lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccccc1-c1cnccc1C(=O)Nc1nnc(OCc2ccc(Cl)cc2)s1
InChIKey: ZAEYDSHIXXLWTJ-UHFFFAOYSA-N
Target: DNA polymerase theta (SINGLE PROTEIN), Homo sapiens
UniProt: O75417
Assay: Inhibition of DNA polymerase theta (unknown origin) ATPase activity incubated for 60 mins in presence of ATP by ADP-glo kinase assay
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 452.92, ALogP 5.09, HBA 7, HBD 1, PSA 86.23, QED 0.42
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2cccc(Nc3ccc4c(-c5cn[nH]c5)n[nH]c4c3)c2)n(-c2ccc(F)cc2)n1
InChIKey: UQSQJOQPNAARFP-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of wild type TRKB (unknown origin) using TK peptide as substrate incubated for 30 mins in presence of ATP by HTRF analysis
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 549.61, ALogP 6.96, HBA 6, HBD 5, PSA 128.34, QED 0.15
Compound (SMILES): COc1ccc2c(N3C[C@@H](Cl)[C@@H]4OC[C@@H](OCc5ccccc5)[C@@H]43)ncnc2c1OC
InChIKey: SQXUDQUNSOWLGK-LMQGHGSNSA-N
Target: Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q14123
Assay: Inhibition of PDE1C (unknown origin) using [3H]-cAMP as substrate incubated for 1 hr by SPA assay
Measurement: IC50 = 573 nM (pChEMBL 6.239999771118164)
Descriptors: MW 441.92, ALogP 3.43, HBA 7, HBD 0, PSA 65.94, QED 0.54
Compound (SMILES): COc1ccc2c(c1)c[n+](CCO)c1ccc(F)cc21.[Br-]
InChIKey: ZBKGDGWEQRMRGD-UHFFFAOYSA-M
Target: Protein phosphatase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P35813
Assay: Inhibition of recombinant human PPM1A using pNPP as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by absorbance based assay
Measurement: IC50 = 1190 nM (pChEMBL 5.920000076293945)
Descriptors: MW 272.3, ALogP 2.42, HBA 2, HBD 1, PSA 33.34, QED 0.59
Compound (SMILES): CN(C(=O)[C@H](Cc1ccccc1Cl)NC(=O)[C@@H](NC(=O)c1cccs1)C(C)(C)C)N(C#N)Cc1cccc(Cl)c1F
InChIKey: KVMJONNVSMEASA-WIOPSUGQSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of cathepsin B (unknown origin) using Z-Arg-Arg-pNA as substrate incubated for 60 mins
Measurement: Ki = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 618.56, ALogP 5.42, HBA 6, HBD 2, PSA 105.54, QED 0.18
Compound (SMILES): NS(=O)(=O)c1ccc(COc2ccc3ccc(=O)oc3c2)cc1
InChIKey: PJSAGAAMVQKOJV-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant CA4 assessed as inhibition constant incubated for 45 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 46.7 nM (pChEMBL 7.329999923706055)
Descriptors: MW 331.35, ALogP 2.02, HBA 5, HBD 1, PSA 99.6, QED 0.74
Compound (SMILES): NC(=O)NCCSc1nnc(-c2ccc3c(c2)nc(CN2CCC(c4cccc(OCc5ccc(Cl)cc5F)n4)CC2)n3C[C@@H]2CCO2)[nH]1
InChIKey: XBTYMLUAYWLUCT-VWLOTQADSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at GLP-1R (unknown origin) transfected in HEK293 cells assessed as beta-arrestin2 recruitment incubated for 5 mins by Envision multiplate reader analysis
Measurement: EC50 = 349 nM (pChEMBL 6.460000038146973)
Descriptors: MW 706.25, ALogP 5.52, HBA 10, HBD 3, PSA 149.1, QED 0.11
Compound (SMILES): Cc1cccc(-c2ccc(-c3cc4cnc(NCCCN5CCCC5=O)nc4n(CCCCN)c3=O)c(Cl)c2)n1
InChIKey: JKMPPFJOKQMACK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 26 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P289
Assay: Inhibition of MST4 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay
Measurement: EC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 560.1, ALogP 4.65, HBA 8, HBD 2, PSA 119.03, QED 0.26
Compound (SMILES): COc1cc(NC(=O)c2cc(=O)c3ccccc3o2)c(C(=O)Nc2ccc(N3CCN(Cc4cccc(-c5cccnc5)c4)CC3)cc2)cc1OC
InChIKey: MSBZSKADPXRCSH-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human Hepatocyte using Luciferin-IPA as substrate
Measurement: IC50 = 609 nM (pChEMBL 6.210000038146973)
Descriptors: MW 695.78, ALogP 6.7, HBA 9, HBD 2, PSA 126.24, QED 0.16
Compound (SMILES): O=C(OCCCCn1cccc1C(=O)c1ccccc1Cl)c1ccccc1
InChIKey: NURQWTJKNLREAR-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2 receptor expressed in HEK293 cell membrane incubated for 90 mins by competition binding assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 381.86, ALogP 5.01, HBA 4, HBD 0, PSA 48.3, QED 0.31
Compound (SMILES): Cc1ccc(O)c(C)c1-n1c(N)c(C(=O)N2CCn3nccc3C2)c2nc(C3CC3)c(C)nc21
InChIKey: SJUCQFPJGCKBQX-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1 phosphorylation at Thr14 residue in human HCC1569 cells incubated for 6 hrs by Western blot analysis
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 457.54, ALogP 3.36, HBA 8, HBD 2, PSA 115.09, QED 0.49
Compound (SMILES): Cc1nnc2c(NCCCCNC(=O)OC(C)(C)C)nc3ccccc3n12
InChIKey: MFTRLHOLYPZODT-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Evaluation of BRD4 binding inhibition ability: The following experiment was performed to evaluate the ability of [1,2,4]triazolo[4,3-a]quinoxaline derivative of the present invention to inhibit the interaction between BRD4 (BD1+BD2) bromodomain, one of BET protein family, and tetraacetylated histone H4 peptide.The compound was serially diluted at the ratio of 1:5 in assay buffer from 10 mM stock in DMSO (initial concentration: 100 μM) on white OptiPlate-384 (PerkinElmer). A mixture comprising 100 nM GST-BRD4 (BD1+BD2) and 100 nM biotinylated acetyl-histone H4 (Lys5,8,12,16) peptide was prepared in assay buffer (50 mM HEPES pH 7.4; 25 mM NaCl; 0.05% Tween 20; 0.1% bovine serum albumin (BSA); 10 mM dithiothreitol (DTT)). After adding 6 μl of the mixture to the diluent, 6 μl of the pre-mixed AlphaLISA Glutathione Acceptor Beads and AlphaScreen Streptavidin Donor Beads (PerkinElmer, 10 μg/ml in assay buffer, respectively) was added thereto. The samples were incubated in the dark at room temperature for 30 minutes (shaking at 300 rpm). Then, the signals were measured with PerkinElmer Envision HTS Multilabel Reader using an alpha screen protocol of PerkinElmer. Each plate contained the negative control in which biotinylated acetyl-histone H4 peptide and GST-BRD4 (BD1+BD2) were replaced by assay buffer. In the case of using the software GraphPad Prism for calculation, the negative control point was input as a low standard value. The positive control (probe molecule l-BET762 containing protein/peptide mixture) proceeded to pipetting. IC50 value was determined by using GraphPad Prism 3.03 software (or an updated version thereof).
Measurement: IC50 = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 370.46, ALogP 3.3, HBA 7, HBD 2, PSA 93.44, QED 0.65
Compound (SMILES): CCCCCn1cccc1C(=O)c1ccc(C)cc1
InChIKey: HFGMLGJMJLNXAA-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2 receptor expressed in HEK293 cell membrane incubated for 90 mins by competition binding assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 255.36, ALogP 4.22, HBA 2, HBD 0, PSA 22, QED 0.56
Compound (SMILES): C/C(=N\OC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1Cl)c1ccccc1Br
InChIKey: DJKDHAGGJFEMAU-DNTJNYDQSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 incubated for 15 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 32.8 nM (pChEMBL 7.480000019073486)
Descriptors: MW 466.14, ALogP 3.98, HBA 5, HBD 1, PSA 98.82, QED 0.42
Compound (SMILES): N#C[C@@H]1CC(F)(F)CN1C(=O)CNC(=O)c1ccnc2ccc(OC[C@H](O)[C@@H](O)CF)cc12
InChIKey: BIEPKNNSCPIQDM-IGNZVWTISA-N
Target: Dipeptidyl peptidase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6V1X1
Assay: Inhibition of DPP8 (unknown origin) using Ala-Pro-paranitroanilide as chromogenic substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 466.42, ALogP 0.79, HBA 7, HBD 3, PSA 135.78, QED 0.52
Compound (SMILES): CC(=O)N1CCc2c(c(N3CCCc4cc(-c5cnn(C)c5)c(C(F)F)cc43)nn2[C@H]2CC[C@H](CN3Cc4cc5c(cc4C3)C(=O)N(C3CCC(=O)NC3=O)C5=O)CC2)C1
InChIKey: NORRDWRSNUOCBV-XCIZWWPASA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin) preincubated with compound for 5 mins followed by NADPH addition and measured after 5 mins by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 819.91, ALogP 5.36, HBA 11, HBD 1, PSA 145.98, QED 0.24
Compound (SMILES): C[C@H](Nc1nccc(N2C(=O)OC[C@@H]2[C@@H](C)OC(C)(C)C)n1)c1ccc(-c2ccc(NC(=O)COc3cccnc3)cc2)cc1
InChIKey: CMSLMETZNCRLFZ-QFWOEDSFSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Inhibition of NAMPT (unknown origin)
Measurement: IC50 = 51.43 nM (pChEMBL 7.289999961853027)
Descriptors: MW 610.71, ALogP 6.26, HBA 9, HBD 2, PSA 127.8, QED 0.2
Compound (SMILES): CCC(c1nn(-c2cccnc2)c2cc(Cl)ccc12)n1nc(C)c2c(N)ncnc21
InChIKey: YHRHHMKECWHDJH-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using PIP2:PS as substrate measured after 1 hrs in presence of by ADP-Glo Kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 418.89, ALogP 4.1, HBA 8, HBD 1, PSA 100.33, QED 0.47
Compound (SMILES): N#Cc1ccc2cc1OC/C=C\CNc1ncc(C(=O)NC3CCN(CC4CCOCC4)CC3)c(n1)N2
InChIKey: NQSLOMAYSOUYFR-UPHRSURJSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of MERTK (unknown origin) expressed in HEK293 cells by MCE assay
Measurement: IC50 = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 503.61, ALogP 3.07, HBA 9, HBD 3, PSA 124.43, QED 0.54
Compound (SMILES): COc1ccc(C2COc3cc(OCc4c(C)cc(C)cc4C)ccc3C2=O)cc1
InChIKey: RNPMBRVHVZNARZ-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Inhibition of human TRPV4 by whole-cell patch clamp method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 402.49, ALogP 5.56, HBA 4, HBD 0, PSA 44.76, QED 0.56
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2ccc(-c3cn(CCCCC4CN(CCCCC(=O)Nc5cccc6c5CN(C5CCC(=O)NC5=O)C6=O)N=N4)c4ncnc(N)c34)cc2)no1
InChIKey: LVPQPNLLAWYWCR-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Mus musculus
UniProt: Q00342
Assay: Inhibition of FLT3 ITD/F691L mutant in mouse BaF3 cells
Measurement: IC50 = 116 nM (pChEMBL 6.940000057220459)
Descriptors: MW 857.98, ALogP 6.4, HBA 14, HBD 5, PSA 247.43, QED 0.06
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2cccc(Nc3ccc4c(-c5cn[nH]c5)n[nH]c4c3)c2)n(-c2ccc(F)c(F)c2)n1
InChIKey: JZORFWRZZRNPER-UHFFFAOYSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of wild type TRKC (unknown origin) using TK peptide as substrate incubated for 30 mins in presence of ATP by HTRF analysis
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 567.6, ALogP 7.1, HBA 6, HBD 5, PSA 128.34, QED 0.15
Compound (SMILES): CC(=O)N[C@H]1Cc2ccc(cc2)OCCCC[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)c2nc3ccccc3s2)NC(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: RJBLHAMXODQZMM-YDPTYEFTSA-N
Target: Suppressor of tumorigenicity 14 protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y6
Assay: Inhibition of N-terminal Met/6His tagged human recombinant matriptase catalytic domain (Gly596 to Val855 residues) using Boc-QAR-AMC as substrate preincubated for 30 mins followed by substrate addition and measured by fluorescence based analysis
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 754.91, ALogP 2.75, HBA 9, HBD 7, PSA 217.49, QED 0.05
Compound (SMILES): CCS(=O)(=O)Nc1cc(-c2cc(NC3CN(C(=O)CN4CCOCC4)C3)c(=O)n(C)c2)cc2c1ccn2C(C)(c1ccccn1)c1ccccn1
InChIKey: LBZGKECCBYGEHP-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of N-terminal his6-tagged human BRD4 BD2 incubated for 15 mins by TR-FRET assay
Measurement: IC50 = 486.4 nM (pChEMBL 6.309999942779541)
Descriptors: MW 710.86, ALogP 3.33, HBA 11, HBD 2, PSA 143.69, QED 0.21
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(-c2ncc(CNc3ccccc3)s2)cc1
InChIKey: RBVOLVRZLYKTAA-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of human recombinant HDAC7 using Ac-Leu-Gly-Lys (Tfa)-AMC as substrate preincubated with compound for 10 mins followed by substrate addition and measured after 45 mins by TECAN microtiter plate reader analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 400.51, ALogP 5.26, HBA 5, HBD 3, PSA 80.04, QED 0.39
Compound (SMILES): COc1cnc2c(-c3nc4ccc5c(c4s3)OC[C@H](COC(=O)Nc3cnc(C)nc3)O5)cc(C)cc2n1
InChIKey: LVYZBDLUUNXTHZ-MRXNPFEDSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes
Measurement: IC50 > 6000 nM (pChEMBL 5.2220001220703125)
Descriptors: MW 530.57, ALogP 4.71, HBA 11, HBD 1, PSA 130.47, QED 0.34
Compound (SMILES): C[C@@H]1NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](Cc2c[nH]c3ccccc23)NC(=O)CSC[C@@H](C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC1=O
InChIKey: VPDNRKHEKKMOBV-UDVPIEQESA-N
Target: Methylcytosine dioxygenase TET3 (SINGLE PROTEIN), Homo sapiens
UniProt: O43151
Assay: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay
Measurement: IC50 = 3548.13 nM (pChEMBL 5.449999809265137)
Descriptors: MW 1998.21
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)O/N=C/c2ccc(OCc3ccccc3)cc2)c(Cl)cc1Cl
InChIKey: APKRUFZWCXUXRY-BRJLIKDPSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA12 incubated for 15 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 199 nM (pChEMBL 6.699999809265137)
Descriptors: MW 479.34, ALogP 4.41, HBA 6, HBD 1, PSA 108.05, QED 0.31
Compound (SMILES): N#Cc1ccc2cc1OC/C=C\CNc1ncc(C(=O)NC3CCNCC3)c(n1)N2
InChIKey: SKHIHHSSPXZOHA-UPHRSURJSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of MERTK (unknown origin) expressed in HEK293 cells by MCE assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 405.46, ALogP 1.93, HBA 8, HBD 4, PSA 123.99, QED 0.56
Compound (SMILES): O=C(c1ccccc1Cl)c1cccn1CC12CC3CC(CC(C3)C1)C2
InChIKey: TZAYRALGHBBCCI-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2 receptor expressed in HEK293 cell membrane assessed as inhibition constant incubated for 90 mins by competition binding assay
Measurement: Ki = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 353.89, ALogP 5.59, HBA 2, HBD 0, PSA 22, QED 0.66
Compound (SMILES): N#Cc1ccc(CN2CCC(Nc3c(-c4cc[nH]n4)cnc4[nH]ccc34)CC2)cc1
InChIKey: QSHVZAGPZCYJAM-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hrs by TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 397.49, ALogP 3.9, HBA 5, HBD 3, PSA 96.42, QED 0.47
Compound (SMILES): CN(C(=O)[C@H](Cc1ccccc1F)NC(=O)[C@@H](NC(=O)c1cccs1)C(C)(C)C)N(C#N)Cc1cccc(Cl)c1F
InChIKey: UNICQUXWGGDNLF-WIOPSUGQSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Inhibition of recombinant human cathepsin S using Z-Phe-Arg-AMC as substrate incubated for 60 mins
Measurement: Ki = 8.01 nM (pChEMBL 8.100000381469727)
Descriptors: MW 602.11, ALogP 4.91, HBA 6, HBD 2, PSA 105.54, QED 0.2
Compound (SMILES): CCCCCc1ccc(-c2cc(O)cc(=O)[nH]2)cc1
InChIKey: FGXQPGLJMDLYGF-UHFFFAOYSA-N
Target: G-protein coupled receptor 84 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQS5
Assay: Agonist activity at GPR84 (unknown origin) expressed in HEK293T cells expressing beta-arrestin 2-nanoluciferase incubated for 5 mins by beta-arrestin recruitment based BRET assay
Measurement: EC50 = 2630.27 nM (pChEMBL 5.579999923706055)
Descriptors: MW 257.33, ALogP 3.48, HBA 2, HBD 2, PSA 53.09, QED 0.81
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)CSC[C@@H](C(N)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CS)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@@H]2CCCN2C1=O
InChIKey: HWBJMURCMNTDLJ-ZNZOAAGHSA-N
Target: Methylcytosine dioxygenase TET3 (SINGLE PROTEIN), Homo sapiens
UniProt: O43151
Assay: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay
Measurement: IC50 = 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 2138.51
Compound (SMILES): O=C(Nc1cccc(CO)c1)c1cccn1Cc1ccc(F)cc1
InChIKey: RYCTYVZOVFRZQR-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2 receptor expressed in HEK293 cell membrane assessed as inhibition constant incubated for 90 mins by competition binding assay
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 324.36, ALogP 3.42, HBA 3, HBD 2, PSA 54.26, QED 0.76
Compound (SMILES): Cc1cc(C)cc(Nc2nccc(-c3cc(C(=O)N[C@@H](C)CN4CCCC4)n(C)n3)n2)c1
InChIKey: FOOBTRPSYPGQSN-SFHVURJKSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) incubated for 60 mins in presence of ATP by KinaseGlo assay
Measurement: IC50 = 173 nM (pChEMBL 6.760000228881836)
Descriptors: MW 433.56, ALogP 3.45, HBA 7, HBD 2, PSA 87.97, QED 0.59
Compound (SMILES): NS(=O)(=O)c1ccc(CCN(Cc2cccc(OCC(=O)O)c2)S(=O)(=O)c2ccc(Cl)cc2)cc1
InChIKey: VLSUJPZNHYSAPC-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 244 nM (pChEMBL 6.610000133514404)
Descriptors: MW 539.03, ALogP 2.88, HBA 6, HBD 2, PSA 144.07, QED 0.38
Compound (SMILES): NS(=O)(=O)c1ccc(CCN(Cc2cccc(NCC(=O)O)c2)S(=O)(=O)c2cc(Cl)ccc2Cl)cc1
InChIKey: HDZDBBPCPFBOFS-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 36.9 nM (pChEMBL 7.429999828338623)
Descriptors: MW 572.49, ALogP 3.57, HBA 6, HBD 3, PSA 146.87, QED 0.32
Compound (SMILES): CS(=O)(=O)C[C@H]1CN(C2CCN(c3cc(Cl)ccn3)CC2)[C@@H](Cc2ccc(Cl)cc2)CO1
InChIKey: IBYFODJPVIGQDW-FCHUYYIVSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Inhibition of human C-terminal His tagged AMCase expressed in CHO-K1 cells using 4-methylumbelliferyl beta-D-N,N'-diacetylchitobioside hydrate as substrate incubated for 60 mins by fluorometric assay
Measurement: IC50 = 554 nM (pChEMBL 6.260000228881836)
Descriptors: MW 498.48, ALogP 3.71, HBA 6, HBD 0, PSA 62.74, QED 0.61
Compound (SMILES): O=C(NC12CC3CC(CC(C3)C1)C2)c1cccn1Cc1ccc(F)cc1
InChIKey: IPNYVNZECJJLDV-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2 receptor expressed in HEK293 cell membrane assessed as inhibition constant incubated for 90 mins by competition binding assay
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 352.45, ALogP 4.37, HBA 2, HBD 1, PSA 34.03, QED 0.87
Compound (SMILES): N#Cc1c(O)nc(SCC(=O)Nc2ccc(S(N)(=O)=O)cc2)nc1-c1ccc(Cl)c(Cl)c1
InChIKey: RSUIEUWUPPVSIR-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 assessed as inhibition constant preincubated for 15 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 510.38, ALogP 3.41, HBA 8, HBD 3, PSA 159.06, QED 0.34
Compound (SMILES): COc1cc(SC(F)F)c(OC)cc1CCN.Cl
InChIKey: YSVOKVXGNSOLHC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]LSD from human 5-HT2B receptor expressed in HEK293 cell membrane incubated for 90 mins by microbeta liquid scintillation counting method
Measurement: Ki = 23.44 nM (pChEMBL 7.630000114440918)
Descriptors: MW 263.31, ALogP 2.52, HBA 4, HBD 1, PSA 44.48, QED 0.8
Compound (SMILES): COC(=O)C1(NC(=O)N[C@]2(C)CC[C@]3(C)CC[C@]4(C)C5=CC=C6C(=CC(=O)C(O)=C6C)[C@]5(C)CC[C@@]4(C)[C@@H]3C2)CCC1
InChIKey: VRZYWQDMGPXURI-ZIMIRHEFSA-N
Target: Peroxiredoxin-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13162
Assay: Inhibition of recombinant PRDX4 (unknown origin) using H2O2 as substrate preincubated for 0.5 hrs followed by substrate addition by TRX-TrxR-NADPH coupling assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 576.78, ALogP 6.76, HBA 5, HBD 3, PSA 104.73, QED 0.32
Compound (SMILES): Cc1cccc(-c2ccc(-c3cc4cnc(NCCCN5CCOCC5)nc4n(CCCCN)c3=O)c(Cl)c2)n1
InChIKey: LPNYPGSVVFRVQQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase SIK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H0K1
Assay: Inhibition of SIK2 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 20 hrs by NanoBRET assay
Measurement: EC50 = 512 nM (pChEMBL 6.289999961853027)
Descriptors: MW 562.12, ALogP 4.36, HBA 9, HBD 2, PSA 111.19, QED 0.26
Compound (SMILES): O=C(NCCO)[C@@H]1Cc2ccccc2CN1C(=O)c1ccc(O)cc1
InChIKey: LJMIZTSHKOKOFB-KRWDZBQOSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2 receptor expressed in HEK293 cell membrane assessed as inhibition constant incubated for 90 mins by competition binding assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 340.38, ALogP 1.07, HBA 4, HBD 3, PSA 89.87, QED 0.78
Compound (SMILES): CN1C(=O)C(=Cc2ccc(S(N)(=O)=O)cc2)C(=O)N(C)C1=O
InChIKey: UNJOGMGWOARMQT-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase IX assessed as inhibition constant incubated for 15 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 323.33, ALogP -0.23, HBA 5, HBD 1, PSA 117.85, QED 0.6
Compound (SMILES): NS(=O)(=O)c1ccc(CN(Cc2cccc(OCC(=O)O)c2)S(=O)(=O)c2ccccc2)cc1
InChIKey: SVJFIIMJBUFFGC-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 490.56, ALogP 2.19, HBA 6, HBD 2, PSA 144.07, QED 0.44
Compound (SMILES): CN(C)C1CN(Cc2ccc(NC(=O)c3ccc(OCCC(F)(F)F)c([N+](=O)[O-])c3)cc2C(F)(F)F)C1
InChIKey: KLHLSKWJVKEYCK-UHFFFAOYSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 3CL protease using Dabcyl-KTSAVLQSGFRKME-Edans as fluorogenic substrate pre-incubated with compound for 30 mins followed by substrate addition by FRET assay
Measurement: IC50 = 38270 nM (pChEMBL 4.420000076293945)
Descriptors: MW 534.46, ALogP 4.94, HBA 6, HBD 1, PSA 87.95, QED 0.28
Compound (SMILES): Cc1cc(C#N)ncc1Oc1cc(Nc2ccc(N3CCOCC3)cn2)c2ncn(C)c2n1
InChIKey: UEFBECCKJTVZES-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of N-terminal His-tagged recombinant human JAK3 (795 to 1124 residues) expressed in Sf21 cells using polyGT as substrate incubated for 45 mins in presence of ATP by Topcount method
Measurement: IC50 = 494 nM (pChEMBL 6.309999942779541)
Descriptors: MW 442.48, ALogP 3.31, HBA 10, HBD 1, PSA 114.01, QED 0.5
Compound (SMILES): CCN(CC)CCNC(=O)[C@H]1CC[C@H](NC(=O)c2cnc3nc2Nc2ccc(C)c(c2)OC/C=C\CN3)CC1
InChIKey: UEMPFKOYBHCUIG-QVIWBNHYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of MERTK (unknown origin) expressed in HEK293 cells by MCE assay
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 535.69, ALogP 3.64, HBA 8, HBD 4, PSA 120.51, QED 0.38
Compound (SMILES): Cc1cc2ccc(OCc3ccc(S(N)(=O)=O)cc3)cc2oc1=O
InChIKey: KDMKQNJDFWYSKD-UHFFFAOYSA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Inhibition of human recombinant CA5A assessed as inhibition constant incubated for 45 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 345.38, ALogP 2.33, HBA 5, HBD 1, PSA 99.6, QED 0.73
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CCC3(CC2)CC(N2CCC[C@H]2c2ccccc2Cl)C3)cc1Oc1cnc2[nH]ccc2c1
InChIKey: ORZUFNOOMDCXOS-KDXMTYKHSA-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 = 0.31 nM (pChEMBL 9.510000228881836)
Descriptors: MW 854.43, ALogP 8.46, HBA 11, HBD 3, PSA 172.03, QED 0.08
Compound (SMILES): Nc1nc2c(ncn2[C@@H]2C[C@H](COCCP(=O)(O)O)N(C(=O)CCP(=O)(O)O)C2)c(=O)[nH]1
InChIKey: APDUDHYPFAMPGN-NXEZZACHSA-N
Target: Xanthine-guanine phosphoribosyltransferase (SINGLE PROTEIN), Escherichia coli (strain K12)
UniProt: P0A9M5
Assay: Binding affinity to Escherichia coli XGPRT by spectrophotometry
Measurement: Ki = 1000 nM (pChEMBL 6)
Descriptors: MW 494.34, ALogP -1.39, HBA 9, HBD 6, PSA 234.19, QED 0.17
Compound (SMILES): CCCC(CCC)c1nc2c(Nc3ccc(C#CCCCCCCCCN)cc3)nc3ccccc3c2[nH]1
InChIKey: LFZSIMYZENEGOC-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Positive allosteric modulation of human A3 adenosine receptor transfected in HEK293 cell membranes assessed as potentiation of 5-(2-chloro-6-((3-iodobenzyl)amino)-9H-purin-9-yl)-3,4-dihydroxy-N-methyltetrahydrofuran-2-carboxamide induced [35S]GTP-gammaS binding by measuring agonist pEC50 at 0.001 uM pretreated for 1 hr followed by agonist addition and measured after 2 hrs by liquid scintillation counting method (Rvb = 7.41 +/- 0.09 No_unit)
Measurement: EC50 = 41.69 nM (pChEMBL 7.380000114440918)
Descriptors: MW 509.74, ALogP 8.58, HBA 4, HBD 3, PSA 79.62, QED 0.12
Compound (SMILES): CC[C@@H](C)[C@@H](NC(=O)c1cn(CCCCCF)c2ccccc12)C(=O)OC
InChIKey: USRIDQGNNQPOHX-DNVCBOLYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor stably transfected in AtT20 cells incubated for 60 mins by FLIPR membrane potential assay
Measurement: EC50 = 26.8 nM (pChEMBL 7.570000171661377)
Descriptors: MW 376.47, ALogP 4.1, HBA 4, HBD 1, PSA 60.33, QED 0.5
Compound (SMILES): C[C@@H](c1cnn(C)c1)n1cc(C(F)(F)F)cc(-c2cccc([C@]3(c4nncn4C)C[C@@H](C)C3)c2)c1=O
InChIKey: QRNMXYQPWPALPI-XOWTYJCDSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Inhibition of Cbl-b in CD3/CD28-stimulated human T cells assessed as increase in PLC-gamma1 phosphorylation at Tyr783 preincubated for 15 mins followed by CD3/CD28 stimulation measured after 1 hr by Western blot analysis
Measurement: EC50 = 610 nM (pChEMBL 6.210000038146973)
Descriptors: MW 496.54, ALogP 4.72, HBA 7, HBD 0, PSA 70.53, QED 0.4
Compound (SMILES): C=CC(=O)Nc1ccc(CN2C(=O)N(c3cc(OC)cc(OC)c3)Cc3cnc(Nc4ccccc4NC(=O)C=C)nc32)cc1
InChIKey: WPSQITLDKMIIOJ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 (450 to 758 residues) 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 = 466 nM (pChEMBL 6.329999923706055)
Descriptors: MW 605.66, ALogP 5.63, HBA 8, HBD 3, PSA 138.02, QED 0.19
Compound (SMILES): CC(=O)N[C@H](CCCN)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@@H]2CCCN2C1=O
InChIKey: OTVBXAWBCYIDNS-KFVILGJFSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Antagonist activity at C-terminal HA-tagged human MC3-R stably expressed in HEK293 cells co-expressing GScAMP22P cAMP reporter assessed as inhibition of alpha-MSH induced cAMP production by cell based luminescence assay
Measurement: IC50 = 498 nM (pChEMBL 6.300000190734863)
Descriptors: MW 1191.41
Compound (SMILES): CC(C)N(C)C(=O)c1cnc2nc1Nc1ccc(C#N)c(c1)OC/C=C\CN2
InChIKey: GVFZDWSYRPXQDB-PLNGDYQASA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of MERTK (unknown origin) expressed in HEK293 cells by MCE assay
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 378.44, ALogP 2.93, HBA 7, HBD 2, PSA 103.17, QED 0.77
Compound (SMILES): CN(C(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)C1CCCC1)C(C)(C)C)N(C#N)Cc1ccc(Cl)cc1
InChIKey: KNFARXVTOTYHMG-IZZNHLLZSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Inhibition of recombinant human cathepsin S using Z-Phe-Arg-AMC as substrate incubated for 60 mins
Measurement: Ki = 23.3 nM (pChEMBL 7.630000114440918)
Descriptors: MW 552.12, ALogP 4.45, HBA 5, HBD 2, PSA 105.54, QED 0.26
Compound (SMILES): Nc1nc(-c2ccco2)nc2c1nc(-c1ccco1)n2[C@@H]1OC[C@@H](O)[C@H]1O
InChIKey: JFKRMUAVFJYHNX-KGBXAXFASA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of radioligand I-AB-MECA from human adenosine A3 receptor expressed in CHO cell membrane incubated for 30 mins by microplate beta scintillation counting analysis
Measurement: Ki = 822 nM (pChEMBL 6.079999923706055)
Descriptors: MW 369.34, ALogP 1.18, HBA 10, HBD 3, PSA 145.59, QED 0.48
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)c2coc3ccccc3c2=O)cc1
InChIKey: JZNULZCLKROVLP-UHFFFAOYSA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Inhibition of human recombinant CA5A assessed as inhibition constant incubated for 45 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 46.3 nM (pChEMBL 7.329999923706055)
Descriptors: MW 344.35, ALogP 1.69, HBA 5, HBD 2, PSA 119.47, QED 0.75
Compound (SMILES): CCOc1ncc2cc(-c3ccc4c(c3)N3CCCC3CO4)c(=O)n(-c3ccc(OC(F)F)cc3)c2n1
InChIKey: LLNOSMJAMABNMK-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 31000 nM (pChEMBL 4.510000228881836)
Descriptors: MW 506.51, ALogP 4.81, HBA 8, HBD 0, PSA 78.71, QED 0.37
Compound (SMILES): Cl.O=C(CCc1ccco1)N[C@H]1CC[C@@]2(O)[C@H]3Cc4cccc5c4[C@@]2(CCN3CC2CC2)[C@H]1O5
InChIKey: MNPXBUYCRCAADV-HBILRMSKSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P33534
Assay: Agonist activity at mouse KOR expressed in CHO cells increase in [35S]GTPgammaS binding measured after 1.5 hrs by scintillation counter analysis
Measurement: EC50 = 441.8 nM (pChEMBL 6.360000133514404)
Descriptors: MW 448.56, ALogP 2.96, HBA 5, HBD 2, PSA 74.94, QED 0.71
Compound (SMILES): CO[C@]1(C(=O)N[C@H](C)c2ccc(-n3cc(F)cn3)nc2)CC[C@H](c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1
InChIKey: GBLBJPZSROAGMF-KFDHSVMUSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: RET V804L Gatekeeper Mutant Assay : In each well of a 384-well plate, 7.5 nM-10 nM of mutant RET (ProQinase 1096-0000-1) was incubated in a total of 12.5 μL of buffer (100 mM HEPES pH 7.5, 0.015% BriJ 35, 10 mM MgCl2, 1 mM DTT) with 1 μM CSKtide (FITC-AHA-KKKKDDIYFFFG-NH2) and 10 μM ATP at 25° C. for 120 minutes in the presence or absence of a dosed concentration series of compound (1% DMSO final concentration). The reaction was stopped by the addition of 70 μL of Stop buffer (100 mM HEPES pH 7.5, 0.015% Brij 35.35 mM EDTA and 0.2% of Coating Reagent 3 (Caliper Lifesciences)). The plate was then read on a Caliper EZReader 2 (protocol settings: −1.7 psi, upstream voltage −500, downstream voltage −3000, post sample sip 35s). Data was normalized to 0% and 100% inhibition controls and the IC50 calculated using a 4-parameter fit in the CORE LIMS.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 533.61, ALogP 4.2, HBA 9, HBD 3, PSA 135.53, QED 0.31
Compound (SMILES): CCCc1ccc(CCc2cc(O)cc(=O)[nH]2)cc1
InChIKey: HTNHXOPIEJQITI-UHFFFAOYSA-N
Target: G-protein coupled receptor 84 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQS5
Assay: Agonist activity at GPR84 (unknown origin) expressed in HEK293T cells expressing beta-arrestin 2-nanoluciferase incubated for 5 mins by beta-arrestin recruitment based BRET assay
Measurement: EC50 = 213.8 nM (pChEMBL 6.670000076293945)
Descriptors: MW 257.33, ALogP 2.82, HBA 2, HBD 2, PSA 53.09, QED 0.87
Compound (SMILES): CN1CCN(c2ccc(-c3cnc4ccc(/C=C5\SC(=O)NC5=O)nn34)cc2)CC1
InChIKey: UMMNIAUFUJLWSP-PDGQHHTCSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) by enzymatic assay
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 420.5, ALogP 2.47, HBA 8, HBD 1, PSA 82.84, QED 0.65
Compound (SMILES): COc1cc(-c2cnc3nc2NCCCNS(=O)(=O)c2cccc(c2)N3)ccc1F
InChIKey: QPDPAWXTOAVKLC-UHFFFAOYSA-N
Target: Ephrin type-A receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54764
Assay: Inhibition of full length EPHA4 (unknown origin) expressed in HEK293T cells using NanoBRET NanoGlo substrate incubated for 2 hrs in presence of K4 tracer by NanoBRET assay
Measurement: EC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 429.48, ALogP 3.13, HBA 7, HBD 3, PSA 105.24, QED 0.57
Compound (SMILES): CC(C)NC(=O)c1cnc2nc1Nc1ccc(N)c(c1)OC/C=C/CN2
InChIKey: OUOIQYPGNJQHIR-ONEGZZNKSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of MERTK (unknown origin) expressed in HEK293 cells by MCE assay
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 354.41, ALogP 2.3, HBA 7, HBD 4, PSA 114.19, QED 0.48
Compound (SMILES): Cc1ccc(-c2nc(SCC(=O)Nc3ccc(S(N)(=O)=O)cc3)nc(O)c2C#N)cc1
InChIKey: AIBZOXIWLFUJES-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 assessed as inhibition constant preincubated for 15 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 15.7 nM (pChEMBL 7.800000190734863)
Descriptors: MW 455.52, ALogP 2.41, HBA 8, HBD 3, PSA 159.06, QED 0.38
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(NC(=O)CCNC(=O)/C=C/c3cccnc3)cc2)n1
InChIKey: SFRNVAHAKLYGTH-UENHJXRBSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Inhibition of NAMPT (unknown origin)
Measurement: IC50 = 22.43 nM (pChEMBL 7.650000095367432)
Descriptors: MW 543.63, ALogP 4.18, HBA 8, HBD 3, PSA 138.44, QED 0.31
Compound (SMILES): COC(=O)c1c(OCc2ccc(S(N)(=O)=O)cc2)ccc2c(C)cc(=O)oc12
InChIKey: LYSZJQBPRRDXLZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Inhibition of human recombinant CA5A assessed as inhibition constant incubated for 45 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 17.7 nM (pChEMBL 7.75)
Descriptors: MW 403.41, ALogP 2.11, HBA 7, HBD 1, PSA 125.9, QED 0.51
Compound (SMILES): CCCNNC(=O)c1ccc(NC(=O)CCCCCCCn2cc(-c3cccnc3)nn2)cc1
InChIKey: IECGBOMSMXRDNX-UHFFFAOYSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Inhibition of N-terminal GST-tagged human recombinant NAMPT (2 to 491 residues) expressed in Escherichia coli expression system incubated for 30 mins by fluorescence based analysis
Measurement: IC50 = 2469 nM (pChEMBL 5.610000133514404)
Descriptors: MW 463.59, ALogP 3.96, HBA 7, HBD 3, PSA 113.83, QED 0.25
Compound (SMILES): N[C@H](C(=O)O)[C@H]1[C@@H](CO)[C@@H]1C(=O)O
InChIKey: CQOQGFPPQJNODN-STGXQOJASA-N
Target: Metabotropic glutamate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14832
Assay: Agonist activity at human recombinant mGluR3 receptor assessed as inhibition of forskolin-stimulated [3H]cAMP accumulation incubated for 20 mins by SPA kit analysis
Measurement: EC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 189.17, ALogP -1.66, HBA 4, HBD 4, PSA 120.85, QED 0.42
Compound (SMILES): CC1(C)CCN(c2cc(Cl)nc(OCCC(=O)O)n2)c2ccccc21
InChIKey: YHIRVAZNBUWSQH-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P28702
Assay: Partial agonist activity at full length human RXR beta transfected in HEK293T cells assessed as DR1 activation incubated for 16 hrs by Dual-glo luciferase assay
Measurement: EC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 361.83, ALogP 3.8, HBA 5, HBD 1, PSA 75.55, QED 0.82
Compound (SMILES): O=c1cc(-c2cn(Cc3ccc(F)cc3)c3ccccc23)oc2cc(O)cc(O)c12
InChIKey: ARBMYWNALBXGEJ-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of recombinant human ATXgamma using LPC16:0 as substrate measured every 60 sec for 50 mins by choline release assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 401.39, ALogP 5.01, HBA 5, HBD 2, PSA 75.6, QED 0.45
Compound (SMILES): C[C@H]1CN(C)CC[C@H]1c1cc(-c2ccncc2)c(-c2ccc(F)cc2)[nH]1.Cl.Cl
InChIKey: GZOOROPGDJTVTB-GMWJYZTKSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in HEK293 cells incubated for 30 mins by FluxOR dye based fluorescence analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 349.45, ALogP 4.94, HBA 2, HBD 1, PSA 31.92, QED 0.73
Compound (SMILES): O=S(=O)(Cc1ccccc1)Nc1c(F)cc(Oc2ncccc2-c2ccnc(N[C@@H]3CNC[C@@H](F)C3)n2)c(F)c1F
InChIKey: RBOAUACOQMQNBF-ROUUACIJSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Inhibition of IRE1alpha in human KMS-11 cells assessed as reduction in XBP1 splicing preincubated for 24 hrs followed by thapsigargin addition and measured after 30 mins by luminescence assay
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 588.59, ALogP 4.8, HBA 8, HBD 3, PSA 118.13, QED 0.19
Compound (SMILES): CN1CCC(NC(=O)[C@H]2CC[C@H](NC(=O)c3cnc4nc3Nc3ccc(C#N)c(c3)OC/C=C\CN4)CC2)CC1
InChIKey: UTPPAOMSIMPNEQ-UHCXJUERSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of MERTK (unknown origin) expressed in HEK293 cells by MCE assay
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 544.66, ALogP 2.95, HBA 9, HBD 4, PSA 144.3, QED 0.43
Compound (SMILES): Cn1cnc2c(Nc3cc(N)ncn3)cc(NC(C3CC3)C(F)(F)F)nc21
InChIKey: UXQRKLKOTWVRMI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of N-terminal His-tagged recombinant human JAK3 (795 to 1124 residues) expressed in Sf21 cells using polyGT as substrate incubated for 45 mins in presence of ATP by Topcount method
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 378.36, ALogP 2.84, HBA 8, HBD 3, PSA 106.57, QED 0.63
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(NCC2CCOCC2)c([N+](=O)[O-])c1)c1ccc(N2CC3(CC(CN4CCCC4c4ccccc4C4CC4)C3)C2)cc1Oc1cnc2[nH]ccc2c1
InChIKey: ASUKKSOJMDBKGX-UHFFFAOYSA-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 = 9004 nM (pChEMBL 5.050000190734863)
Descriptors: MW 846.02, ALogP 8.15, HBA 11, HBD 3, PSA 172.03, QED 0.07
Compound (SMILES): NS(=O)(=O)c1ccc(CN(Cc2cccc(OCC(=O)O)c2)S(=O)(=O)c2ccc(Br)cc2)cc1
InChIKey: LDKZSEHLTPVTOO-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 569.46, ALogP 2.95, HBA 6, HBD 2, PSA 144.07, QED 0.38
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=O)c2cc(-c3ccccc3O)n[nH]2)cc1
InChIKey: GUEJZWXGBCRYON-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA XII assessed as inhibition constant by stopped-flow CO2 hydrase assay method
Measurement: Ki = 188.5 nM (pChEMBL 6.71999979019165)
Descriptors: MW 386.43, ALogP 1.4, HBA 5, HBD 4, PSA 138.17, QED 0.51
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=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(=O)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)CCCCN)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)N[C@@H](CC(C)C)C(=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](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)C(C)C)[C@@H](C)O
InChIKey: UCZYGIOWULGKMQ-GDAVRZBZSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of 125I-Calcitonin from human CTR expressed in Baby hamster kidney cell membrane incubated for 120 mins by SPA method
Measurement: IC50 = 74.11 nM (pChEMBL 7.130000114440918)
Descriptors: MW 3971.41
Compound (SMILES): CNC[C@H](O)CN(C)Cc1ccccc1OCc1ccc(-c2nccs2)c(Cl)c1
InChIKey: UMKLFWMQTDMELK-SFHVURJKSA-N
Target: Protein arginine N-methyltransferase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA8
Assay: Inhibition of PRMT6 (unknown origin)
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 431.99, ALogP 4.05, HBA 6, HBD 2, PSA 57.62, QED 0.51
Compound (SMILES): CCOc1cccnc1Cc1ccc([C@H](F)C(=O)N[C@H](c2ccc(C)cc2)[C@@H](C)C(=O)O)cc1
InChIKey: BFXQKBUFKIVUSI-YWWLGCSWSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 464.54, ALogP 4.97, HBA 4, HBD 2, PSA 88.52, QED 0.44
Compound (SMILES): CN1CCN(Cc2ccc(NC(=O)c3cncc(C#Cc4cnc(N)nc4)c3)cc2C(F)(F)F)CC1
InChIKey: WXTPIRWETKOHAO-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET G810D mutant (unknown origin)
Measurement: IC50 = 1.47 nM (pChEMBL 8.829999923706055)
Descriptors: MW 495.51, ALogP 2.87, HBA 7, HBD 2, PSA 100.27, QED 0.54
Compound (SMILES): C=CC(=O)N1C[C@@H](n2nc(C#Cc3ccc4c(c3)nc(C(F)(F)F)n4C3CC3)c(C(N)=O)c2NC)C[C@@H]1COC
InChIKey: HXZKZGJKVZUSRL-ZWKOTPCHSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 V564F mutant (unknown origin) using 5-FAM-KKKKEEIYFFF-CONH2 peptide as fluorogenic substrate incubated for 80 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay
Measurement: IC50 = 295.3 nM (pChEMBL 6.53000020980835)
Descriptors: MW 555.56, ALogP 3.1, HBA 8, HBD 2, PSA 120.3, QED 0.34
Compound (SMILES): CCN1CCN(c2ccc(-c3cnc4ccc(/C=C5\SC(=O)NC5=O)nn34)cc2F)CC1
InChIKey: PUCCPIPNBMSAGL-UNOMPAQXSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) by enzymatic assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 452.52, ALogP 3, HBA 8, HBD 1, PSA 82.84, QED 0.61
Compound (SMILES): Cc1cc(S(C)(=O)=O)nc(F)c1Oc1cc(Nc2cc(N)ncn2)c2ncn(C)c2n1
InChIKey: FKNFARLKXXGKTK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of N-terminal His-tagged recombinant human JAK3 (795 to 1124 residues) expressed in Sf21 cells using polyGT as substrate incubated for 45 mins in presence of ATP by Topcount method
Measurement: IC50 = 127 nM (pChEMBL 6.900000095367432)
Descriptors: MW 444.45, ALogP 2.12, HBA 11, HBD 2, PSA 150.8, QED 0.44