lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H](C(=O)Nc1ccc(F)cc1)C12CC(NC(=O)c3ccc(F)c(Cl)c3)(C1)C2
InChIKey: QRTDJSSUMTUYJH-BQXHSLBWSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human whole blood stimulated with IFNgamma/LPS using L-tryptophan/kynurenine as substrate incubated for 15 mins prior to IFNgamma/LPS stimulation and further incubated for 18 hrs followed by isotope labeled L-tryptophan/kynurenine addition on day 2 by LC/MS-MS analysis
Measurement: IC50 = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 404.84, ALogP 4.55, HBA 2, HBD 2, PSA 58.2, QED 0.77
Compound (SMILES): Cn1nccc1[C@H]1CCC[C@@H]1Oc1ccc(S(=O)(=O)Nc2ccncn2)c(F)c1F
InChIKey: WMJRYBDMGFCCAB-OCCSQVGLSA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human NaV1.5/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 = 84000 nM (pChEMBL 4.079999923706055)
Descriptors: MW 435.46, ALogP 3, HBA 7, HBD 1, PSA 99, QED 0.64
Compound (SMILES): COc1cc2c(cc1OC)CN(CCc1ccc(NC(=O)/C=C/c3ccc(Oc4ccc(-c5cccnc5)cc4)nc3)cc1)CC2
InChIKey: LSHYTROHYLREBD-VIZOYTHASA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Reversal of Pgp-mediated DOX resistance in human SW620/AD300 cells assessed as concentration required to show half of DOX IC50 incubated for 48 hrs by SRB assay
Measurement: EC50 = 103.4 nM (pChEMBL 6.989999771118164)
Descriptors: MW 612.73, ALogP 7.21, HBA 7, HBD 1, PSA 85.81, QED 0.16
Compound (SMILES): Cc1ccc(-c2ncnc(Nc3ccc4ncoc4c3)c2O)cc1
InChIKey: ZTMRGLGHRWHSBX-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of activated factor X (unknown origin) using CH3O-CO-D-CHG-Gly-Arg-pNA-AcOH as substrate by fluorescence based assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 318.34, ALogP 4.04, HBA 6, HBD 2, PSA 84.07, QED 0.59
Compound (SMILES): NS(=O)(=O)c1ccc(Oc2ccc(F)c(Cl)c2)c(CC2CNC2)c1
InChIKey: ZSGMIQCURGKNHT-UHFFFAOYSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Agonist activity at His6-tagged-human SOS1 catalytic domain (564 to 1049 residues) expressed in Escherichia coli BL21-CodonPlus-RIPL cells assessed as increase in SOS1-mediated GDP/GTP nucleotide exchange upon K-Ras G12D mutant (1 to 169 residues) by BODIPY-GDP assay
Measurement: EC50 = 4320 nM (pChEMBL 5.369999885559082)
Descriptors: MW 370.83, ALogP 2.68, HBA 4, HBD 2, PSA 81.42, QED 0.85
Compound (SMILES): Cc1ccc(NC(=O)c2cc3cccc(O)c3oc2=N)cc1
InChIKey: SKZQOFVKMNLPBF-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C4 (SINGLE PROTEIN), Homo sapiens
UniProt: P17516
Assay: Inhibition of recombinant AKR1C4 (unknown origin) assessed as reduction in S-tetralol-induced dehydrogenase activity by measuring NADPH level
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 294.31, ALogP 3.18, HBA 4, HBD 3, PSA 86.32, QED 0.68
Compound (SMILES): Cc1ccc2[nH]c(C(=O)N[C@H]3CN(S(=O)(=O)c4ccccc4)C[C@@H]3C(=O)N[C@@H]3CCCNC3)cc2c1
InChIKey: YCZKMQXSVCMJPL-IZIIKQMZSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay
Measurement: EC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 509.63, ALogP 1.76, HBA 5, HBD 4, PSA 123.4, QED 0.4
Compound (SMILES): CC(C)C[C@@H](NC1CCOCC1)C(=O)N1CCC[C@H]1C(=O)NCc1ccc2c(N)nccc2c1
InChIKey: AKVSSJSDJAAVMC-PKTZIBPZSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of thrombin (unknown origin)
Measurement: IC50 = 281 nM (pChEMBL 6.550000190734863)
Descriptors: MW 467.61, ALogP 2.61, HBA 6, HBD 3, PSA 109.58, QED 0.55
Compound (SMILES): CC(C)C[C@@H](NC1CCC(F)(F)CC1)C(=O)N1CCC[C@H]1C(=O)NCc1ccc2c(N)nccc2c1
InChIKey: PFQAPMQWNKBPIC-PKTZIBPZSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of thrombin (unknown origin)
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 501.62, ALogP 4.01, HBA 5, HBD 3, PSA 100.35, QED 0.51
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3C[C@H]4C[C@@H]3C[C@H]4CC#N)c12
InChIKey: KGKZRAAHCZTDQA-WYUUTHIRSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of N-terminal His-tagged human JAK2 catalytic domain incubated for 20 mins in presence of TK substrate-biotin by TR-FRET assay
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 282.35, ALogP 2.6, HBA 3, HBD 2, PSA 85.33, QED 0.89
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)CCN3CCOCC3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: OIBZQPIUCJMUGP-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]-NECA from human A2A receptor expressed in CHO cells
Measurement: Ki = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 459.51, ALogP 1.79, HBA 9, HBD 2, PSA 119.78, QED 0.45
Compound (SMILES): COc1ccc(CC(=O)Nc2ncc(-c3ccc(OCCCCN4CCCC4)cc3)s2)cc1OC
InChIKey: FTIIXIHLGZZUFN-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electric eel AChE using acetylcholine iodide as substrate by spectrophotometry based Ellman's method
Measurement: IC50 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 495.65, ALogP 5.26, HBA 7, HBD 1, PSA 72.92, QED 0.35
Compound (SMILES): C=CC(=O)Nc1cccc(Nc2nc(Nc3ccc4c(c3)B(O)OC4)ncc2C(F)(F)F)c1
InChIKey: IACRSHDPMMMKDK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in baculovirus expression system using Ulight-Poly GT as substrate incubated for 2 hrs by Lanthascreen TR-FRET assay
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 455.21
Compound (SMILES): O=C(c1ncnc2[nH]ccc12)C1CCCCC1
InChIKey: LXLUYBJECKDFAP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human Lck using TK-substrate-biotin as substrate incubated for 60 mins in presence of ATP by fluorescence method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 229.28, ALogP 2.72, HBA 3, HBD 1, PSA 58.64, QED 0.81
Compound (SMILES): Nc1nc(N2CCC(N3Cc4cnccc4OC[C@@H]3Cc3ccc(Cl)cc3)CC2)n[nH]1
InChIKey: OGDIGXJUZFGWNW-IBGZPJMESA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Inhibition of full length recombinant C-terminal His-taged human CHIT1 expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N',N''-diacetylchitotrioside as substrate incubated for 60 mins under shaking condition by microplate fluorometry analysis
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 439.95, ALogP 2.91, HBA 7, HBD 2, PSA 96.19, QED 0.64
Compound (SMILES): C[C@@H]1CN(c2cc(=O)n(C)c3ccc(C#N)nc23)[C@@H](C)CN1C(c1ccc(F)cc1)c1ccccc1F
InChIKey: QBLJMEHOKNLCLR-VQSPDULUSA-N
Target: Diacylglycerol kinase zeta (SINGLE PROTEIN), Homo sapiens
UniProt: Q13574
Assay: Inhibition of full length C-terminal His6tagged TVMV-His-pFBgate fused human DGK-zeta expressed in baculovirus infected Sf9 insect cells using liposome as substrate preincubated for 10 mins followed by compound addition and measured after 1 hr in presence of ATP by LIPGLO luminescence based assay
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 499.57, ALogP 4.77, HBA 6, HBD 0, PSA 65.16, QED 0.4
Compound (SMILES): CCN(CC)C(=O)c1nc(-c2nnc(C(C)(C)O)o2)sc1-c1ccc(S(=O)(=O)N[C@@H](C)C(F)(F)F)c(Cl)c1Cl
InChIKey: TZBMJMWWRPOUKP-JTQLQIEISA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to recombinant human RORgammat transfected in human HEK293T cells incubated for 24 hrs by dual-glo luciferase reporter gene assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 630.5, ALogP 5.11, HBA 9, HBD 2, PSA 138.52, QED 0.33
Compound (SMILES): COC(=O)C1=Cc2cc(OC)ccc2OC(=O)C1
InChIKey: AOGASQZTIZEMJW-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 assessed as inhibitory constant incubated for 6 hrs by stopped-flow CO2 hydration assay
Measurement: Ki = 66818 nM (pChEMBL 4.170000076293945)
Descriptors: MW 248.23, ALogP 1.56, HBA 5, HBD 0, PSA 61.83, QED 0.59
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)N2CCC[C@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)cc1
InChIKey: RUBYHLPRZRMTJO-FLVSMNSFSA-N
Target: Cyclin-dependent kinase 13/Cyclin-K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant CDK13/Cyclin K (unknown origin) expresssed in baculovirus infected insect cells using peptide substrate incubated for 30 mins in presence of [32P]gamma-ATP by scintillation counter method
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 558.09, ALogP 5.05, HBA 6, HBD 3, PSA 106.25, QED 0.26
Compound (SMILES): CSc1nc2ccccc2n1-c1csc(NC/C(C)=N/NC(=S)Nc2ccccc2)n1
InChIKey: ZZPGKCHSCRXXCO-VULFUBBASA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX2 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by EIA
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 467.65, ALogP 4.98, HBA 8, HBD 3, PSA 79.16, QED 0.15
Compound (SMILES): Cc1ccc(F)c(-n2ncc3c2CCC[C@H]3NC(=O)c2onc3c2CCCC3)c1
InChIKey: QCYACHGROOAKHF-QGZVFWFLSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition Assay: Assay B: Example compounds as described herein were dispensed with an acoustic liquid handler, Echo 550 (Labcyte) to a maximum volume of 50 nl per well in a 384 well plate. DHODH enzyme assays were performed with 4 nM recombinant human DHODH (purified essentially as described by Walse et. al., Biochemistry, 47, 8929-8936 (2008)). The reaction mixture consisted of 2 mM DL-dihydroorotic acid (#D7003, Sigma-Aldrich), 100 μM 3,4-dimethoxy-5-methyl-p-benzoquinone (#D9150, Sigma-Aldrich), and 200 μM 2,6-dichlorophenolindophenol sodium salt (DCIP) (#D1878, Sigma-Aldrich) in enzyme buffer (50 mM Tris-HCl pH 8.0, 0.1% Triton X-100, 150 mM KCl) in a final volume of 50 μl per well. A stock solution of 80 mM DCIP was prepared in DMSO just before use. Loss in absorbance by chromogen DCIP was measured at 595 nm at RT every 2 min for an hour with a plate reader (Envision, Perkin Elmer).
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 394.45, ALogP 3.99, HBA 5, HBD 1, PSA 72.95, QED 0.73
Compound (SMILES): COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)[C@@H](O)C[C@H](Cc1ccccc1)NC(=O)O[C@H]1CO[C@H]2OCC[C@H]21)C1CCCC1
InChIKey: ZRLPHWQOZNLOMW-NNDBWJOKSA-N
Target: Protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q9YQ12
Assay: Inhibition of HIV1 NL4-3 protease I84V mutant expressed in Escherichia coli TAP-106 cells using EDANS/DABCYL-labelled 10-amino acid containing protease cleavage site as substrate preincubated for 1 hr followed by substrate addition and measured for 60 mins by FRET assay
Measurement: Ki = 0.71 nM (pChEMBL 9.149999618530273)
Descriptors: MW 623.75, ALogP 3.48, HBA 8, HBD 4, PSA 144.45, QED 0.27
Compound (SMILES): NCCN1CCN(Cc2cc(S(N)(=O)=O)ccc2Oc2ccc(F)c(Cl)c2)CC1
InChIKey: TVIGXEOVBNMTRW-UHFFFAOYSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Agonist activity at His6-tagged-human SOS1 catalytic domain (564 to 1049 residues) expressed in Escherichia coli BL21-CodonPlus-RIPL cells assessed as increase in SOS1-mediated GDP/GTP nucleotide exchange upon K-Ras G12D mutant (1 to 169 residues) by BODIPY-GDP assay
Measurement: EC50 = 16300 nM (pChEMBL 4.789999961853027)
Descriptors: MW 442.94, ALogP 2, HBA 6, HBD 2, PSA 101.89, QED 0.68
Compound (SMILES): Nc1nc(-c2ccc(OCCN3CCOCC3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: VEASOKIYSIAFLD-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]-CCPA from human A1 receptor expressed in CHO cells
Measurement: Ki = 363.2 nM (pChEMBL 6.440000057220459)
Descriptors: MW 432.48, ALogP 1.84, HBA 9, HBD 1, PSA 99.91, QED 0.5
Compound (SMILES): C[C@H]1C[C@H]2CC(F)(F)C(N)=N[C@@]2(c2cc(NC(=O)c3cnc(OCF)cn3)ccc2F)CO1
InChIKey: QQHWYFAIJDVZQX-PVUDRZGPSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin) assessed as reduction in Abeta42 level by cell based assay
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 467.42, ALogP 3.19, HBA 7, HBD 2, PSA 111.72, QED 0.65
Compound (SMILES): CC(C(=O)NCc1cc(C(F)(F)F)nn1-c1cccc(Cl)c1)c1ccc2c(c1)CCC2
InChIKey: RVJDMXMFAJSIKI-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q704Y3
Assay: Antagonist activity at capsaicin-induced mouse TRPV1 expressed in CHOK1 cells by FLIPR assay
Measurement: Ki = 13.4 nM (pChEMBL 7.869999885559082)
Descriptors: MW 447.89, ALogP 5.45, HBA 3, HBD 1, PSA 46.92, QED 0.56
Compound (SMILES): O=C(NCc1ccc(Cl)cc1Cl)[C@@H]1CCC(=O)N1c1ccsc1
InChIKey: ARWXKCIBVKCPEZ-AWEZNQCLSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Inhibition of human P2X7 expressed in human HEK293 cells assessed as reduction in BzATP-stimulated TO-PRO-3 incorporation preincubated with compound and TO-PRO-3 for 15 mins prior to BzATP addition and measured after 1 hr by Fluo-3AM dye based flow cytometry
Measurement: IC50 = 813.2 nM (pChEMBL 6.090000152587891)
Descriptors: MW 369.27, ALogP 3.87, HBA 3, HBD 1, PSA 49.41, QED 0.89
Compound (SMILES): C[C@H](CCCOc1ccccc1Cn1c(C(F)(F)F)cnc1-c1ccc(C(F)(F)F)cc1)CC(=O)O
InChIKey: YSSLMLSKYLOHJM-MRXNPFEDSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Transactivation of GAL4-fused human PPARalpha expressed in African green monkey CV1 cells by luciferase reporter gene assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 514.47, ALogP 6.91, HBA 4, HBD 1, PSA 64.35, QED 0.24
Compound (SMILES): O=C1CCC(N2Cc3c(NC(=O)CNc4ccnc(N5CCN(c6cccc(C(F)(F)F)c6)CC5)n4)cccc3C2=O)C(=O)N1
InChIKey: DUXOGWVIPNJZCP-UHFFFAOYSA-N
Target: Protein cereblon (SINGLE PROTEIN), Homo sapiens
UniProt: Q96SW2
Assay: Binding affinity to CBRN (unknown origin) incubated for 60 mins by lenalidomide displacement assay
Measurement: Ki = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 622.61, ALogP 2.63, HBA 9, HBD 3, PSA 139.87, QED 0.34
Compound (SMILES): NC(=O)[C@@H]1CC[C@H](c2ccc(OCc3ccccc3F)cn2)N1
InChIKey: XUAXUDKRNXFTPI-CVEARBPZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 315.35, ALogP 2.08, HBA 4, HBD 2, PSA 77.24, QED 0.89
Compound (SMILES): CCS(=O)(=O)Nc1cc(-c2cn(C)c3c(=O)[nH]ccc23)cc2c1ccn2C(C)(c1ccccn1)c1ccccn1
InChIKey: LMLIBNUOIWAJFC-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of APC-labeled biotinylated-avidin from Euphorium-chelated recombinant human BRD4 bromodomain 2 expressed in Escherichia coli preincubated for 15 mins followed by APC-labeled biotinylated-avidin addition and measured after 1 hr under dark condition by TR-FRET assay
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 552.66, ALogP 4.85, HBA 7, HBD 2, PSA 114.67, QED 0.29
Compound (SMILES): Cc1[nH]c2cc(C(F)(F)F)ccc2c(=O)c1CN(C)Cc1ccccc1
InChIKey: GWYZTQXRTMPWNK-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H](+)-DTG from recombinant sigma 2 receptor (unknown origin) expressed in baculovirus infected Sf9 cell membranes after 1.5 hrs by scintillation counting analysis
Measurement: Ki = 2952 nM (pChEMBL 5.53000020980835)
Descriptors: MW 360.38, ALogP 4.49, HBA 2, HBD 1, PSA 36.1, QED 0.74
Compound (SMILES): COc1ccc(C2CCCN2Cc2ccc(Oc3ccc(C(=O)NO)cc3)cc2)cc1
InChIKey: DLQCQSHURGAKKI-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from human kappa opiod receptor expressed in CHO cells incubated for 60 mins by liquid scintillation counting method
Measurement: Ki = 179.9 nM (pChEMBL 6.75)
Descriptors: MW 418.49, ALogP 4.94, HBA 5, HBD 2, PSA 71.03, QED 0.42
Compound (SMILES): CCOC(=O)c1nc2c(C)cccc2c2c1CCC2
InChIKey: YYPVYSFNHHGCMD-UHFFFAOYSA-N
Target: Protein fosB/Transcription factor jun-D (PROTEIN COMPLEX), Homo sapiens
UniProt: P17535
Assay: Inhibition of recombinant Hi6-tagged deltaFOSB (unknown origin)/His6-tagged JUND (unknown origin) expressed in insect cells interaction with TAMRA labeled 5'-GTCGGTGACTCAAAACA-3' AP1 oligonucleotide measured after 15 mins by fluorescence polarization assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 255.32, ALogP 3.21, HBA 3, HBD 0, PSA 39.19, QED 0.77
Compound (SMILES): CN(C)Cc1ccccc1-c1cnc2c(c1)C[C@@]1(OCCCc3ccccc3)[C@H]3Cc4ccc(O)c5c4[C@@]1(CCN3CC1CC1)[C@H]2O5
InChIKey: VBHIKBZBHGDIER-YLLCFIMHSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-diprenorphine from human delta opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assay
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 627.83, ALogP 6.87, HBA 6, HBD 1, PSA 58.06, QED 0.19
Compound (SMILES): CC(C)(C)OC(=O)NCCc1c[nH]c2c1C(=O)C(c1cccnc1)=CC2=O
InChIKey: GDYNRRGPKLCYGJ-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IFNgamma-stimulated IDO1 in human HeLa cells
Measurement: EC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 367.41, ALogP 2.94, HBA 5, HBD 2, PSA 101.15, QED 0.87
Compound (SMILES): C[N+](C)(C)C[C@@H]1COC[C@](c2ccccc2)(C2CCCCC2)O1
InChIKey: UFSZYKLBZJNXLV-UXHICEINSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M2 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 13.8 nM (pChEMBL 7.860000133514404)
Descriptors: MW 318.48, ALogP 3.58, HBA 2, HBD 0, PSA 18.46, QED 0.79
Compound (SMILES): c1cc(-c2cn(CC3CC3)c3cnccc23)ccn1
InChIKey: ZMRXFXMRTUPKEB-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human His/GST-tagged GSK3beta (2 to 433 residues) expressed in baculovirus infected Sf9 cells using Ulight-glycogen synthase peptide as substrate incubated for 30 mins by TR-FRET LANCE method
Measurement: IC50 > 8300 nM (pChEMBL 5.080999851226807)
Descriptors: MW 249.32, ALogP 3.51, HBA 3, HBD 0, PSA 30.71, QED 0.71
Compound (SMILES): CCC(C)N1c2ccccc2C(=O)N(C)c2cnc(Nc3ccc(N4CCN(C)CC4)cc3OC)nc21
InChIKey: WWDLVMCJDNTBPK-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of recombinant human GST-tagged LRRK2 catalytic domain (970 to 2527 residues) expressed in baculovirus expression system using LRRKtide as substrate measured after 1 hr by Alexa fluor-647 ADP tracer-based ADAPTA assay
Measurement: IC50 = 743 nM (pChEMBL 6.130000114440918)
Descriptors: MW 501.64, ALogP 4.51, HBA 8, HBD 1, PSA 77.07, QED 0.53
Compound (SMILES): CN(Cc1ccc(-c2ccccc2)cc1)C1CN(C#N)C1
InChIKey: AKLYMSKSAPLCHJ-UHFFFAOYSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition Assay: In order to have an assay method more conducive to high-throughput screening than those published for measuring the NAE hydrolyzing activity of NAAA, we developed the fluorogenic PEA analog N-(4-methyl coumarin)palmitamide (PAMCA), which is hydrolyzed to fluorescent 7-amino-4-methyl coumarin (AMC) and palmitic acid. For three point concentration inhibition assays with hNAAA the following procedure is used. Purified activated NAAA (final concentration of 0.25 μg/mL) is incubated in assay buffer (100 mM citrate-phosphate buffer, pH 4.5, 3 mM DTT, 0.1% Triton X-100, 0.05% BSA, and 150 mM NaCl) made up to a total volume of 180 μL, followed by addition of the compound dissolved in 10 μL DMSO (along with DMSO neat for the control sample) with the final concentrations for each compound of 100, 10, and 1 μM, in triplicate on a 96 well plate. These samples are allowed to incubate for 15 min at room temperature and then 10 μL of a PAMCA stock solution in DMSO (final PAMCA concentration [5 μM]) was added. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes, with fluorescence readings taken every 10 minutes at a wavelength of 460 nm (using an excitation wavelength of 360 nm) on a Synergy HT Plate Reader using Gen5 software from Bio-Tek. The enzyme activity is calculated by converting the relative fluorescence units to AMC formed, using a standard curve of AMC. For compounds that inhibit hNAAA in range IC50 <1 μM full inhibition curves using eight different concentrations of inhibitor (8 point assay) are generated. The assay procedure used is the same as the three point assay. For ostensibly covalent compounds (as observed by a significant decrease in the slope of a plot of fluorescence vs. time in three point screen) samples are allowed to incubate for 2 hours at 37° C., instead of 15 minutes, before addition of 10 μL of a PAMCA stock solution in DMSO for a final PAMCA concentration of 5 μM. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes Inhibition constants are calculated using pro Fit software (Quantum Soft, Uetikon am See, Switzerland) and a Levenberg-Marquardt algorithm.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 277.37, ALogP 2.95, HBA 3, HBD 0, PSA 30.27, QED 0.8
Compound (SMILES): O=C1CC(S)C(=O)N1c1ccc(Cl)c(Cl)c1
InChIKey: MBMARGKNQVOHBM-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human HDAC3 expressed in insect cells using R-H-K-K(Ac)-AFC as substrate by fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 276.14, ALogP 2.56, HBA 3, HBD 1, PSA 37.38, QED 0.63
Compound (SMILES): O=C1[C@@H]2Cc3c([nH]c4ccccc34)[C@H](c3ccc(F)cc3)N2C(=O)N1c1cccc(C(F)(F)F)c1
InChIKey: BKIVSJZNZNFDNY-GMAHTHKFSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 expressed in HEK-293/TRPM8 exon1 K3 cells assessed as inhibition of menthol-induced current response by whole-cell voltage clamp method
Measurement: IC50 = 7.67 nM (pChEMBL 8.119999885559082)
Descriptors: MW 479.43, ALogP 5.81, HBA 2, HBD 1, PSA 56.41, QED 0.29
Compound (SMILES): O=S(=O)(Nc1ncccn1)c1ccc2c(c1)OCC[C@@H]2c1ccc(C(F)(F)F)cc1-c1ccc(F)cc1
InChIKey: CZZSYEPBDUZHLQ-OAQYLSRUSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin) expressed in HEK293 cells assessed as reduction in veratridine-induced depolarization preincubated for 15 to 20 mins followed by veratridine stimulation by 1X red membrane potential dye based FLIPR assay
Measurement: IC50 = 1069 nM (pChEMBL 5.96999979019165)
Descriptors: MW 529.52, ALogP 6.02, HBA 5, HBD 1, PSA 81.18, QED 0.32
Compound (SMILES): Cc1cccc(C(=O)Nc2nc3ccccc3s2)c1
InChIKey: RFPQSFCICWNNNL-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Inhibition of SCD in human H2009 cells non-expressing CYP4F11 assessed as reduction in cell viability incubated for 96 hrs by cell titer Glo reagent based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 268.34, ALogP 3.86, HBA 3, HBD 1, PSA 41.99, QED 0.77
Compound (SMILES): Nc1nc(N2CCC(N3Cc4cc(F)ccc4OC[C@@H]3Cc3ccc(Cl)cc3)CC2)n[nH]1
InChIKey: QOZFARNLHIXLOT-FQEVSTJZSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Inhibition of full length recombinant C-terminal His-tagged human acidic mammalian chitinase expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N-diacetylchitobioside hydrate as substrate incubated for 60 mins under shaking condition by microplate fluorometry analysis
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 456.95, ALogP 3.65, HBA 6, HBD 2, PSA 83.3, QED 0.62
Compound (SMILES): CN1CN(C(=O)CSc2ncnc3c(C4CC4)c(Cl)sc23)CC1=O
InChIKey: ZMTMICOXUWYQAD-UHFFFAOYSA-N
Target: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Inhibition of NOTUM (unknown origin) transfected in human HEK293T cells harbouring TCF/LEF luciferase reporter gene assessed as activation of Wnt signalling pathway incubated for 10 mins followed by wnt-3A addition and further incubated for 1 hr by steady-glo luciferase assay
Measurement: EC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 382.9, ALogP 2.57, HBA 6, HBD 0, PSA 66.4, QED 0.6
Compound (SMILES): CC(C)(C)c1cc(Nc2nc(N3CCC[C@H](N)C3)ncc2C(N)=O)cc(C(C)(C)C)c1
InChIKey: CZRHQTSOTFWKCN-KRWDZBQOSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13163
Assay: Inhibition of human MEK5 using ERK5 as substrate in presence of [gamma-33P]-ATP by hotspot kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 424.59, ALogP 3.84, HBA 6, HBD 3, PSA 110.16, QED 0.69
Compound (SMILES): [O-][S+]1CC(Nc2nonc2/C(=N/O)Nc2ccc(F)c(Br)c2)C1
InChIKey: ISGARSAEPGCOHC-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFN-gamma stimulated human HeLa cells assessed as reduction in kynurenine formation using L-tryptophan as substrate incubated for 24 hrs by UV-spectrophotometry
Measurement: EC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 404.22, ALogP 1.76, HBA 7, HBD 3, PSA 118.63, QED 0.23
Compound (SMILES): N#Cc1ccn2c(=O)n(CCCCN3CCN(c4cccc5sccc45)CC3)nc2c1
InChIKey: XRZZROKCQWOAAH-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Agonist activity at 5HT1A receptor (unknown origin) by calcium-dye based FLIPR assay
Measurement: EC50 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 432.55, ALogP 3.18, HBA 8, HBD 0, PSA 69.57, QED 0.44
Compound (SMILES): Brc1ccc2nc(-c3ccccc3)[nH]c2c1
InChIKey: GVFCYTFUNNARML-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 catalytic domain (Phe99 to Gln269 residues) expressed in Escherichia coli cells using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2/TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6'-TAMRA)-Ala-Lys-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 273.13, ALogP 3.99, HBA 1, HBD 1, PSA 28.68, QED 0.71
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)CNCCCCCN(CC[C@H](N)C(=O)O)C[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O)C(=O)N[C@@H](C)C(N)=O
InChIKey: KBILEXHGJAGPLF-TWFREJTOSA-N
Target: N-terminal Xaa-Pro-Lys N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV86
Assay: Binding affinity to NTMT1 (unknown origin) assessed as binding constant Kd2 by ITC assay
Measurement: Kd = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 1075.29
Compound (SMILES): Cc1cc(-c2ccc(=O)n(C)c2C)cc2cn(C3CCCNC3)nc12
InChIKey: BTDJRWBEFFLSBI-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Antagonist activity at TLR8 in human PBMC assessed as inhibition of DOTAP-ssRNA40 induced TNFalpha production preincubated for 30 mins followed by ssRNA40 addition measured after 20 hrs by HTRF assay
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 336.44, ALogP 2.94, HBA 5, HBD 1, PSA 51.85, QED 0.78
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3CC(=O)Nc2ccc(Cl)cc2Cl)cc(OC)c1OC
InChIKey: KGALHZAKVBFVKT-LDLYASANSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 536.46, ALogP 4.77, HBA 6, HBD 2, PSA 89.13, QED 0.51
Compound (SMILES): Nc1nc(N2CCC(N3Cc4cccnc4OC[C@@H]3Cc3ccc(Cl)cc3)CC2)n[nH]1
InChIKey: ANKHSKJBBNXMRM-IBGZPJMESA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Inhibition of full length recombinant C-terminal His-taged human CHIT1 expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N',N''-diacetylchitotrioside as substrate incubated for 60 mins under shaking condition by microplate fluorometry analysis
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 439.95, ALogP 2.91, HBA 7, HBD 2, PSA 96.19, QED 0.64
Compound (SMILES): C=CCN1CCc2cc(OC)c(O)cc2C(c2ccccc2Br)C1
InChIKey: CDMIXJWMVYRCRT-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]SCH23390 from dopamine D5 receptor (unknown origin)
Measurement: Ki = 501 nM (pChEMBL 6.300000190734863)
Descriptors: MW 388.31, ALogP 4.34, HBA 3, HBD 1, PSA 32.7, QED 0.79
Compound (SMILES): O=C(COc1cccc(-c2nc3c(c(Nc4ccc(-c5cn[nH]c5)cc4)n2)COC3)c1)NC1CC1
InChIKey: RYJMJCJWMWMLJV-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11169
Assay: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay
Measurement: IC50 = 238 nM (pChEMBL 6.619999885559082)
Descriptors: MW 468.52, ALogP 3.96, HBA 7, HBD 3, PSA 114.05, QED 0.36
Compound (SMILES): O=C(O)C(=O)Nc1cccc(C#Cc2ccccc2)c1
InChIKey: HOPJPRTYNRLPHK-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 265.27, ALogP 2.11, HBA 2, HBD 2, PSA 66.4, QED 0.61
Compound (SMILES): COC(=O)[C@H](Cc1ccccc1)Nc1nc(Cl)nc(Nc2ccc(N3CCOCC3=O)cc2)n1
InChIKey: OAULFGKSACZQQH-SFHVURJKSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX2 using arachidonic acid as substrate incubated for 10 mins followed by substrate addition and measured after 2 mins by EIA assay
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 482.93, ALogP 2.83, HBA 9, HBD 2, PSA 118.57, QED 0.47
Compound (SMILES): CN[C@@H](C)C(=O)N[C@H](C(=O)N1C[C@@H](NC(=O)CCOCCOCCOCCNC(=O)CN2CCN(c3ccc(Nc4ncc5c(C)c(C(C)=O)c(=O)n(C6CCCC6)c5n4)nc3)CC2)C[C@H]1C(=O)Nc1c(F)cccc1F)C(C)(C)C
InChIKey: DNVODRITWXGBQB-TXCNDJKGSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of human CDK6/cyclin-D3 using RB protein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 1130.31
Compound (SMILES): CNC(=O)c1cc(C(=O)NC2CCC2)cn(Cc2ccccn2)c1=O
InChIKey: MLFFOMPRQYXUFM-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to 6His-Thr-BRD4 (1 to 477 residues) BD1 domain (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 340.38, ALogP 0.93, HBA 5, HBD 2, PSA 93.09, QED 0.85
Compound (SMILES): CCOC(=O)c1[nH]c(C)c(Cc2ccc(OC)cc2)c1C
InChIKey: VZQQHRJTOPINCI-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Mus musculus
UniProt: O35435
Assay: Inhibition of C-terminal His6-tagged mouse DHODH expressed in Escherichia coli BL21(DE3) cells using L-DHO as substrate by DCIP dye based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 287.36, ALogP 3.41, HBA 3, HBD 1, PSA 51.32, QED 0.86
Compound (SMILES): CC/C(=C\c1ccccc1)[C@@H]1C[C@H]1NC1CC2(C1)CN(CC(F)F)C2
InChIKey: OJNIRUHGOPLXSD-XLRIHDRJSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of recombinant N-terminal His-tagged LSD1 (unknown origin) expressed in Escherichia coli expression system using ART-K(Me1)-QTARKSTGGKAPRKQLAGGK(Biotin) as substrate incubated for 60 mins by TR-FRET assay
Measurement: IC50 < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 346.47, ALogP 4.19, HBA 2, HBD 1, PSA 15.27, QED 0.8
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5ccncn5)cc4C[C@@]4(OCCCc5ccccc5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: VEHJGWOVJCGIDX-LMUOQGPPSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-diprenorphine from human delta opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assay
Measurement: Ki = 22.1 nM (pChEMBL 7.659999847412109)
Descriptors: MW 572.71, ALogP 5.6, HBA 7, HBD 1, PSA 80.6, QED 0.28
Compound (SMILES): CSc1nc2ccccc2n1-c1csc(NC(=O)c2ccc(Cl)cc2)n1
InChIKey: XRBQILGSUZQQNV-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX2 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by EIA
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 400.92, ALogP 5.11, HBA 6, HBD 1, PSA 59.81, QED 0.48
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3CC[C@H](C(=O)NC4CC4)CC3)c12
InChIKey: BBVXXRFQYGRLLY-XYPYZODXSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of N-terminal His-tagged human JAK2 catalytic domain incubated for 20 mins in presence of TK substrate-biotin by TR-FRET assay
Measurement: IC50 = 9400 nM (pChEMBL 5.03000020980835)
Descriptors: MW 314.39, ALogP 2.11, HBA 3, HBD 3, PSA 90.64, QED 0.81
Compound (SMILES): O=C(O)C(=O)Nc1ccc(C#Cc2ccc(O)cc2)cc1
InChIKey: CZUQDWSZRALHID-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of SHP2 (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 281.27, ALogP 1.82, HBA 3, HBD 3, PSA 86.63, QED 0.55
Compound (SMILES): CSCC[C@@H]1NC(=O)[C@@H](NC(=O)[C@H](CCCCNC(C)=S)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2c[nH]cn2)NC(C)=O)Cc2ccc(cc2)OCCCCCCCCCCNC1=O
InChIKey: SLSRNUCBVSLFMN-LSLOANPCSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of His6-tagged human SIRT2 deacetylation activity using SIRT1 acetyl-lysine as substrate in presence of beta-NAD+ after 12 mins by reversed-phase HPLC analysis
Measurement: IC50 = 17900 nM (pChEMBL 4.75)
Descriptors: MW 943.29, ALogP 3.26, HBA 11, HBD 9, PSA 250.56, QED 0.06
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nnc(-c3ccccc3Cl)o2)cc1
InChIKey: AIJJVGNYPUUODB-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 using 4-NPA as substrate measured for 3 mins by spectrophotometry
Measurement: Ki = 8.65 nM (pChEMBL 8.0600004196167)
Descriptors: MW 335.77, ALogP 2.7, HBA 5, HBD 1, PSA 99.08, QED 0.79
Compound (SMILES): CCCN1CCc2cccc3c2C1Cc1ccc2nc(N)sc2c1-3
InChIKey: OGXZFBZWKSYKCH-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from human 5-HT7A receptor expresssed in stable HEK cell membrane incubated for 90 mins by microbeta counting method
Measurement: Ki = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 335.48, ALogP 4.41, HBA 4, HBD 1, PSA 42.15, QED 0.75
Compound (SMILES): Nc1nc(N2CCC(N(CCc3ccc(Cl)cc3)Cc3cccc(Cl)c3)CC2)n[nH]1
InChIKey: VFNPFRJQILTIIZ-UHFFFAOYSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Inhibition of full length recombinant C-terminal His-taged human CHIT1 expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N',N''-diacetylchitotrioside as substrate incubated for 60 mins under shaking condition by microplate fluorometry analysis
Measurement: IC50 = 176 nM (pChEMBL 6.75)
Descriptors: MW 445.4, ALogP 4.41, HBA 5, HBD 2, PSA 74.07, QED 0.56
Compound (SMILES): O=C1N[C@H](Cc2ccccc2)C(=O)N2Cc3[nH]c4ccccc4c3C[C@@H]12
InChIKey: RADKAGRBIKGFHM-MJGOQNOKSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Antagonist activity at human TRPM8 expressed in HEK-293/TRPM8 exon1 K3 cells assessed as inhibition of menthol-induced current response by whole-cell voltage clamp method
Measurement: IC50 = 6.57 nM (pChEMBL 8.180000305175781)
Descriptors: MW 345.4, ALogP 2.16, HBA 2, HBD 2, PSA 65.2, QED 0.75
Compound (SMILES): CCOc1cc(Cl)c(-c2ccc(-c3nc4ccccc4s3)c(=O)[nH]2)cc1N1CCOCC1
InChIKey: JUEGORAEZRDVPB-UHFFFAOYSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Displacement of [125I]-ghrelin from human GHS-R1a stably expressed in HEK cell membrane measured after 60 mins by gamma counter method
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 467.98, ALogP 5.21, HBA 6, HBD 1, PSA 67.45, QED 0.44
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3cc(CC(C)(C)C(=O)O)on3)nc2CC2CCC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: ISWGZOZQPRMRJA-LBPRGKRZSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to recombinant human RORgammat transfected in human HEK293T cells incubated for 24 hrs by dual-glo luciferase reporter gene assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 640.53, ALogP 7, HBA 7, HBD 2, PSA 122.39, QED 0.24
Compound (SMILES): COc1ccc(CN2[C@@H]3CCC[C@H]2C[C@H](NC(=O)c2cc(OC)c(OC)c(OC)c2)C3)cc1
InChIKey: DCBRWARWIDLMFD-MZADTFQBSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 454.57, ALogP 4.04, HBA 6, HBD 1, PSA 69.26, QED 0.65
Compound (SMILES): Cc1cn(-c2cc(NC(=O)c3ccc(C)c(Oc4ccccc4)c3)cc(N3CCN(C)CC3)c2)cn1
InChIKey: TYKXIBLBQNRTJM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of recombinant human N-terminal His-tagged Abl (2 to 1130 residues) expressed in baculovirus expression system using FAM-labelled P2 peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr in presence of ATP by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 481.6, ALogP 5.29, HBA 6, HBD 1, PSA 62.63, QED 0.41
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nnc(-c3ccc4ccccc4c3)o2)cc1
InChIKey: ILZLUQDILSPWQN-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 using 4-NPA as substrate measured for 3 mins by spectrophotometry
Measurement: Ki = 5.15 nM (pChEMBL 8.289999961853027)
Descriptors: MW 351.39, ALogP 3.2, HBA 5, HBD 1, PSA 99.08, QED 0.61
Compound (SMILES): CN(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)C(=O)c1c(OCCOCc2ccccc2)c2ccccc2n(C)c1=O
InChIKey: SJQCSSCACGCTEU-UHFFFAOYSA-N
Target: Phosphatidylcholine:ceramide cholinephosphotransferase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q9D4B1
Assay: Inhibition of mouse recombinant C-terminal FLAG-tagged SMS2 expressed in mammalian expression system using C14-phosphatidylcholineD72 and C17-ceramide pre-incubated for 60 mins followed by incubation with substrate for 30 mins measured by RapidFire/MS assay
Measurement: IC50 = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 592.54, ALogP 6.44, HBA 5, HBD 0, PSA 60.77, QED 0.17
Compound (SMILES): O=c1n(CCCCN2CCN(c3cccc4sc(F)cc34)CC2)nc2c(F)cccn12
InChIKey: NUMVELFDJZDMIW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Agonist activity at 5HT1A receptor (unknown origin) by calcium-dye based FLIPR assay
Measurement: EC50 = 1.53 nM (pChEMBL 8.8100004196167)
Descriptors: MW 443.52, ALogP 3.59, HBA 7, HBD 0, PSA 45.78, QED 0.43
Compound (SMILES): c1cn2cc(-c3cnc4nc[nH]c4c3)nc(Nc3ccc(N4CCN(C5COC5)CC4)cc3)c2n1
InChIKey: IYHYHWYQMUPPKT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK in human Ramos cells assessed as reduction in antihuman IgM F(ab)2-induced phosphorylation of BLNK at Y96 residue preincubated for 1 hr followed by antihuman IgM F(ab)2 stimulation for 5 mins by MSD high bind plate assay
Measurement: EC50 = 286 nM (pChEMBL 6.539999961853027)
Descriptors: MW 467.54, ALogP 2.93, HBA 9, HBD 2, PSA 99.5, QED 0.41
Compound (SMILES): O=C(O)C(=O)Nc1ccc(C#Cc2ccc(C(F)(F)F)cc2C(F)(F)F)cc1
InChIKey: FPBMEPDXSNHHAK-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of SHP2 (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 401.26, ALogP 4.15, HBA 2, HBD 2, PSA 66.4, QED 0.43
Compound (SMILES): N#CCCN(CCc1ccccc1)CC(=O)N(CCc1ccccc1)CCc1ccc(S(N)(=O)=O)cc1
InChIKey: XZPNEWBDLFUWEA-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki = 368.5 nM (pChEMBL 6.429999828338623)
Descriptors: MW 518.68, ALogP 3.41, HBA 5, HBD 1, PSA 107.5, QED 0.35
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc(Cl)c(NCc4ccc(F)cc4)n3)nc2)CC1
InChIKey: MOYSDHLSIFKCBQ-UHFFFAOYSA-N
Target: CDK9/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 427.92, ALogP 3.77, HBA 7, HBD 2, PSA 69.21, QED 0.62
Compound (SMILES): CNCCN1CCC(c2ccc3[nH]c(-c4ccccc4OC)c(C)c3c2)CC1
InChIKey: OEMNTKPTIVGFFI-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 overexpressed in HEK-Blue cells assessed as inhibition of gardiquimod-induced NFkappaB and AP-1 activation preincubated for 30 mins followed by gardiquimod stimulation measured after 22 hrs by quanti-blue SEAP assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 377.53, ALogP 4.55, HBA 3, HBD 2, PSA 40.29, QED 0.66
Compound (SMILES): CCCCCn1c(=O)c(C(=O)NC23CC4CC(CC(C4)C2)C3)c(O)c2nn(C)cc21
InChIKey: AMKLUVRBVSQTDG-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP-55,940 from recombinant human CB2R expressed in HEK293 cell membranes
Measurement: Ki = 0.18 nM (pChEMBL 9.739999771118164)
Descriptors: MW 412.53, ALogP 3.33, HBA 6, HBD 2, PSA 89.15, QED 0.71
Compound (SMILES): CC(C)[C@@H](NC(=O)c1cc(C(F)(F)F)ccc1F)C(=O)N1CCC2(CC1)C(=O)N(C)C(=O)N2c1ccc(C(=O)O)cc1
InChIKey: CWSQVYFGLYCBFT-OAQYLSRUSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Autotaxin LPC Cascade Assay: The efficacy of the Examples described herein, as inhibitors of ATX are demonstrated and confirmed by pharmacological in vitro assays. The following assays and their respective methods are carried out with the compounds according to the present invention. Activity possessed by the compounds may be demonstrated in vivo. Those skilled in the art will appreciate that a variety of assay formats may be used to determine the activity of the compounds of this invention.Autotaxin LPC Cascade Assay:Assay Buffer:100 mM Tris-HCl, pH=9500 mM NaCl5 mM MgCl25 mM CaCl20.05% Triton X 100Reagents:Enzyme Source Stock conc Working conc. Final conc. Autotaxin X-Chem 4.6 μM 20 nM 5 nM LPC Sigma L5254 8 mM in assay buffer 400 μM 100 μM Choline Oxidase Sigma C5896 50 U/mL in water 0.8 U/mL 0.1 U/mL HRP Sigma P8375 1000 U/mL in water 8 U/mL 1 U/mL Ampliflu Red Sigma 90101 100 mM in DMSO 400 μM 50 μM.
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 592.55, ALogP 3.76, HBA 5, HBD 2, PSA 127.33, QED 0.39
Compound (SMILES): CSc1cc(C)[nH]c(=O)c1CNC(=O)c1c(C)n([C@H](C)[C@H]2OC[C@H](N(C)C)CO2)c2ccccc12
InChIKey: RXEFDCRIMMUMCM-UYPAYLBCSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 in human HeLa cells assessed as inhibition of trimethylation of H3K27 after 72 hrs by AlphaLISA assay
Measurement: EC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 498.65, ALogP 3.46, HBA 7, HBD 2, PSA 88.59, QED 0.49
Compound (SMILES): Cc1cc(Cl)cc(-c2ccnc3cc(Cn4c(=O)ccn(CC(F)(F)F)c4=O)sc23)c1O[C@@H]1CCNC[C@@H]1C
InChIKey: AAWWECJHPHXAGX-KSFYIVLOSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of USP7 in human RKO cells transfected with p53 luciferase reporter vector assessed as increase in p53-dependent luciferase activity measured after 18 hrs by BrightGlo luciferase assay
Measurement: EC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 579.04, ALogP 5.24, HBA 8, HBD 1, PSA 78.15, QED 0.34
Compound (SMILES): C#Cc1ccc(NC(=O)C(=O)O)cc1
InChIKey: HAMKIEUBXUECIL-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 189.17, ALogP 0.69, HBA 2, HBD 2, PSA 66.4, QED 0.5
Compound (SMILES): CCn1cnc2c(NCc3nc4ccc(F)c(F)c4[nH]3)nc(N3CCCC[C@H]3CCO)nc21
InChIKey: HVFVQLFPRQYJTR-ZDUSSCGKSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) in presence of high ATP
Measurement: IC50 > 28000 nM (pChEMBL 4.552999973297119)
Descriptors: MW 456.5, ALogP 3.35, HBA 8, HBD 3, PSA 107.78, QED 0.39
Compound (SMILES): N#CN=S(=O)(NC(=O)Nc1c2c(cc3c1CCC3)CCC2)c1ccccn1
InChIKey: GDAHMFIDUIIGMC-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 inflammasome activation in LPS-primed human THP1 cells assessed as reduction in TNF alpha level preincubated for 1 hr followed by addition of monosodium urate crystals further incubated for 16 hrs and measured post monosodium urate crystals addition 1 hr by ELISA method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 381.46, ALogP 3.1, HBA 5, HBD 2, PSA 107.24, QED 0.8