)ccc(-c2ccc(C3CCN(CC4CNC4)CC3)cc2)c1-c1nn[nH]n1
InChIKey: OASRXZZSPMUCKN-UHFFFAOYSA-N
Target: Voltage-gated potassium channel, IKs; KCNQ1(Kv7.1)/KCNE1(MinK) (PROTEIN COMPLEX), Homo sapiens
UniProt: P15382
Assay: Inhibition of KCNQ1/KCNE1 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 521.57, ALogP 2.6, HBA 7, HBD 3, PSA 129.89, QED 0.45
Compound (SMILES): CN(C)CCNC=C1C(=O)CC(c2c(Cl)c(Cl)cc3[nH]ccc23)CC1=O
InChIKey: PZZMLUYOSFDDHG-RAXLEYEMSA-N
Target: Microtubule-associated protein 1 light chain 3 gamma (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXW4
Assay: Inhibition of LC3C (unknown origin) by Alphascreen assay
Measurement: IC50 = 4520 nM (pChEMBL 5.340000152587891)
Descriptors: MW 394.3, ALogP 3.53, HBA 4, HBD 2, PSA 65.2, QED 0.46
Compound (SMILES): CC(C)c1ccccc1[C@@H]1CCCN1C1CC2(CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NC[C@@H]5COCCO5)c([N+](=O)[O-])c4)c(Oc4cnc5[nH]ccc5c4)c3)CC2)C1
InChIKey: SEOFRNNPVLILNV-OCUJDILZSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Bcl-2/Bcl-X TR-FRET Assay: Compounds disclosed herein were tested for blocking of Bcl-2/Bcl-X protein with its ligand in an assay based on Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) methodology. Recombinant human 0.05 nM Bcl-2/0.03 nM Bcl-X protein was pre-incubated with a serial dilution of compounds disclosed herein (maximum concentration is 0.1 μM for Bcl-2 assay, and 10 μM for Bcl-xl assay, 3-fold serially diluted, 10 points; or maximum concentration is 0.02 μM for Bcl-2 assay, and 2 μM for Bcl-xl assay, 3-fold serially diluted, 10 points) at room temperature for 0.5 hour in an assay buffer containing 20 mM potassium phosphate buffer, pH 7.5, 50 mM NaCl, 1 mM EDTA, 0.05% Tween-20, 0.01% BSA. Then the FITC labeled Bak peptide Ac-GQVGRQLAIIGDK(FITC)INR-amide (0.5 nM for Bcl-2, 0.3 nM for Bcl-xl) and MAb Anti 6His Tb cryptate Gold were added to plate and further incubated at room temperature for 1 hour. The TR-FRET signals (337 nm-520 nm-490 nm) were read on BMG PHERAstar FSX instrument. The inhibition percentage of Bcl-2/Bcl-X interaction with its ligand in presence of increasing concentrations of compounds was calculated based on the TR-FRET signals. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Graphpad Prism software. To improve the assay sensitivity and test more potent compounds in the present application, the bcl-2 concentration was reduced in method B.
Measurement: IC50 = 0.038 nM (pChEMBL 10.420000076293945)
Descriptors: MW 864.04, ALogP 7.92, HBA 12, HBD 3, PSA 181.26, QED 0.08
Compound (SMILES): COc1ccc(NC(=O)OC[C@H]2COc3c(cc(Cl)c4nc(-c5cc(C)cc6nc(OC)cnc56)sc34)O2)cn1
InChIKey: GZRBIJYGDCLWCQ-OAHLLOKOSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of PXR (unknown origin)
Measurement: EC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 580.02, ALogP 5.67, HBA 11, HBD 1, PSA 126.81, QED 0.27
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2ccnc3[nH]ccc23)nc2c1ccn2S(C)(=O)=O
InChIKey: IJEDYDGSAXSVPY-GFCCVEGCSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of human IRAK4
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.48, ALogP 2.01, HBA 8, HBD 1, PSA 106, QED 0.55
Compound (SMILES): CCN(CCN)c1ccc(Nc2cc(NC3CC3)n3ncc(C#N)c3n2)cc1-n1cnnc1
InChIKey: VVIQQTQLDDARAW-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of human CDK7 expressed in HEK293 cells incubated for 2 hrs by NanoBRET assay
Measurement: IC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 443.52, ALogP 2.28, HBA 11, HBD 3, PSA 138.01, QED 0.36
Compound (SMILES): CC1(C)CC(=O)c2c(C(F)(F)F)nn(Cc3ccc(C(=O)NO)cc3)c2C1
InChIKey: AUEDMSVXWKXTGU-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of human recombinant HDAC7 using Boc-Lys(tri-fluoroacetyl)-AMC as substrate by fluorescence based analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 381.35, ALogP 3.22, HBA 5, HBD 2, PSA 84.22, QED 0.63
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCC3(CC2)CC(N2CCC[C@H]2c2ccccc2C2CC2)C3)cc1Oc1cnc2[nH]ccc2c1
InChIKey: IVXFXSGHRVGVIZ-WBCKFURZSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Bcl-2/Bcl-X Fluorescence Polarization Assay: Compounds disclosed herein were tested for blocking of Bcl-2/Bcl-xl protein with its ligand in an assay based on fluorescence polarization methodology. Recombinant human 2.7 nM Bcl-2/1.3 nM Bcl-xl protein was pre-incubated with a serial dilution of compounds disclosed herein (maximum concentration is 1 μM for Bcl-2 assay, and 10 μM or 1 μM for Bcl-xl assay, 3-fold serially diluted, 10 points) at room temperature for 0.5 hour in an assay buffer containing 20 ml potassium phosphate buffer, pH 7.5, 50 mM NaCl, 1 mM EDTA, 0.05% Tween-20, 0.01% BSA. Then the FITC labeled Bak peptide Ac-GQVGRQLAIIGDK (FITC)INR-amide (1 nM for Bcl-2, 0.82 nM for Bcl-xl) was added to plate and further incubated at room temperature for 0.5 h. The FP signals (485 nm-520 nm-520 nm) were read on BMG PHERAstar FS or BMG PHERAstar FSX instalment. The inhibition percentage of Bcl-2/Bcl-xl interaction with its ligand in presence of increasing concentrations of compounds was calculated based on the FP signals. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Graphpad Prism software.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 860.05, ALogP 8.68, HBA 11, HBD 3, PSA 172.03, QED 0.08
Compound (SMILES): CC[C@@]1(C(=O)O)C[C@H]1[C@H](N)C(=O)O.Cl
InChIKey: BGPCGYBGJFZOPY-CGOLMLKISA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35400
Assay: Agonist activity at rat mGluR7 receptor expressed in HEK293 cells by IP-1 HTRF assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 187.19, ALogP -0.1, HBA 3, HBD 3, PSA 100.62, QED 0.57
Compound (SMILES): CN1CCN(C(=O)c2cc(Br)cc([N+](=O)[O-])c2N[C@@H]2CCCC[C@@H]2NC(=O)c2cc(=O)[nH]c3c(F)cccc23)CC1
InChIKey: FZNWILPXXNKETO-YADHBBJMSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of human DPP-4 using Gly-Pro-AMC as substrate incubated for 10 mins by FRET-enzymatic assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 629.49, ALogP 3.88, HBA 7, HBD 3, PSA 140.68, QED 0.28
Compound (SMILES): NS(=O)(=O)c1c(CC2CCNCC2)ccc(-c2ccc(C3CCNCC3)cc2)c1-c1nn[nH]n1
InChIKey: LHOHTNKBXFSQBC-UHFFFAOYSA-N
Target: Metallo-beta-lactamase type 2 (SINGLE PROTEIN), Bacteria
UniProt: C7C422
Assay: Class B Enzyme Assay: The Class B enzyme activities were measured in the presence of the test inhibitor in a fluorescence assay against a commercially available substrate consisting of a cephalosporin core linking 7-hydroxycoumarin to fluorescein (CCF2-FA). The enzyme (NDM-1, IMP-1 or VIM-1) and the substrate were diluted in 100 mM KH2PO4 buffer (pH 7) containing 0.005% Tween-20 and 10 μM ZnSO4. In the assay, the final concentration of enzyme was 1 pM, 2 pM and 30 pM for NDM-1, IMP-1 and VIM-1, respectively, and the final concentration of CCF2-FA was 1.25 μM. The test inhibitor was dissolved in dimethylsulfoxide and diluted 1:50 in the assay, resulting in a final concentration range of 20 uM to 0.00063 uM. In a 384-well microplate, the test inhibitor was incubated with the metallo-β-lactamase enzyme and the substrate for 2 hours at 25° C. Fluorescence at 460 nm following excitation at 405 nm was measured. The IC50 value was determined from semi-logarithmic plots of enzyme inhibition versus inhibitor concentration, with a curve generated using a 4-parameter fit.
Measurement: IC50 = 4.58 nM (pChEMBL 8.34000015258789)
Descriptors: MW 481.63, ALogP 2.19, HBA 7, HBD 4, PSA 138.68, QED 0.42
Compound (SMILES): NS(=O)(=O)c1c(C(F)(F)F)ccc(-c2ccc(C3CCN(CC4CNC4)CC3)cc2)c1-c1nn[nH]n1
InChIKey: OASRXZZSPMUCKN-UHFFFAOYSA-N
Target: Metallo-beta-lactamase type 2 (SINGLE PROTEIN), Bacteria
UniProt: C7C422
Assay: Class B Enzyme Assay: The Class B enzyme activities were measured in the presence of the test inhibitor in a fluorescence assay against a commercially available substrate consisting of a cephalosporin core linking 7-hydroxycoumarin to fluorescein (CCF2-FA). The enzyme (NDM-1, IMP-1 or VIM-1) and the substrate were diluted in 100 mM KH2PO4 buffer (pH 7) containing 0.005% Tween-20 and 10 μM ZnSO4. In the assay, the final concentration of enzyme was 1 pM, 2 pM and 30 pM for NDM-1, IMP-1 and VIM-1, respectively, and the final concentration of CCF2-FA was 1.25 μM. The test inhibitor was dissolved in dimethylsulfoxide and diluted 1:50 in the assay, resulting in a final concentration range of 20 uM to 0.00063 uM. In a 384-well microplate, the test inhibitor was incubated with the metallo-β-lactamase enzyme and the substrate for 2 hours at 25° C. Fluorescence at 460 nm following excitation at 405 nm was measured. The IC50 value was determined from semi-logarithmic plots of enzyme inhibition versus inhibitor concentration, with a curve generated using a 4-parameter fit.
Measurement: IC50 = 4.13 nM (pChEMBL 8.380000114440918)
Descriptors: MW 521.57, ALogP 2.6, HBA 7, HBD 3, PSA 129.89, QED 0.45
Compound (SMILES): CN(C)CCNC=C1C(=O)CC(c2c(Cl)c(Cl)cc3[nH]ccc23)CC1=O
InChIKey: PZZMLUYOSFDDHG-RAXLEYEMSA-N
Target: Gamma-aminobutyric acid receptor-associated protein (SINGLE PROTEIN), Homo sapiens
UniProt: O95166
Assay: Inhibition of GABARAP (unknown origin) by Alphascreen assay
Measurement: IC50 = 4440 nM (pChEMBL 5.349999904632568)
Descriptors: MW 394.3, ALogP 3.53, HBA 4, HBD 2, PSA 65.2, QED 0.46
Compound (SMILES): CC(C)c1ccccc1[C@@H]1CCCN1C1CC2(CCN(c3ccc(C(=O)NS(=O)(=O)c4ccc(NC[C@@H]5COCCO5)c([N+](=O)[O-])c4)c(Oc4cnc5[nH]ccc5c4)c3)CC2)C1
InChIKey: SEOFRNNPVLILNV-OCUJDILZSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Bcl-2/Bcl-X TR-FRET Assay: Compounds disclosed herein were tested for blocking of Bcl-2/Bcl-X protein with its ligand in an assay based on Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) methodology. Recombinant human 0.05 nM Bcl-2/0.03 nM Bcl-X protein was pre-incubated with a serial dilution of compounds disclosed herein (maximum concentration is 0.1 μM for Bcl-2 assay, and 10 μM for Bcl-xl assay, 3-fold serially diluted, 10 points; or maximum concentration is 0.02 μM for Bcl-2 assay, and 2 μM for Bcl-xl assay, 3-fold serially diluted, 10 points) at room temperature for 0.5 hour in an assay buffer containing 20 mM potassium phosphate buffer, pH 7.5, 50 mM NaCl, 1 mM EDTA, 0.05% Tween-20, 0.01% BSA. Then the FITC labeled Bak peptide Ac-GQVGRQLAIIGDK(FITC)INR-amide (0.5 nM for Bcl-2, 0.3 nM for Bcl-xl) and MAb Anti 6His Tb cryptate Gold were added to plate and further incubated at room temperature for 1 hour. The TR-FRET signals (337 nm-520 nm-490 nm) were read on BMG PHERAstar FSX instrument. The inhibition percentage of Bcl-2/Bcl-X interaction with its ligand in presence of increasing concentrations of compounds was calculated based on the TR-FRET signals. The IC50 for each compound was derived from fitting the data to the four-parameter logistic equation by Graphpad Prism software. To improve the assay sensitivity and test more potent compounds in the present application, the bcl-2 concentration was reduced in method B.
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 864.04, ALogP 7.92, HBA 12, HBD 3, PSA 181.26, QED 0.08
Compound (SMILES): COc1ccc(NC(=O)OC[C@H]2COc3c(cc(Cl)c4nc(-c5cc(C)cc6nc(OC)cnc56)sc34)O2)cn1
InChIKey: GZRBIJYGDCLWCQ-OAHLLOKOSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 80000 nM (pChEMBL 4.0970001220703125)
Descriptors: MW 580.02, ALogP 5.67, HBA 11, HBD 1, PSA 126.81, QED 0.27
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2ccnc3[nH]ccc23)nc2c1ccn2S(C)(=O)=O
InChIKey: IJEDYDGSAXSVPY-GFCCVEGCSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of human Aurora B
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.48, ALogP 2.01, HBA 8, HBD 1, PSA 106, QED 0.55