lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C)CCNc1cc(F)cc(-c2cccc3[nH]c(-c4n[nH]c5ncc(-c6ccncc6)cc45)cc23)c1
InChIKey: RWXXQTJPPPDLKN-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant CLK2 (unknown origin) using Ser/Thr 6 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 491.57, ALogP 5.95, HBA 5, HBD 3, PSA 85.52, QED 0.26
Compound (SMILES): CC1N(S(=O)(=O)c2ccccc2)c2ccc(C(=O)NCc3ccccc3Cl)cc2C1(C)C
InChIKey: LFTWTAHUDUFFGU-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Antagonist activity at human GnRH receptor expressed in CHO-K1 cells assessed as inhibition of buserelin-induced response preincubated for 20 mins followed by buserelin addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 1413 nM (pChEMBL 5.849999904632568)
Descriptors: MW 469.01, ALogP 5.15, HBA 3, HBD 1, PSA 66.48, QED 0.56
Compound (SMILES): CC1(C)C[C@@H](C(N)=O)N(Cc2ccc(OCc3cccc(F)c3)cc2)C1
InChIKey: HFVPWDUISWUPNM-IBGZPJMESA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B expressed in Sf9 cells using benzylamine as substrate preincubated for 15 mins followed by substrate addition for 60 mins by Luminex assay
Measurement: IC50 = 1424 nM (pChEMBL 5.849999904632568)
Descriptors: MW 356.44, ALogP 3.49, HBA 3, HBD 1, PSA 55.56, QED 0.86
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1NC1CCN(Cc2ccc(OC)c(OC)c2)CC1
InChIKey: XYAGCTLZTXSMKI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant JAK2 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hr followed by anti-pSTAT1 antibody addition and measured after 30 mins by Lanthascreen TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 423.52, ALogP 3.02, HBA 6, HBD 3, PSA 91.51, QED 0.54
Compound (SMILES): CC(C)Nc1nc2ccccn2c1-c1ccc(O)cc1
InChIKey: KPRMDZKEUJUSHL-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 47 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96K76
Assay: Inhibition of USP47 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 267.33, ALogP 3.53, HBA 4, HBD 2, PSA 49.56, QED 0.76
Compound (SMILES): Cc1ccc(-c2c(-c3ccc(C#N)c(F)c3)nc(N3CCC(N)CC3)c(=O)n2C)cc1
InChIKey: BZQUYIKUKRZLHE-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of LSD1 (unknown origin) using H3K4me1 substrate by TR-FRET assay
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 417.49, ALogP 3.36, HBA 6, HBD 1, PSA 87.94, QED 0.71
Compound (SMILES): Cc1cc2ccnc(N[C@@H]3CCNC[C@H]3C(=O)NC3CCCCC3)c2[nH]c1=O
InChIKey: IKBQHNYWAGFECR-IAGOWNOFSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from His6-tagged BRD4 BD2 (1 to 477 residues)/BD1 Y97A mutant (unknown origin) after 30 mins by TR-FRET assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 383.5, ALogP 2.07, HBA 5, HBD 4, PSA 98.91, QED 0.65
Compound (SMILES): Cc1ccccc1N1CCN(C(=O)N2CCNc3cc(Cl)ccc32)CC1
InChIKey: BAIVKPDXBUZUCJ-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Antagonist activity at human V1a receptor expressed in human 1321N1 cells assessed as decrease in Arg8-vasopressin-stimulated calcium flux by fluorometric calcium assay
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 370.88, ALogP 3.82, HBA 3, HBD 1, PSA 38.82, QED 0.83
Compound (SMILES): Cc1c(Br)cnc2nc(N3CCN(C)CC3)c3nncn3c12
InChIKey: MWPVFFBPURHQLC-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]-N-alpha-methylhistamine from recombinant human histamine H3 receptor expressed in CHO-K1 cell membranes measured after 30 mins by microbeta scintillation counting method
Measurement: IC50 = 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 362.24, ALogP 1.5, HBA 7, HBD 0, PSA 62.45, QED 0.65
Compound (SMILES): COc1ccc(C2CC(=O)NCCS2)cc1
InChIKey: GVYWKFZAQBPVIC-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q02750
Assay: Binding affinity to full length biotinylated 6His/Avi-tagged/Tev-fused human MEK1 expressed in Escherichia coli in absence of AMP-PNP by SPR assay
Measurement: Kd = 430000 nM (pChEMBL 3.369999885559082)
Descriptors: MW 237.32, ALogP 1.99, HBA 3, HBD 1, PSA 38.33, QED 0.85
Compound (SMILES): CCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)O)C(C)C)[C@@H](C)CC
InChIKey: HFUSBRWOPZDLSP-DXNXPDASSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in HEK293 cells co-expressing Galpha(i1)-RlucII(91) assessed as induction of dissociation of Galpha(i1) from G-beta-gamma subunits incubated for 5 mins by BRET assay
Measurement: EC50 = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 1162.4
Compound (SMILES): COc1cc2c(cc1O)CCC(C)(CCNCCOCCOCCNc1c3c(nc4cc(Cl)ccc14)CCCC3)O2
InChIKey: YZABYNHVFXOCEC-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of recombinant human BChE using butyrylthiocholine iodide as substrate preincubated for 15 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 584.16, ALogP 5.69, HBA 8, HBD 3, PSA 94.1, QED 0.21
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H]1C/C=C\C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1)C(=O)O
InChIKey: OIEVKRWAKSOSSP-AZRMJBIHSA-N
Target: Neurotensin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95665
Assay: Displacement of [125I]Tyr3-neurotensin from human recombinant NTS2 stably expressed in human 1321N1 cell membranes incubated for 60 mins by gamma counter analysis
Measurement: Ki = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 716.88, ALogP -0.58, HBA 10, HBD 10, PSA 281.09, QED 0.07
Compound (SMILES): Cc1ccc(NC(=O)c2ncn(CC(=O)NCc3ccc4c(N)nccc4c3)n2)cc1C
InChIKey: DTGNUGZZTITRDZ-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NVM4
Assay: Inhibition of recombinant human PRMT7 using GST-GAR as substrate by hotspot assay
Measurement: IC50 = 69400 nM (pChEMBL 4.159999847412109)
Descriptors: MW 429.48, ALogP 2.59, HBA 7, HBD 3, PSA 127.82, QED 0.43
Compound (SMILES): Cc1cc(Nc2cc(N3CCN(C)CC3)ncn2)c(=O)n2c1C(=O)NC21CCCCC1
InChIKey: MOQHPHSZEODHGL-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BUB5
Assay: Inhibition of recombinant human N-terminal DYKDDDDK-tagged MNK1(1 to 424 residues) expressed in baculovirus expression system using TATKSGSTTKNR as substrate preincubated for 10 mins followed by ATP addition and measured after 40 mins by luminescence based assay
Measurement: IC50 = 51.2 nM (pChEMBL 7.289999961853027)
Descriptors: MW 423.52, ALogP 1.8, HBA 8, HBD 2, PSA 95.39, QED 0.78
Compound (SMILES): Nc1ncc(-c2nc(N3CCOCC3)c3ncn(CCCCCCC(=O)NO)c3n2)cn1
InChIKey: SHWBIBURMMWDKZ-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 in human HeLa nuclear extract using Boc-Lys(Ac)-AMC as substrate measured after 2 hrs by fluorescence based assay
Measurement: IC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 441.5, ALogP 1.16, HBA 11, HBD 3, PSA 157.2, QED 0.25
Compound (SMILES): c1cnc2c(Nc3ccc4c(-n5cccn5)nccc4c3)n[nH]c2c1
InChIKey: XCIOVXDWUWYQHU-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 327.35, ALogP 3.44, HBA 6, HBD 2, PSA 84.31, QED 0.53
Compound (SMILES): Nc1n[nH]c2cc(-c3ccc(=O)n(Cc4cccc(F)c4)c3)ccc12
InChIKey: FNHGPHDXAKOIJJ-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: Inhibition of recombinant human full-length N-terminal GST-fused MNK2 (1 to 465 residues) expressed in baculovirus expression system using GRSRSRSRSR as substrate measured after 2 hrs by ADP-glo luminescence assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 334.35, ALogP 3.16, HBA 4, HBD 2, PSA 76.7, QED 0.6
Compound (SMILES): CCCCNNC(=O)c1ccc(CNC(=O)c2ccccc2)cc1
InChIKey: PCJOVMYAXWJZSI-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Allosteric inhibition of HDAC3 in HEK293 cell lysates pre-incubated for 2 hrs before acetylated lysine-aminomethyl coumarin-BOC addition and measured after 2 hrs by fluorescence based assay
Measurement: IC50 = 260.6 nM (pChEMBL 6.579999923706055)
Descriptors: MW 325.41, ALogP 2.65, HBA 3, HBD 3, PSA 70.23, QED 0.52
Compound (SMILES): COC(=O)[C@@H]1C=C(O)C(=O)[C@H]2[C@@]1(C)CC[C@H]1C(=O)O[C@H](c3ccoc3)C[C@]21C
InChIKey: SBBHGDLVRCVJOA-GHTUPSMJSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opiod receptor expressed in CHO-K1 cells assessed as increase in forskolin induced cAMP production measured after 30 mins by HitHunter luminescence based assay
Measurement: EC50 = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 388.42, ALogP 3.12, HBA 7, HBD 1, PSA 103.04, QED 0.78
Compound (SMILES): Cc1cc(Nc2cc(Nc3ccccc3S(=O)(=O)C(C)C)c3cc[nH]c3n2)c(OC(C)C)cc1C1CCN(C)CC1
InChIKey: VQGSYFRVZZKBOB-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of Tel fused InsR (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 2 to 3 days by Bright-Glo luciferase assay
Measurement: IC50 = 5682 nM (pChEMBL 5.25)
Descriptors: MW 575.78, ALogP 7.14, HBA 7, HBD 3, PSA 99.35, QED 0.2
Compound (SMILES): O=C(O)c1ccc(-c2coc3ncc(-c4ccccc4)cc23)cc1Cl
InChIKey: KHPDNSBTNDXSBL-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RR4
Assay: Affinity Biochemical interaction (Enzymatic activity assay) EUB0000168b CAMKK2
Measurement: IC50 > 27000 nM (pChEMBL 4.568999767303467)
Descriptors: MW 349.77, ALogP 5.51, HBA 3, HBD 1, PSA 63.33, QED 0.53
Compound (SMILES): Cc1ccc2c(c1)CCCN2CC(=O)N1CCCCC1
InChIKey: MNZBOJZTNHRAKJ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]-NMS from muscarinic M3 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 66069.34 nM (pChEMBL 4.179999828338623)
Descriptors: MW 272.39, ALogP 2.76, HBA 2, HBD 0, PSA 23.55, QED 0.83
Compound (SMILES): Cc1cc(Cl)cc(N2C=Nc3cc(C)c(-c4cccc(O)c4)cc3C2C(=O)N(C)C[C@@H]2CCCN2)c1
InChIKey: SBUVEICNNWOGMB-XYXHBKGXSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Agonist activity at human SST2 expressed in CHO-K1 cells assessed as reduction in NKH477-induced intracellular cAMP accumulation
Measurement: EC50 = 0.33 nM (pChEMBL 9.479999542236328)
Descriptors: MW 503.05, ALogP 5.76, HBA 5, HBD 2, PSA 68.17, QED 0.47
Compound (SMILES): O=C(NO)c1ccc(CN2CCC3(CC2)CN(Cc2ccccc2)c2ccccc23)cc1
InChIKey: KUWUJLOSVWMVNA-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length N-terminal GST-tagged human HDAC6 expressed in baculovirus expression system using ZMAL as substrate incubated for 90 mins by fluorescence assay
Measurement: IC50 = 561 nM (pChEMBL 6.25)
Descriptors: MW 427.55, ALogP 4.36, HBA 4, HBD 2, PSA 55.81, QED 0.47
Compound (SMILES): CNC(=O)[C@@H]1CCCN1S(=O)(=O)c1ccc(Cl)c(COc2cccc3c(-n4ccnc4)cc(C(F)(F)F)nc23)c1Cl
InChIKey: YPZVBDHGFDAMKP-SFHVURJKSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at pSG5GAL4-DBD/LBD fused human RORgamma receptor expressed in COS7 cells co-expressing 5 copies of GAL4 response element after 18 hrs by luciferase reporter gene based assay
Measurement: EC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 628.46, ALogP 5.22, HBA 7, HBD 1, PSA 106.42, QED 0.3
Compound (SMILES): CCCCOC(=O)CC1c2cccc(Cl)c2S(=O)(=O)N1C(=O)c1ccc(C(F)(F)F)cc1
InChIKey: XUJLDFJCGXBHCG-UHFFFAOYSA-N
Target: Nucleotide-binding oligomerization domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC29
Assay: Antagonist activity at human NOD2 in HEK-Blue hNOD2 cells assessed as secreted alkaline phosphatase reporter activity preincubated for 3 hrs followed by stimulated with MDP for 20 hrs by Spectrophotometer method
Measurement: IC50 = 1390 nM (pChEMBL 5.860000133514404)
Descriptors: MW 489.9, ALogP 4.98, HBA 5, HBD 0, PSA 80.75, QED 0.42
Compound (SMILES): C[C@H](NC(=O)Cn1nc2ncccn2c1=O)c1ccc(Cl)c(F)c1
InChIKey: OVFQFWGUNDVOAQ-VIFPVBQESA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P0C0W8
Assay: Agonist activity at rat GPR139 expressed in CHO-K1 cells assessed as increase in calcium flux by calcium 5 dye based FLIPR assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 349.75, ALogP 1.56, HBA 6, HBD 1, PSA 81.29, QED 0.77
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3COCC4)c(Cl)cn2)C1
InChIKey: CUVDIVXPUWFCOD-UONOGXRCSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 in human MCF7 cells assessed as reduction in RNA Polymerase 2 CTD phosphorylation at Ser2 residues measured after 6 hrs by immunofluorescence assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 417.9, ALogP 2.76, HBA 6, HBD 2, PSA 98.14, QED 0.8
Compound (SMILES): O=C(Nc1ccc(-n2nccn2)nc1)N1CC[C@@H]2CN(Cc3cccc(Oc4ccc(Cl)cc4)c3)C[C@@H]21
InChIKey: YTZWSZKPPCLCFI-NLFFAJNJSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Inhibition of rat FAAH1 incubated for 60 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 516.01, ALogP 4.85, HBA 7, HBD 1, PSA 88.41, QED 0.39
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@@H]2CC3CCCCC3N2C1=O
InChIKey: NHBSWHPBPMPVCZ-NQUATQFZSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Antagonist activity at human MC3R expressed in HEK293 cells expressing the GScAMP22F cAMP reporter assessed as reduction in alpha-MSH-induced cAMP accumulation by cAMP split-luciferase reporter gene assay
Measurement: IC50 = 374 nM (pChEMBL 6.429999828338623)
Descriptors: MW 1088.32
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)O)c1nnc(C)n1-2
InChIKey: LJOSBOOJFIRCSO-AWEZNQCLSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of N-terminal his-tagged human recombinant BRD4 BD2 (44 to 460 residues) expressed in Escherichia coli using biotinylated H4K5acK8acK12acK16ac peptide as substrate pretreated for 30 mins followed by substrate addition and measured after 30 mins by Alphascreen analysis
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 400.89, ALogP 4.27, HBA 6, HBD 1, PSA 80.37, QED 0.71
Compound (SMILES): CCCCCCCC(=O)NS(=O)(=O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: VOJULRAUYRJNQO-XKLVTHTNSA-N
Target: Long-chain-fatty-acid--AMP ligase FadD28 (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WQ59
Assay: Inhibition of Mycobacterium tuberculosis H37Rv FAAL28 Spectra expressed in Escherichia coli BL21(DE3) cells assessed as cleavage of MEsG by spectroscopic analysis
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 472.52, ALogP -0.23, HBA 12, HBD 4, PSA 191.78, QED 0.32
Compound (SMILES): CC1(C)Oc2cc(C34CC5CC(CC(CN=[N+]=[N-])(C5)O3)C4)cc(O)c2[C@@H]2C[C@H](CO)CC[C@H]21
InChIKey: CULSUFZRKNZQEZ-CBPWPPFMSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Mus musculus
UniProt: P47936
Assay: Displacement of [3H]CP55940 from mouse CB2 receptor expressed in HEK293 cell membrane by scintillation counting method
Measurement: Ki = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 453.58, ALogP 5.54, HBA 5, HBD 2, PSA 107.68, QED 0.35
Compound (SMILES): CCC(=O)N(CCN1CCC(CCCc2ccccc2)CC1)c1ccc(OC)cc1
InChIKey: QOPUFSOTWZTLAJ-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-diprenorphin from human mu opioid receptor expressed in CHO cell membrane incubated for 150 mins by liquid scintillation counting method
Measurement: Ki = 74 nM (pChEMBL 7.130000114440918)
Descriptors: MW 408.59, ALogP 5.17, HBA 3, HBD 0, PSA 32.78, QED 0.54
Compound (SMILES): CCCCOC(=O)CC1c2cccc(C(=O)OCCCC)c2S(=O)(=O)N1C(=O)c1ccc(C(F)(F)F)cc1
InChIKey: LEJCUFNJDQUGLM-UHFFFAOYSA-N
Target: Nucleotide-binding oligomerization domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC29
Assay: Antagonist activity at human NOD2 in HEK-Blue hNOD2 cells assessed as secreted alkaline phosphatase reporter activity preincubated for 3 hrs followed by stimulated with MDP for 20 hrs by Spectrophotometer method
Measurement: IC50 = 4290 nM (pChEMBL 5.369999885559082)
Descriptors: MW 555.57, ALogP 5.28, HBA 7, HBD 0, PSA 107.05, QED 0.29
Compound (SMILES): O=C(Oc1ccc(CCO[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)cc1)c1ccccc1
InChIKey: XXIDDXLVNGGLSG-GQUPQBGVSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Competitive inhibition of human recombinant MAO-B expressed in baculovirus infected BTI cells assessed as inhibition of 4-hydroxyquinoline formation using varying concentration of kynuramine as substrate preincubated with enzyme for 10 mins followed by addition of substrate and measured after 15 mins by Lineweaver-Burk plot analysis
Measurement: Ki = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 404.42, ALogP 0.26, HBA 8, HBD 4, PSA 125.68, QED 0.38
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(C#CC#Cc2ccc(-c3cnc([C@@H]4CCCN4C(=O)[C@H](NC(=O)OC)c4ccccc4)[nH]3)cc2)[nH]1)C(C)C.Cl.Cl
InChIKey: IRVPRWISVYUDRG-GVYXSLNHSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 3a NS5A infected in Huh7 cells assessed as reduction in viral replication incubated 3 days and measured by bright Glo-luciferase reporter gene assay
Measurement: IC50 = 0.629 nM (pChEMBL 9.199999809265137)
Descriptors: MW 744.85, ALogP 5.01, HBA 8, HBD 4, PSA 174.64, QED 0.17
Compound (SMILES): CO[C@H](C)c1c(NC(=O)Nc2cnc(-n3nccn3)c(Cl)c2)cnc2cc(Cl)nn12
InChIKey: GBIASRXDYFFUED-SECBINFHSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Inhibition of MALT1 in human whole blood assessed as reduction in PMA//anti-CD28 antibody-induced IL2 level pre-incubated for 1 hrs before stimulation with PMA//anti-CD28 antibody by MSD assay
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 448.27, ALogP 3.36, HBA 9, HBD 2, PSA 124.15, QED 0.48
Compound (SMILES): c1cnc2[nH]cc(-c3ccc4ncc(NCc5ccoc5)cc4c3)c2c1
InChIKey: VCMYYTXPJIFJEA-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of N-terminal GST tagged human DYRK1B expressed in Sf21 cells incubated for 60 mins by ADP-Glo assay
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 340.39, ALogP 4.98, HBA 4, HBD 2, PSA 66.74, QED 0.48
Compound (SMILES): O=C(/N=C1\C=CC=C(C(=O)/N=C2\C=CC=C(C(=O)/N=C3\CC=C(S(=O)(=O)O)c4cc(S(=O)(=O)O)cc(S(=O)(=O)O)c43)C2)C1)/N=C1\C=CC=C(C(=O)/N=C2\C=CCC(C(=O)/N=C3\CC=C(S(=O)(=O)O)c4cc(S(=O)(=O)O)cc(S(=O)(=O)O)c43)=C2)C1
InChIKey: KWKVPRFHUNTXGS-HSNBEZQTSA-N
Target: Ectonucleoside triphosphate diphosphohydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5L3
Assay: Inhibition of human NTPDase2 expressed in green monkey Cos-7 cells using ATP as substrate preincubated for 3 mins followed by substrate addition by malachite green reagent based assay
Measurement: IC50 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 1269.25
Compound (SMILES): Cc1cc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)ccc1NC(=O)/C=C/CN(C)C
InChIKey: UQDLBEGORWSOQS-VHTFYLNKSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of CDK2/cyclin A2 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 458.57, ALogP 3.32, HBA 6, HBD 2, PSA 90.46, QED 0.53
Compound (SMILES): Cc1nc(N)nc(N[C@@H](C)c2cc3ccc(F)cn3c(=O)c2-c2ccccc2)c1C#N
InChIKey: YYNGBTBSCVESON-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human Raji cells assessed as reduction in phosphorylation of AKT at 473 measured after 2 hr by alpha screen assay
Measurement: IC50 = 0.89 nM (pChEMBL 9.050000190734863)
Descriptors: MW 414.44, ALogP 3.83, HBA 7, HBD 2, PSA 109.1, QED 0.53
Compound (SMILES): C[C@@H](c1ccc2ncccc2c1)c1nnc2sc(Nc3cnn(C)c3)nn12
InChIKey: ONRZEVZCRXEKBO-NSHDSACASA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-MET in human SNU-5 cells measured after 6 hrs by steady-glo luciferase reporter gene assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 376.45, ALogP 3.36, HBA 9, HBD 1, PSA 85.82, QED 0.52
Compound (SMILES): COc1c(C)c2c(c(O)c1CCOCC(=O)Nc1ccc(Cl)cc1)C(=O)OC2
InChIKey: SPUZODJMFSRENB-UHFFFAOYSA-N
Target: Inosine-5'-monophosphate dehydrogenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P12268
Assay: Inhibition of human IMPDH2 expressed in Escherichia coli assessed as apparent inhibition constant using NAD as substrate by fluorescence assay
Measurement: Ki = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 405.83, ALogP 3.23, HBA 6, HBD 2, PSA 94.09, QED 0.54
Compound (SMILES): O=C(c1ccccc1)N(CCCN1CCN(c2ccccn2)CC1)CC1CC1
InChIKey: SHULDTNTBVWTML-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at human 5HT2A receptor expressed in CHO-K1 cells measured after 15 mins by FLIPR assay
Measurement: IC50 = 7719 nM (pChEMBL 5.110000133514404)
Descriptors: MW 378.52, ALogP 3.15, HBA 4, HBD 0, PSA 39.68, QED 0.71
Compound (SMILES): COc1ccccc1N1CCN(CCCCC(=O)Nc2cccc(C(C)C)c2)CC1.Cl
InChIKey: SMOYHSVPDPATSS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from human 5HT1A receptor expressed in HEK293 cells measured after 1 hr by microbeta counting method
Measurement: Ki = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 409.57, ALogP 4.75, HBA 4, HBD 1, PSA 44.81, QED 0.61
Compound (SMILES): NS(=O)(=O)c1cccc(-c2nnc(-c3cccc([N+](=O)[O-])c3)o2)c1
InChIKey: FQQAMDWTHCXCRZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 by stopped flow CO2 hydrase assay
Measurement: Ki = 52.4 nM (pChEMBL 7.28000020980835)
Descriptors: MW 346.32, ALogP 1.96, HBA 7, HBD 1, PSA 142.22, QED 0.56
Compound (SMILES): Cc1ccsc1C(=CCCN(C)C(CO)C(=O)NCc1ccc(Cl)cc1)c1sccc1C
InChIKey: HABCOXFZLVZQIL-UHFFFAOYSA-N
Target: GABA transporter 3 (SINGLE PROTEIN), Mus musculus
UniProt: P31649
Assay: Inhibition of mouse GAT2 expressed in HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 35 mins by liquid scintillation method
Measurement: IC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 489.11, ALogP 5.51, HBA 5, HBD 2, PSA 52.57, QED 0.4
Compound (SMILES): Cc1ccsc1C(=CCCN(C)C(CO)C(=O)NCc1ccc(F)cc1)c1sccc1C
InChIKey: JLHYAWPUHDPARD-UHFFFAOYSA-N
Target: GABA transporter 3 (SINGLE PROTEIN), Mus musculus
UniProt: P31649
Assay: Inhibition of mouse GAT2 expressed in HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 35 mins by liquid scintillation method
Measurement: IC50 = 22387.21 nM (pChEMBL 4.650000095367432)
Descriptors: MW 472.65, ALogP 5, HBA 5, HBD 2, PSA 52.57, QED 0.44
Compound (SMILES): C[C@H](C(=O)Nc1cc(C2CC2)[nH]n1)c1ccc(C2=CCN(C(=O)/C=C/CN(C)C)CC2)cc1
InChIKey: IEVJHGZSBPGTMO-WRFKIARRSA-N
Target: Cyclin-dependent kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12 (unknown origin) using ULight - 4E - BP1( Thr37 / Thr46 ) as substrate preincubated for 60 mins bu LANCE-TR-FRET assay
Measurement: IC50 = 235 nM (pChEMBL 6.630000114440918)
Descriptors: MW 447.58, ALogP 3.76, HBA 4, HBD 2, PSA 81.33, QED 0.6
Compound (SMILES): Cn1cc(-c2cc(-c3cnn(C4(CC#N)CN(CC(F)(F)F)C4)c3)n3ccnc3c2)cn1
InChIKey: CKAYRDAFVZIXKY-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: JAK Caliper Enzyme Assay at 1mM ATP: Compounds were added to a 384-well plate. Reaction mixtures contained 10 mM HEPES, pH 7.4, 10 mM MgCl2, 0.01% BSA, 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAM-KKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20% to 30% phosphorylation. The assays were stopped with 15 μL of 180 mM HEPES, pH 7.4, 20 mM EDTA, and 0.2% Coating Reagent 3. The assay plates were placed on a Caliper Life Science LC3000 instrument, and each well was sampled using appropriate separation conditions to measure the unphosphorylated and phosphorylated peptide.
Measurement: IC50 = 252 nM (pChEMBL 6.599999904632568)
Descriptors: MW 440.43, ALogP 3.09, HBA 8, HBD 0, PSA 79.97, QED 0.48
Compound (SMILES): CCCCN[C@@H](Cc1c[nH]c2ccccc12)C(=O)NCCC1CCN(Cc2ccccc2)CC1
InChIKey: HXSAUIIDIMVOET-NDEPHWFRSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE using acetylthiocholine iodide as substrate measured for 5 mins by Ellman's method
Measurement: IC50 = 25400 nM (pChEMBL 4.590000152587891)
Descriptors: MW 460.67, ALogP 4.89, HBA 3, HBD 3, PSA 60.16, QED 0.34
Compound (SMILES): CC(C)[C@H]1N(C(=O)OC(C)(C)C)CC[C@]12C(=O)N(c1cccc(-c3ccc(CO)c(S(C)(=O)=O)c3)c1)c1ccccc12
InChIKey: ZWVQGRNZPMCKOJ-CYTLCNBWSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Inverse agonist activity at human LXRbeta transfected in human HEK293T cells co-transfected with pSG5 and pGL3/(DR-4)-c-fos-FF-luc/pCMV/Renilla-luc assessed as receptor transactivation incubated for 20 hrs by dual luciferase reporter gene assay
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 590.74, ALogP 5.83, HBA 6, HBD 1, PSA 104.22, QED 0.4
Compound (SMILES): COc1cc(NC(=O)/C=C/CN2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Nc2ccccc2S(=O)(=O)C(C)C)n1
InChIKey: JFJBQYDTDVUFOI-JXMROGBWSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met (unknown origin) using peptide substrate incubated for 60 mins in presence of ATP by HTRF assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 614.17, ALogP 4.55, HBA 10, HBD 3, PSA 128.79, QED 0.26
Compound (SMILES): CC1(C(=O)N2CCC[C@@H](c3nc(-c4ccc(C(=O)Nc5cc(C(F)(F)F)ccn5)c(F)c4F)c4c(N)nccn34)C2)COC1
InChIKey: JRFPFHCOXJBYPH-OAHLLOKOSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human PBMC assessed as reduction in cell surface CD69 expression preincubated for 1 hr followed by stimulation with goat anti-human IgM F(ab')2 for 18 hrs by immunostaining analysis
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 615.56, ALogP 4.67, HBA 8, HBD 2, PSA 127.74, QED 0.31
Compound (SMILES): O=S(=O)(c1ccc(F)cc1)C1(c2ccc(C(OCc3c(F)cccc3F)(C(F)(F)F)C(F)(F)F)cc2)CCCC1
InChIKey: VCGZXUITPFWUPQ-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Transactivation of PXR in human HepG2 cells
Measurement: EC50 = 463 nM (pChEMBL 6.329999923706055)
Descriptors: MW 596.51, ALogP 7.88, HBA 3, HBD 0, PSA 43.37, QED 0.21
Compound (SMILES): C[C@@H](Nc1c(Cl)cnc2ccc(-c3ccc(S(C)(=O)=O)nc3)cc12)c1ccccc1F
InChIKey: GLHKTYUJPHIPSK-CQSZACIVSA-N
Target: Tumor necrosis factor (SINGLE PROTEIN), Homo sapiens
UniProt: P01375
Assay: Inhibition of exogenous human TNFalpha in HEK-Blue-CD40L cells assessed as reduction in TNF-alpha-induced NFkappaB activation incubated for 18 hrs by quanti-blue based SEAP assay
Measurement: IC50 = 909 nM (pChEMBL 6.039999961853027)
Descriptors: MW 455.94, ALogP 5.67, HBA 5, HBD 1, PSA 71.95, QED 0.42
Compound (SMILES): Cc1ccc(Nc2cc(N3CCC[C@@H](N)C3)nc3ccnn23)c(C)c1
InChIKey: PPDZWZHBFPWDTL-OAHLLOKOSA-N
Target: Dipeptidyl peptidase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6V1X1
Assay: Inhibition of DPP8 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 336.44, ALogP 3.02, HBA 6, HBD 2, PSA 71.48, QED 0.77
Compound (SMILES): CCCCCCCC(=O)Nc1nc2[nH]c(CN3CCN(Cc4ccccc4)CC3)c(CN3CCN(Cc4ccccc4)CC3)c2c(=O)[nH]1
InChIKey: KRALMKXJKVKMSA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using using myelin basic protein as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting method
Measurement: IC50 = 7050 nM (pChEMBL 5.150000095367432)
Descriptors: MW 652.89, ALogP 5.19, HBA 7, HBD 3, PSA 103.6, QED 0.15
Compound (SMILES): CCN(C)C(=O)Oc1ccc(-c2cc(=O)c3c(OC(=O)N(C)CC)cc(OC(=O)N(C)CC)cc3o2)cc1
InChIKey: MBGXXUPMENAELF-UHFFFAOYSA-N
Target: Butyrylcholinesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9JKC1
Assay: Inhibition of rat serum BChE using acetylthiocholine iodide as substrate measured after 15 mins by Ellman's method
Measurement: IC50 = 16200 nM (pChEMBL 4.789999961853027)
Descriptors: MW 525.56, ALogP 4.81, HBA 8, HBD 0, PSA 118.83, QED 0.43
Compound (SMILES): Cc1cc2nn(CC(=O)N[C@@H](C)c3ccc(Cl)cc3)c(=O)n2c(C)n1
InChIKey: VAZKFZBDPBRQNY-NSHDSACASA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P0C0W8
Assay: Agonist activity at rat GPR139 expressed in CHO-K1 cells assessed as increase in calcium flux by calcium 5 dye based FLIPR assay
Measurement: EC50 >= 100 nM (pChEMBL 7)
Descriptors: MW 359.82, ALogP 2.04, HBA 6, HBD 1, PSA 81.29, QED 0.77
Compound (SMILES): Cc1cc(OC2CCC3(CCCC3)CC2)c(CN2CCC(C(=O)O)CC2)c2ccccc12
InChIKey: CFFHCGFANGCPRJ-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Binding affinity to recombinant human S1P5 receptor expressed in Chem-1 cell membrane by 33P-SIP binding assay
Measurement: Ki = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 435.61, ALogP 6.33, HBA 3, HBD 1, PSA 49.77, QED 0.6
Compound (SMILES): CC(C)CC(=O)Nc1cncc(-c2cc3c(-c4nc5c(-c6ccoc6)cccc5[nH]4)n[nH]c3cn2)c1
InChIKey: LDJDCWZCPATNIZ-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: TGF-beta 1 Assay: Compound Screening: Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:2, 11-point dose-response curves from 10 μM to 1.87 nM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well clear bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. LL29 cells were plated at 1,500 cells/well in 80 μl/well F12 medium supplemented with 1% Fetal Bovine Serum. One hour after addition of the cells, TGF-β1 (Peprotech; 20 ng/mL) was added to the plates to induce fibrosis (ref. 1 and 2 above). Wells treated with TGF-β1 and containing DMSO were used as controls. Cells were incubated at 37° C. and 5% CO2 for 4 days. Following incubation for 4 days, SYTOX green nucleic acid stain (Life Technologies [Thermo Fisher Scientific]) was added to the wells at a final concentration of 1 uM and incubated at room temperature for 30 min. Cells were then fixed using 4% formaldehyde (Electron Microscopy Sciences), washed 3 times with PBS followed by blocking and permeabilization using 3% Bovine Serum Albumin (BSA; Sigma) and 0.3% Triton X-100 (Sigma) in PBS. Cells were then stained with antibody specific to α-smooth muscle actin (aSMA; Abcam) (ref. 1 and 2 above) in 3% Bovine Serum Albumin (BSA; Sigma) and 0.3% Triton X-100 (Sigma) in PBS, and incubated overnight at 4° C. Cells were then washed 3 times with PBS, followed by incubation with Alexa Flor-647 conjugated secondary antibody (Life Technologies [Thermo Fisher Scientific]) and DAPI at room temperature for 1 hour. Cells were then washed 3 times with PBS and plates were sealed for imaging. αSMA staining was imaged by excitation at 630 nm and emission at 665 nm and quantified using the Compartmental Analysis program on the CellInsight CX5 (Thermo Scientific). Dead or apoptotic cells were excluded from analysis based on positive SYTOX green staining. % of total cells positive for αSMA were counted in each well and normalized to the average of 11 wells treated with TGF-β1 on the same plate using Dotmatics' Studies Software. The normalized averages (fold change over untreated) of 3 replicate wells for each compound concentration were used to create dose-responses curves and EC50 values were calculated using non-linear regression curve fit in the Dotmatics' Studies Software.
Measurement: EC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 477.53, ALogP 5.81, HBA 6, HBD 3, PSA 125.38, QED 0.28
Compound (SMILES): C=CC(=O)Nc1cccc(-c2c[nH]c3ncnc(Nc4ccc(OCc5ccccn5)c(Cl)c4)c23)c1
InChIKey: GOAJIFLFYKGQGD-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibiton of EGFR (unknown origin) expressed in human A431 cells assessed as reduction in EGFR induced cell viability after 96 hrs by CellTiter-Glo assay
Measurement: IC50 = 1675 nM (pChEMBL 5.78000020980835)
Descriptors: MW 496.96, ALogP 6.12, HBA 6, HBD 3, PSA 104.82, QED 0.22
Compound (SMILES): CCc1ccc(-c2n[nH]c(=O)o2)cc1
InChIKey: JUMIIGQRXSBEEX-UHFFFAOYSA-N
Target: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Biochemical Notum Enzymatic Activity Assay: An Echo liquid handler was used to acoustically dispense 500 nL of compounds into dry Greiner 384-well plates (catalog #781076), followed by 25 μL of 2 μM trisodium 8-octanoyloxypyrene-1,3,6-trisulfonate (OPTS, Sigma #74875) solution in 50 mM Tris, 5 mM CaCl2), 0.5 mM MgCl2, pH 7.4 assay buffer, and 25 μL of 2.38 nM notum carboxyesterase enzyme solution in the same buffer to every well in the assay plate. After 1 hour incubation at room temperature, fluorescence was measured on a PheraSTAR FSX microplate reader with an excitation wavelength of 485 nm and emission wavelength of 520 nm.
Measurement: IC50 = 152 nM (pChEMBL 6.820000171661377)
Descriptors: MW 190.2, ALogP 1.59, HBA 3, HBD 1, PSA 58.89, QED 0.78
Compound (SMILES): CNC(=O)c1c(NC(=S)Nc2ccccc2)sc2c1C(C)CCC2
InChIKey: ZDGOATQEDQKXLA-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Antagonist activity at CXCR4 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 359.52, ALogP 4.36, HBA 3, HBD 3, PSA 53.16, QED 0.71
Compound (SMILES): Cc1ccccc1C(C[N+](=O)[O-])c1c(-c2ccccc2)[nH]c2ccccc12
InChIKey: YETFDRBZGXBULL-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Positive allosteric modulatory activity at human CB1 receptor expressed in CHO-K1 cells assessed as increase in CP55940-induced inhibition of forskolin-stimulated cAMP production preincubated for 30 mins followed by CP55940 addition and measured after 60 mins by Hit-hunter assay
Measurement: EC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 356.43, ALogP 5.55, HBA 2, HBD 1, PSA 58.93, QED 0.38
Compound (SMILES): O=S(=O)(c1ccc(F)cc1)N(CCCN1CCC(c2noc3cc(F)ccc23)CC1)C1COC1
InChIKey: SHZVXUBQYBBGNZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Antagonist activity at human 5HT2A receptor expressed in CHO-K1 cells measured after 15 mins by FLIPR assay
Measurement: IC50 = 15.1 nM (pChEMBL 7.820000171661377)
Descriptors: MW 491.56, ALogP 3.77, HBA 6, HBD 0, PSA 75.88, QED 0.48
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CCc5ccccc54)CC3)s2)cc1
InChIKey: LGIUHWQDGPFXSG-VWLOTQADSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human recombinant full length GPR40 overexpressed in human HEK293 cells assessed as increase in intracellular calcium level measured over 3 mins by calcium 4 dye based FLIPR assay
Measurement: EC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 499.68, ALogP 6.39, HBA 4, HBD 1, PSA 49.77, QED 0.37
Compound (SMILES): Cc1cn2c(n1)c(C#N)c(C)c1cnc(N)nc12
InChIKey: GLDQROMTPTWBPL-UHFFFAOYSA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of human full-length N-terminal GST tagged CDK6 (1 to 326 residues)/GST-tagged cyclinD3 (1 to 292 residues) expressed in baculovirus expression system using ULight-elF4E-binding protein 1 peptide as substrate measured after 30 mins by LANCE assay
Measurement: IC50 = 3090 nM (pChEMBL 5.510000228881836)
Descriptors: MW 238.25, ALogP 1.35, HBA 6, HBD 1, PSA 92.89, QED 0.64
Compound (SMILES): Cc1ncsc1-c1ccc([C@H](C)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCCCCCNCCCCONC(=O)c2ccc(F)c(F)c2Nc2ccc(I)cc2F)C(C)(C)C)cc1
InChIKey: DYLGPTDXXUWFMK-ARFQKLFXSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P36507
Assay: Binding affinity to MEK2 (unknown origin) incubated for 1 hr by qPCR based KINOMEscan assay
Measurement: Kd = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 1104.13
Compound (SMILES): Cc1[nH]c(/C=C2\C(=O)Nc3ccc(C(=O)N[C@H](C)c4ccccc4)cc32)c(C)c1NC(=O)C(O)CCl
InChIKey: HEIMVEZLCRDTPW-SMOHNXANSA-N
Target: Beta-adrenergic receptor kinase 1 (SINGLE PROTEIN), Bos taurus
UniProt: P21146
Assay: Inhibition of bovine GRK2 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 506.99, ALogP 4.15, HBA 4, HBD 5, PSA 123.32, QED 0.24
Compound (SMILES): CC1(C)CNc2nc(nc(-c3cccc(C(F)(F)F)n3)n2)Nc2cc(cc(C(F)(F)F)c2)CCCCO1
InChIKey: HFAJWEDAJNVOPX-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R172K mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-ketoglutarate and NADPH as substrate preincubated with enzyme for 15 mins followed by substrate addition by fluorescence based assay
Measurement: IC50 = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 526.49, ALogP 6.26, HBA 7, HBD 2, PSA 84.85, QED 0.36
Compound (SMILES): CCn1nc(C)cc1C(=O)/N=c1\n(C)c2ccccc2n1C/C=C/Cn1/c(=N/C(=O)c2cc(C)nn2CC)n(C)c2cccc(CN3CCOCC3)c21
InChIKey: BGILSESIPXJNAD-DSERURCISA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Agonist activity at STING in human PBMC cells assessed as increase in IFNp by electrochemiluminescence assay
Measurement: EC50 < 1 nM (pChEMBL 9)
Descriptors: MW 717.88, ALogP 3.89, HBA 12, HBD 0, PSA 126.69, QED 0.2
Compound (SMILES): CCCC(C)COc1ccc([C@@H](NC(=O)[C@@H](C)c2ccccc2)c2nnco2)cc1
InChIKey: YQUKTXRBHFAWOY-RXJZEZJSSA-N
Target: G protein-coupled receptor 88 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZN0
Assay: Agonist activity at GPR88 (unknown origin) expressed in CHO cells assessed as inhibition of forskolin-induced cAMP production by TR-FRET assay
Measurement: EC50 = 537 nM (pChEMBL 6.269999980926514)
Descriptors: MW 407.51, ALogP 4.89, HBA 5, HBD 1, PSA 77.25, QED 0.52
Compound (SMILES): N[C@H]1CCNC(=O)CC[C@@H](C(=O)NCc2ccccc2CC(=O)O)NC(=O)C[C@H](Cc2ccc(O)cc2)NC1=O
InChIKey: QXXQYOLAIXPCDN-PMVMPFDFSA-N
Target: Interleukin-1 receptor antagonist protein (SINGLE PROTEIN), Homo sapiens
UniProt: P18510
Assay: Binding affinity to recombinant full length human IRAP expressed in HEK293T cells using Leu-MCA as substrate
Measurement: Ki = 887 nM (pChEMBL 6.050000190734863)
Descriptors: MW 553.62, ALogP -0.13, HBA 7, HBD 7, PSA 199.95, QED 0.25
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1C#Cc1nn(C2CCN(C)CC2)c2ncnc(N)c12
InChIKey: LQSGDXCDNZWTJN-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Kinase Inhibition Assays: The aim of this experiment is to detect the inhibitory activity of the compounds of the present invention against in vitro protein kinases using isotope labeling (labeled gamma phosphate groups on ATP). Kinase inhibition profiles were determined using KinaseProfiler services provided by Euro fins, and ATP concentrations used are the Km of corresponding kinases. In this study, we examined Abl (T315I) (h), ALK (h), ARK5 (h), Axl (h), Blk (h), Bmx (h), BTK (h), B-Raf (H), ckit (h), cSRC (h), CDK7, CHK1 (h), c-RAF (h), DDR2 (h), EGFR (h), EphA1 (h), EphA2 (h), EphA8 (h (H), FGF (h), Ft (h), Ft (h), F (h), F (h), Ft (h), Hb (h), ErbB2 (h), FAK (h) (H), JK3 (h), IKKalpha (h), IKKbeta (h), Itk (h), JAK3 (h), JNK11 (h), KDR (h), Lyn (h), MAPK1 (h), MEK1 (h (H), PKA (h), PKB [alpha](h), PKB [beta] (h), PKC [alpha] (h), Ret (H), RIPK2 (h), Src (1-530) (h), TAK1 (h), TBK1 (h), Tec (h) activated, Tie2 (h), TrkA (h), ULK3 (h) Yes (h), PI3 Kinase a (h) and other kinase in vitro inhibitory activity. The kinase inhibitory activity of the test compound is expressed as IC50 (half inhibitory concentration) or the inhibitory rate of the test compound at a concentration of 10 ??M for kinase activity. IC50 values can be obtained by calculating the inhibition rate of the kinase activity by the test compound at a series of different concentrations. The assay was as follows: In a reaction tube, the buffer (8 mM MOPS, pH 7.0, 0.2 mM EDTA, 10 mM MnCl2), the kinase to be tested (5-10 mU), the substrate to be tested kinase, 10 mM acetic acid Magnesium and gamma 33P-ATP solutions, as well as different concentrations of the test compound. MgATP was then added to the reaction to initiate the enzymatic reaction and incubated at room temperature for 40 minutes. The reaction was finally quenched with 5 ul of 3% phosphate buffer and 10 uL of the reaction solution was titrated onto a filtermat A membrane, washed three times with 75 mM phosphate solution for 5 minutes each, and washed again with methanol. Finally, the filtermat A film is dried and scintigraphized, and the size of the scintillation count reflects the degree to which the substrate is phosphorylated, thereby demonstrating that the kinase activity is inhibited. Among them, the percentage of the remaining active protein=the active protein of the experimental group the active protein of the control group 100%.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 533.56, ALogP 4.65, HBA 7, HBD 2, PSA 101.96, QED 0.37
Compound (SMILES): O=C(Cn1c(=O)oc2ccccc21)N/N=C(\C=C\c1ccccc1)c1ccccc1
InChIKey: MUVRMWWPDCSDLD-DEWWSIIASA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate incubated for 30 mins by Amplex red reagent based fluorescence analysis
Measurement: Ki = 19000 nM (pChEMBL 4.71999979019165)
Descriptors: MW 397.43, ALogP 3.83, HBA 5, HBD 1, PSA 76.6, QED 0.4
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc2nccc(Oc3ccc(C(=O)Nc4ccccn4)cc3)c2c1
InChIKey: PEBORLYUHFFQJJ-FNORWQNLSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of human recombinant full length N-terminal His6-tagged BTK expressed in baculovirus infected Sf9 cells using fluorescein labeled Blk/Lyntide substrate preincubated with enzyme for 60 mins followed by further incubation with substrate and ATP for 120 mins by IMAP assay
Measurement: IC50 = 7.2 nM (pChEMBL 8.140000343322754)
Descriptors: MW 467.53, ALogP 4.73, HBA 6, HBD 2, PSA 96.45, QED 0.36
Compound (SMILES): COC(=O)N(C)c1c(N)nc(-n2nc(Cc3ccccc3F)c3cc(F)ccc32)nc1N
InChIKey: FSHGCJDDICOAML-UHFFFAOYSA-N
Target: Soluble guanylate cyclase alpha1/beta1 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q02153
Assay: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay
Measurement: EC50 = 960 nM (pChEMBL 6.019999980926514)
Descriptors: MW 439.43, ALogP 3.05, HBA 8, HBD 2, PSA 125.18, QED 0.5
Compound (SMILES): CCCn1nc(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)c(Cc2ccc(OC(C)C)cc2)c1C
InChIKey: IFJMLDQRJZAXGJ-VZWAGXQNSA-N
Target: Sodium/glucose cotransporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13866
Assay: Inhibition of human SGLT1 expressed in COS7 cells assessed as reduction in [14C]-AMG uptake
Measurement: IC50 = 10300 nM (pChEMBL 4.989999771118164)
Descriptors: MW 450.53, ALogP 1.16, HBA 9, HBD 4, PSA 126.43, QED 0.45
Compound (SMILES): CC(C)OC(=O)c1c(NC(=S)Nc2ccccc2)sc2c1C(C)CCC2
InChIKey: KULWOOOACKNVEX-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Antagonist activity at CXCR4 (unknown origin) expressed in U2OS cells cotransfected with beta-arrestin/TEV protease fusion protein and beta-lactamase assessed as inhibition of CXCL8-induced beta arrestin2 recruitment preincubated for 30 mins followed by CXCL8 stimulation and measured after 5 hrs by FRET based fluorescence/Tango assay
Measurement: IC50 = 9300 nM (pChEMBL 5.03000020980835)
Descriptors: MW 388.56, ALogP 5.56, HBA 4, HBD 2, PSA 50.36, QED 0.53
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)[C@@H](C)Cc1c(C)cc(O)cc1C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)O
InChIKey: KIXBLNINVHGOFN-NJFSYGJFSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69,593 from human KOR expressed in mouse HN9.10 cell membranes incubated for 2 hrs by liquid scintillation counting based radioligand competition assay
Measurement: IC50 = 416.87 nM (pChEMBL 6.380000114440918)
Descriptors: MW 1233.53
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)nc1
InChIKey: HJNYNZZNOGDODX-CLOLKSBNSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin)
Measurement: IC50 = 402 nM (pChEMBL 6.400000095367432)
Descriptors: MW 559.07, ALogP 4.45, HBA 7, HBD 3, PSA 119.14, QED 0.27
Compound (SMILES): C[C@H](NC(=O)Cn1nc2cccc(N3CCCCC3)n2c1=O)c1ccc(OC(F)(F)F)cc1
InChIKey: VZNYDHALWZBZRW-HNNXBMFYSA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P0C0W8
Assay: Agonist activity at rat GPR139 expressed in CHO-K1 cells assessed as increase in calcium flux by calcium 5 dye based FLIPR assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 463.46, ALogP 3.26, HBA 7, HBD 1, PSA 80.87, QED 0.61