lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cc(OCC)cc(P(=O)(OCOC(C)=O)OCOC(C)=O)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: DWWMNBWBWLGDNW-KAYWLYCHSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 697.68, ALogP 3.86, HBA 13, HBD 3, PSA 209.24, QED 0.03
Compound (SMILES): O=C(NO)c1ccc(N(Cc2ccc(C(F)(F)F)cc2)C(=O)CN(Cc2ccccc2C(F)(F)F)S(=O)(=O)c2ccc(F)c(F)c2)cc1
InChIKey: MPRCLKOXHHCIRF-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of recombinant human HDAC11 expressed in SF9 baculoviral system using FAM-labeled acetylated peptide as substrate by EMSA
Measurement: IC50 = 396 nM (pChEMBL 6.400000095367432)
Descriptors: MW 701.59, ALogP 6.55, HBA 5, HBD 2, PSA 107.02, QED 0.11
Compound (SMILES): COc1cc2c(cc1OC)[C@H](c1ccc(F)cc1)N(C(=O)N1CCc3cc(OC)c(OC)cc3[C@@H]1c1ccc(F)cc1)CC2
InChIKey: BHCFMOBCNHFBGR-HEVIKAOCSA-N
Target: Heat sensitive channel TRPV3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q4QYD9
Assay: Antagonist activity at recombinant rat TRPV3 expressed in HEK293 cells assessed as inhibition of thymol-induced intracellular calcium accumulation preincubated for 5 mins followed by thymol addition by Fluo-4-AM probe-based spectrofluorimetric assay
Measurement: IC50 = 72900 nM (pChEMBL 4.139999866485596)
Descriptors: MW 600.66, ALogP 6.71, HBA 5, HBD 0, PSA 60.47, QED 0.25
Compound (SMILES): CCCCNC(=O)c1cc(S(N)(=O)=O)c(Br)cc1S(=O)(=O)c1ccccc1
InChIKey: FATAPRQFXGZRGG-UHFFFAOYSA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 7100 nM (pChEMBL 5.150000095367432)
Descriptors: MW 475.39, ALogP 2.46, HBA 5, HBD 2, PSA 123.4, QED 0.6
Compound (SMILES): COC[C@H]1C[C@@H](c2nc3ccc4cc5c(cc4c3[nH]2)OCc2cc(-c3cnc([C@@H]4C[C@H](C)CN4C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]3)ccc2-5)N(C(=O)[C@@H](NC(=O)OC)C(C)C)C1
InChIKey: QRKFUUOTBBROJV-SORRNWNHSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 3a S52 infected in human HuH7 transient chimeric replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.058 nM (pChEMBL 10.239999771118164)
Descriptors: MW 849, ALogP 6.87, HBA 10, HBD 4, PSA 193.1, QED 0.11
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCCN3Cc2cc(F)c(F)c(F)c2)n(C)c1=O
InChIKey: MUHRBGXNPOMMBL-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAOB expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured over 45 mins by horseradish peroxidase-Amplex Red-coupled fluorometric assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 379.34, ALogP 1.26, HBA 7, HBD 0, PSA 65.06, QED 0.63
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1ccc(C(c2ccccc2)c2ccccc2)s1)C(=O)O
InChIKey: XYFDAJRUBYOTRD-SFHVURJKSA-N
Target: C3a anaphylatoxin chemotactic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16581
Assay: Antagonist activity at C3a receptor in human MDM cells assessed as inhibition of C3a-induced intracellular calcium release preincubated for 30 mins followed by C3a addition and measured at 1 sec interval for => 200 secs by Fluo-3 AM dye-based FLIPR assay
Measurement: IC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 450.56, ALogP 3.37, HBA 4, HBD 5, PSA 128.3, QED 0.18
Compound (SMILES): OC(CC1c2c(F)cccc2-c2cncn21)C1CCC(F)(F)CC1
InChIKey: FPKRCRNJVIHTNG-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 336.36, ALogP 4.17, HBA 3, HBD 1, PSA 38.05, QED 0.91
Compound (SMILES): Fc1ccccc1-c1cc(Nc2ccncc2)c2cc[nH]c2n1
InChIKey: ICADYKQQHFVDME-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of ALK5 (unknown origin) using fluorescein-labeled peptide substrate incubated for 90 mins by TR-FRET assay
Measurement: Kd = 10 nM (pChEMBL 8)
Descriptors: MW 304.33, ALogP 4.51, HBA 3, HBD 2, PSA 53.6, QED 0.59
Compound (SMILES): CC(C)(C)c1ccc(CN2CCN(S(=O)(=O)Nc3ccc(SCCc4ccccc4)cc3C(=O)O)CC2)cc1
InChIKey: WIWNZUYJVZDDEH-UHFFFAOYSA-N
Target: Bcl-2-related protein A1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16548
Assay: Binding affinity to immobilized biotin-labeled and N-terminal His6-tagged human Bfl-1 (1 to 151 residues), expressed in Escherichia coli Rosetta2 DE3 by biolayer interferometry
Measurement: Kd = 1270 nM (pChEMBL 5.900000095367432)
Descriptors: MW 567.78, ALogP 5.49, HBA 5, HBD 2, PSA 89.95, QED 0.32
Compound (SMILES): OCc1cccc(-c2ccc3nc(-c4ccc(Cl)cc4)cn3c2)c1
InChIKey: IHUPABWARJLUMA-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 4 group A member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P43354
Assay: Agonist activity at full-length Gal4-fused NOT (unknown origin) expressed in CHO cells by luciferase reporter gene assay
Measurement: EC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 334.81, ALogP 4.81, HBA 3, HBD 1, PSA 37.53, QED 0.58
Compound (SMILES): COC1Cc2ccccc2[C@]2(CC[C@@H](N(C)CC3CCCCC3)CC2)O1
InChIKey: MBRMOGQHSBUGKH-FXCIWXGGSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from delta opioid receptor in rat membranes after 120 mins by scintillation counting analysis
Measurement: Ki = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 357.54, ALogP 4.88, HBA 3, HBD 0, PSA 21.7, QED 0.77
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: VAGFPILJLLZTKR-ISSCZAFUSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60896
Assay: Displacement of [125I]-labeled rat amylin from human amylin receptor expressed in BHK tkts13 whole cells co-expressing RAMP3 incubated for 60 mins by scintillation proximity assay
Measurement: IC50 = 0.588 nM (pChEMBL 9.229999542236328)
Descriptors: MW 3736.23
Compound (SMILES): CCCCCn1/c(=N/C(=O)c2ccc(C(F)(F)F)cc2)sc2ccccc21
InChIKey: ZKQOBFAUDJCQMQ-CLCOLTQESA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at N-terminal Flag epitope tagged CB1 (unknown origin) expressed in HTLA cells assessed as increase of beta-arrestin recruitment by Tango assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 392.45, ALogP 5.65, HBA 3, HBD 0, PSA 34.36, QED 0.52
Compound (SMILES): O=C(O)c1ccc(-n2cc(C(=O)c3c(Cl)cccc3C(F)(F)F)c3c(F)cccc32)cc1
InChIKey: CWHKOHWOAVTDCW-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated for 5 mins followed by NADPH addition measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 461.8, ALogP 6.37, HBA 3, HBD 1, PSA 59.3, QED 0.28
Compound (SMILES): CO[C@H](CN1CC[C@@]2(C)c3cc(O)ccc3C[C@@H]1[C@@H]2C)c1ccccc1
InChIKey: CYJVECUASMVXNS-RAKGIWIYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at Rluc-tagged MOR receptor (unknown origin) expressed in human SH-5YSY cells co-expressing RGFP-fused to MOR/beta-arrestin-2 assessed as increase in MOR/beta-arrestin-2 protein interaction incubated for 5 mins in presence of coelenterazine by BRET assay
Measurement: EC50 = 151.36 nM (pChEMBL 6.820000171661377)
Descriptors: MW 351.49, ALogP 4.3, HBA 3, HBD 1, PSA 32.7, QED 0.89
Compound (SMILES): COc1ccc(NC(=O)c2cccc(-c3nc(NC(P(=O)(O)O)P(=O)(O)O)c4ccsc4n3)c2)cc1F
InChIKey: XPPGEOUCUMGOGK-UHFFFAOYSA-N
Target: Farnesyl pyrophosphate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: P14324
Assay: Inhibition of human FPPS expressed in Escherichia coli BL21 (DE3) preincubated for 10 mins in presence compound relative to control
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 568.42, ALogP 3.81, HBA 8, HBD 6, PSA 191.2, QED 0.17
Compound (SMILES): Cc1cc(S(N)(=O)=O)c(C)cc1N1CC(C(=O)O)CC1=O
InChIKey: MTHLUECOFDPPBS-UHFFFAOYSA-N
Target: Carbonic anhydrase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P23280
Assay: Binding affinity to recombinant human CA6 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 312.35, ALogP 0.39, HBA 4, HBD 2, PSA 117.77, QED 0.84
Compound (SMILES): O=C(/C=C/c1cccn(CCc2ccc3ccccc3c2)c1=O)NO
InChIKey: XQXZIMLBLPDARP-MDZDMXLPSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant full-length human HDAC4 using Boc-Lys(trifluoroacetyl)-AMC as substrate measured after 2 hrs by fluorescence assay
Measurement: IC50 = 14624.7 nM (pChEMBL 4.829999923706055)
Descriptors: MW 334.38, ALogP 2.76, HBA 4, HBD 2, PSA 71.33, QED 0.43
Compound (SMILES): CC(=O)C1=C(O)C(=O)N(c2ccc(Br)cc2F)C1C1CCCCC1
InChIKey: ARZUMHIABDHPTN-UHFFFAOYSA-N
Target: C-C chemokine receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32246
Assay: Displacement of [3H]-CCR2-RA-[R] from human TEV protease site linked CCR1 expressed in human U20S cell membranes co-expressing Gal4-VP16 transcription factor after 120 mins by scintillation spectrometry
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 396.26, ALogP 4.28, HBA 3, HBD 1, PSA 57.61, QED 0.83
Compound (SMILES): CCCN(CCCCNC(=O)c1cc2ccccc2[nH]1)CC1CC1c1cc(Cl)ccc1OC.Cl
InChIKey: XQXLIZUFYLRIQF-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]-SCH23390 from recombinant human D5 receptor transiently expressed in HEKT cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 4227 nM (pChEMBL 5.369999885559082)
Descriptors: MW 468.04, ALogP 5.86, HBA 3, HBD 2, PSA 57.36, QED 0.33
Compound (SMILES): COc1ccc(C[C@H](NC(=O)[C@H](C)NC(=O)CN2CCOCC2)C(=O)N[C@@H](CCC2CCCCC2)C(=O)[C@@]2(C)CO2)cc1
InChIKey: XOVCQLITIBRPQB-ZBCYONBYSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S constitutive proteasome beta 5 chymotrypsin-like activity in human Raji cell lysates after 1 hr by competitive ABPP assay
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 600.76, ALogP 1.76, HBA 8, HBD 3, PSA 138.6, QED 0.26
Compound (SMILES): C[C@@]1(Cc2ccc(C#N)cc2)C(=O)N(c2cc(Cl)cc(Cl)c2)c2ncc(C(=O)NC3(c4nc(C5CCC5)no4)CC3)n21
InChIKey: VATLFUUMDRXLTK-GDLZYMKVSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: GPCRScan assay: inhibition of Sigma 2
Measurement: Ki = 557.65 nM (pChEMBL 6.25)
Descriptors: MW 602.48, ALogP 5.77, HBA 8, HBD 1, PSA 129.94, QED 0.28
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CN3CCN(CC3)CC(=O)Nc3ccc(cc3)C[C@@H](NC(=O)CCc3ccccc3)C(=O)N2)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: MQDLMPVZWKXFOG-NYZPMSFKSA-N
Target: Vitamin K-dependent protein C (SINGLE PROTEIN), Homo sapiens
UniProt: P04070
Assay: Inhibition of human activated Protein C using Mes-DArg-Pro-Arg-AMC as substrate by Dixon plot analysis
Measurement: Ki = 42018 nM (pChEMBL 4.380000114440918)
Descriptors: MW 771.92, ALogP 2.18, HBA 8, HBD 7, PSA 201.85, QED 0.1
Compound (SMILES): CC(=O)O.CNc1nc(Nc2cnc(C#N)c(O[C@@H]3CCCNC3)c2)ncc1-c1cnn(C)c1
InChIKey: GZTCTVFBVJLJOM-XFULWGLBSA-N
Target: Ribosomal protein S6 kinase beta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23443
Assay: Inhibition of p70S6K (unknown origin) using biotin-labelled STK substrate-1 as substrate incubated for 60 mins by HTRF assay
Measurement: IC50 = 625.68 nM (pChEMBL 6.199999809265137)
Descriptors: MW 405.47, ALogP 2.06, HBA 10, HBD 3, PSA 125.6, QED 0.56
Compound (SMILES): O=C(NO)c1ccc(Cn2c3c(c4ccccc42)CS(=O)(=O)CC3)cc1
InChIKey: JTWSNIOCMRULQH-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of human HDAC5 using fluorogenic HDAC substrate
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 370.43, ALogP 2.28, HBA 5, HBD 2, PSA 88.4, QED 0.55
Compound (SMILES): COc1nc(C#N)ccc1N[C@@H](C)c1cc2cc(Cl)ccc2[nH]c1=O
InChIKey: LXAVQRJBWNUBTP-JTQLQIEISA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of human Myc-DDK-tagged IDH1 R132H mutant assessed as reduction in NADPH consumption pre-incubated for 15 mins followed by alpha-ketoglutarate substrate and NADPH addition after 45 mins by diaphorase and resazurin dye based assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 354.8, ALogP 3.63, HBA 5, HBD 2, PSA 90.8, QED 0.75
Compound (SMILES): COc1nn(C)cc1Nc1ncc(Br)c(-c2c[nH]c3c(NC(=O)[C@@H](C)N4CCN(C)CC4)cccc23)n1
InChIKey: PCJQEPKPLJLWMX-OAHLLOKOSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: JAK Enzymatic Assay: Enzyme inhibition studies were performed using recombinant JAK1 (amino acids 866-1154, Life Technologies, #PV4774, Carlsbad, Calif.), JAK2 (amino acids 831-1132), or JAK3 (amino acids 781-1124) under buffer conditions of 50 mM HEPES pH 7.3, 1 mM DTT, 0.01% Tween® 20, 50 μg/mL BSA, and 10 mM MgCl2. JAK enzyme was expressed as an N-terminal GST fusion in insect cells and purified by glutathione-affinity and size-exclusion chromatographies. Enzymes were assayed both at their respective ATP Km (JAK1: 55 μM, JAK2: 15 μM, JAK3: 3 μM) and the approximated high end of physiological ATP concentration of 5 mM, in the presence of inhibitor dosed at 30, 3, 0.3, 0.03, 0.003 and 0 μM final test concentrations. For JAK1, 6 nM of enzyme (for Km ATP assay) or 4 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (FITC-C6-KKHTDDGYMPMSPGVA-NH2 (SEQ ID NO:1), Intonation, Boston, Mass.). For JAK2, 0.8 nM of enzyme (for Km ATP assay) or 0.3 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NH2 (SEQ ID NO:2), Intonation, Boston, Mass.). For JAK3, 0.2 nM of enzyme (for Km ATP assay) or 0.1 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NH2 (SEQ ID NO:2), Intonation, Boston, Mass.). Phosphorylated and unphosphorylated peptides were separated and quantified by a Caliper LC3000 system (Caliper Life Sciences, MA) for calculating percent inhibition. The results of this assay are shown in Table 16 and indicate that the compounds of Formula (I), (Ia), (Ib) and Table 1 exhibit preferential inhibition of JAK1 over JAK2 (in many cases demonstrating over 100 times selectivity for inhibition of JAK1 vs. JAK2).
Measurement: IC50 = 15400 nM (pChEMBL 4.809999942779541)
Descriptors: MW 568.48, ALogP 3.45, HBA 9, HBD 3, PSA 116.23, QED 0.31
Compound (SMILES): O=C(O)c1ccc(-n2cc(C(=O)c3c(Cl)cccc3C(F)(F)F)c3c(F)cccc32)c(F)c1
InChIKey: RXFPAAYTOMUIII-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated for 5 mins followed by NADPH addition measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 479.79, ALogP 6.51, HBA 3, HBD 1, PSA 59.3, QED 0.27
Compound (SMILES): O=C(Nc1ccccc1)N1CCC(C(O)CC2c3ccccc3-c3cncn32)CC1
InChIKey: YQNFLDBZFLCLLR-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 = 93000 nM (pChEMBL 4.03000020980835)
Descriptors: MW 402.5, ALogP 4.15, HBA 4, HBD 2, PSA 70.39, QED 0.69
Compound (SMILES): O=C(O)c1ccc(CNc2ccc(-c3ccc(-c4nc5cc(Cl)ccc5[nH]4)cn3)cn2)cc1
InChIKey: KMRKVWIQPVPEED-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 455.91, ALogP 5.65, HBA 5, HBD 3, PSA 103.79, QED 0.31
Compound (SMILES): CN1CCc2c(nnn2CC(=O)Nc2ccc(Cl)c(S(=O)(=O)N3CC[C@H](C4CC4)C3)c2)C1
InChIKey: DBLNLPCEKQBLAI-HNNXBMFYSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Binding affinity to human partial length CECR2 (P423 to D543 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 479.01, ALogP 1.98, HBA 7, HBD 1, PSA 100.43, QED 0.68
Compound (SMILES): Cc1sc2c(c1C)C(c1ccc(Cl)cc1)=N[C@@H](CC(=O)NCCOCCOCCN)c1nnc(C)n1-2
InChIKey: WTJMHBMWPMTETL-FQEVSTJZSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 in human H1229 cells transfected with HPV-E2 assessed as transrepression of HPV-long control region by luciferase reporter assay
Measurement: EC50 = 8490 nM (pChEMBL 5.070000171661377)
Descriptors: MW 531.08, ALogP 3.3, HBA 9, HBD 2, PSA 116.65, QED 0.37
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc3c(F)c4oc5ccc(-c6cnc([C@@H]7CCCN7C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]6)cc5c(=O)c4cc3c2)[nH]1)C(C)C
InChIKey: LYOZUKZKCWAPEP-SEXBWERRSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 2b assessed as decrease in viral replication
Measurement: EC50 > 100 nM (pChEMBL 7)
Descriptors: MW 848.93, ALogP 7.11, HBA 10, HBD 4, PSA 204.85, QED 0.1
Compound (SMILES): Cc1noc(-c2ccc3nc(Nc4cc([C@H](C)N5CCN(C(=O)CC(F)(F)F)CC5)ccn4)[nH]c3c2)n1
InChIKey: SYMILEXMAHCATG-AWEZNQCLSA-N
Target: IKK epsilon/TBK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UHD2
Assay: Inhibition of IKKepsilon/TBK1 in human MDB-MB-231 cells transduced with lentiviral vector expressing human IRF3 assessed as decrease in poly(I:C)-stimulated IRF3 phosphorylation at S385/386 residues preincubated for 1 hr followed by poly(I:C) addition and measured after 1 hr
Measurement: IC50 = 3020 nM (pChEMBL 5.519999980926514)
Descriptors: MW 514.51, ALogP 4.22, HBA 8, HBD 2, PSA 116.07, QED 0.39
Compound (SMILES): COc1nn(C)cc1Nc1nccc(-c2c[nH]c3c(NC(=O)[C@@H](C)N4CCN(C)CC4)cccc23)n1
InChIKey: CVCVOSPZEVINRM-MRXNPFEDSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: JAK Enzymatic Assay: Enzyme inhibition studies were performed using recombinant JAK1 (amino acids 866-1154, Life Technologies, #PV4774, Carlsbad, Calif.), JAK2 (amino acids 831-1132), or JAK3 (amino acids 781-1124) under buffer conditions of 50 mM HEPES pH 7.3, 1 mM DTT, 0.01% Tween® 20, 50 μg/mL BSA, and 10 mM MgCl2. JAK enzyme was expressed as an N-terminal GST fusion in insect cells and purified by glutathione-affinity and size-exclusion chromatographies. Enzymes were assayed both at their respective ATP Km (JAK1: 55 μM, JAK2: 15 μM, JAK3: 3 μM) and the approximated high end of physiological ATP concentration of 5 mM, in the presence of inhibitor dosed at 30, 3, 0.3, 0.03, 0.003 and 0 μM final test concentrations. For JAK1, 6 nM of enzyme (for Km ATP assay) or 4 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (FITC-C6-KKHTDDGYMPMSPGVA-NH2 (SEQ ID NO:1), Intonation, Boston, Mass.). For JAK2, 0.8 nM of enzyme (for Km ATP assay) or 0.3 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NH2 (SEQ ID NO:2), Intonation, Boston, Mass.). For JAK3, 0.2 nM of enzyme (for Km ATP assay) or 0.1 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NH2 (SEQ ID NO:2), Intonation, Boston, Mass.). Phosphorylated and unphosphorylated peptides were separated and quantified by a Caliper LC3000 system (Caliper Life Sciences, MA) for calculating percent inhibition. The results of this assay are shown in Table 16 and indicate that the compounds of Formula (I), (Ia), (Ib) and Table 1 exhibit preferential inhibition of JAK1 over JAK2 (in many cases demonstrating over 100 times selectivity for inhibition of JAK1 vs. JAK2).
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 489.58, ALogP 2.69, HBA 9, HBD 3, PSA 116.23, QED 0.36
Compound (SMILES): C#CCOc1cnc(C(=O)Nc2cc(F)c(F)c([C@@]3(C)N=C(N)S[C@@]4(C(F)F)C[C@@H]34)c2)cn1
InChIKey: NURKHPHCXJUBHN-DLPLYFIVSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of recombinant human BACE2 expressed in HEK293 cells co-transfected with N-terminal HA-tagged/C-terminal Myc tagged Mbeta chain of human PMEL17 measured after overnight incubation by Gaussia luciferase reporter gene assay
Measurement: IC50 = 1290 nM (pChEMBL 5.889999866485596)
Descriptors: MW 479.46, ALogP 3.32, HBA 7, HBD 2, PSA 102.49, QED 0.49
Compound (SMILES): Nc1nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(O)O[C@H]4[C@@H](F)[C@H](n5cnc6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3O)c(=O)[nH]1
InChIKey: VSWSFOHKUMIXAS-XBNNLADJSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Activation of recombinant human STING haplotype R293Q mutant expressed in 293T cells measured after 30 mins in presence of digitonin A by bright Glo-luciferase reporter gene assay
Measurement: EC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 676.41, ALogP -1.36, HBA 19, HBD 6, PSA 309.42, QED 0.13
Compound (SMILES): CCCCCn1c(=O)n(CCCCN2CCN(c3ccc(F)cc3)CC2)c2ccccc21
InChIKey: CYNRAFPHCBCEFW-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]paroxetine from serotonin transporter in rat brainstem membranes after 120 mins by radioligand binding assay
Measurement: Ki = 446 nM (pChEMBL 6.349999904632568)
Descriptors: MW 438.59, ALogP 4.73, HBA 5, HBD 0, PSA 33.41, QED 0.43
Compound (SMILES): CCNC(=O)Nc1ccc(-c2nc(N3CCOC[C@@H]3C)c3c(n2)C(C)(C)S(=O)(=O)C3)cc1
InChIKey: IZLPVLBNRGPOHA-AWEZNQCLSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Binding affinity to mTOR in mixed human HeLa/Jurkat/K562 cell lysate by LC-MS based chemoproteomic assay
Measurement: Kd = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 459.57, ALogP 2.67, HBA 7, HBD 2, PSA 113.52, QED 0.72
Compound (SMILES): COC(=O)c1ccc(CSc2ccc3nc(N)sc3c2)cc1
InChIKey: CJRBTBVFIXNQRL-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of human CYP2C19 expressed in baculovirus infected insect cells using beetle D-luciferin as substrate preincubated for 30 mins followed by NADPH addition and measured after 30 mins by CYP450-Glo assay
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 330.43, ALogP 3.96, HBA 6, HBD 1, PSA 65.21, QED 0.58
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@@H](N)[C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N1)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)O)C(C)C)[C@@H](C)O
InChIKey: JHGVKJZRAQPJTO-JHKJEGEHSA-N
Target: Neuronal acetylcholine receptor; alpha2/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12390
Assay: Antagonist activity at rat alpha2beta2 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced response at -70 mV holding potential by two electrode voltage-clamp assay
Measurement: IC50 = 2990 nM (pChEMBL 5.519999980926514)
Descriptors: MW 3390.84
Compound (SMILES): Nc1n[nH]c(N2CCC(N(CCO)CCc3ccc(Cl)cc3)CC2)n1
InChIKey: WJUJBVLSGCCBRG-UHFFFAOYSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Inhibition of full-length 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 after 60 mins by fluorometric assay
Measurement: IC50 = 111 nM (pChEMBL 6.960000038146973)
Descriptors: MW 364.88, ALogP 1.55, HBA 6, HBD 3, PSA 94.3, QED 0.69
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)Cc4ccc(Cl)c(C(F)(F)F)c4)cc3)c2cc1OC
InChIKey: YOHLRCOPRAVUCJ-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of recombinant human GST-tagged PDGFRA cytoplasmic domain (550 to 1089 residues) expressed in baculovirus expression system by Z-lyte assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 516.9, ALogP 6.9, HBA 5, HBD 1, PSA 69.68, QED 0.29
Compound (SMILES): CC(C)(C)OC(=O)N1CCN(Cc2ccc3nc4n(c(=O)c3c2)-c2ccc(F)cc2C4=O)CC1
InChIKey: JPWWUFBCQPTXFF-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6ZQW0
Assay: Inhibition of human IDO2 transfected in human U87MG cells assessed as reduction in kynurenine production using L-tryptophan as substrate incubated with for 6 hrs
Measurement: IC50 = 8050 nM (pChEMBL 5.090000152587891)
Descriptors: MW 464.5, ALogP 3.12, HBA 7, HBD 0, PSA 84.74, QED 0.45
Compound (SMILES): Nc1ncc(C(=O)NC2CCC(=Cc3cccc(Oc4ccc(C(F)(F)F)cn4)c3)CC2)cn1
InChIKey: RNWIDHFRJFXZOI-GDNBJRDFSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: FAAH Assay: All reagents were purchased from Sigma-Aldrich unless specified. Human and Rat Fatty Acid Amide Hydrolase (FAAH) genes used in assay have been described by Patricelli et al. (Biochemistry. 1998, 37(43), 15177-87). The transmembrane domain-deleted Fatty Acid Amide Hydrolase (FAAH) genes were cloned into pET15b (Novagen, #69661) (human FAAH)/pET 28a (Novagen, #69864-3) (rat FAAH gene) plasmids and expressed in E coli BL21 DE3. Chaperone protein groEL-groES in pGRO7 plasmid (Takara Bio Inc, Japan) was co-expressed with Fatty Acid Amide Hydrolase (FAAH) to improve solubility of the protein expressed in E coli. The protein was expressed and enriched as described in Mileni et al. (Proc Natl Acad Sci USA. 2008, 105(35),12820-4). Briefly, the bacterial cultures in Luria Broth (2 L) were induced with arabinose (2 mM) and Isopropyl (β-D-1-thiogalactopyranoside, IPTG (1 mM), for 20 h at room temperature. The cultures were centrifuged at 1200×g for 10 min and the cell pellet was resuspended in 100 mL buffer containing of 20 mM NaPi (pH 7.4), 100 mM NaCl, Benzonase (500u), Aprotinin (1 μg/mL) and Leupeptin (1 μg/mL). Cells were lyzed by sonication (Amp 20%, Pulse 15 s×15, on ice) and the cell debris removed by centrifugation at 5000×g for 20 min. The supernatant was enriched via ultracentrifugation at 100,000×g for 1 h and the cell pellet was resuspended in 16 mL buffer containing 20 mM NaPi (pH 7.8), 500 mM NaCl, 1% Triton X-100. The resuspended cell extract was subjected to ultra-centrifugation at 100,000×g for 1 h and the enriched supernatant was used in the in vitro assay. All protein extraction steps were carried out on ice or at 4° C.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 469.47, ALogP 5.02, HBA 6, HBD 2, PSA 103.02, QED 0.54
Compound (SMILES): O=C(O)CNC(=O)c1c(O)c2c(n(Cc3ccc(C(F)(F)F)cc3)c1=O)COC2
InChIKey: YAXLMMDYZWFFAQ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of iKr (unknown origin)
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 412.32, ALogP 1.47, HBA 6, HBD 3, PSA 117.86, QED 0.68
Compound (SMILES): CCNC1=N[C@@H]2[C@@H](O)[C@H](OC)[C@@H](CO)O[C@@H]2S1
InChIKey: ZHRPYFJVBTZRKC-JGKVKWKGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 262.33, ALogP -0.84, HBA 7, HBD 3, PSA 83.31, QED 0.62
Compound (SMILES): Cc1cc(N2CC(C(=O)NNC(=S)Nc3ccccc3)CC2=O)cc(C)c1S(N)(=O)=O
InChIKey: OWIMCWHOYBJYPJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to recombinant human CA7 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 6500 nM (pChEMBL 5.190000057220459)
Descriptors: MW 461.57, ALogP 1.32, HBA 5, HBD 4, PSA 133.63, QED 0.4
Compound (SMILES): O=C1NC(=O)C2(CCCc3ccccc32)N1S(=O)(=O)c1ccc(Br)cc1
InChIKey: PLHRUKZORBTXRB-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P07943
Assay: Inhibition of ALR2 in rat lens assessed as reduction in sorbitol accumulation incubated for 3 hrs in presence of 28 mM glucose by gas chromatographic analysis relative to control
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 435.3, ALogP 2.92, HBA 4, HBD 1, PSA 83.55, QED 0.74
Compound (SMILES): O=C(COc1ccc(-c2nc3ccccc3c(=O)[nH]2)cc1)Nc1cccc(Cl)c1
InChIKey: MDHSFSUMZBWHRU-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK6/cyclin D1 (unknown origin) using RBER-CHKtide as substrate measured after 1 hr by ADP-glo luminescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 405.84, ALogP 4.26, HBA 4, HBD 2, PSA 84.08, QED 0.52
Compound (SMILES): CC(=O)c1c(NS(C)(=O)=O)c2cc(-c3ccc(Cl)cc3)c(-c3ccc(Cl)cc3Cl)nc2n(C)c1=O
InChIKey: HSEQWGUPLOFKEC-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000316b OPRD1
Measurement: Ki = 1415 nM (pChEMBL 5.849999904632568)
Descriptors: MW 550.85, ALogP 5.8, HBA 6, HBD 1, PSA 98.13, QED 0.32
Compound (SMILES): O=C(NO)c1ccc(Cn2cc(CN3CCCC3)c3ccccc32)cc1
InChIKey: MMKIXMJBZVVFRQ-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant full-length C-terminal His-tagged human HDAC2 expressed in baculovirus infected Sf9 insect cells measured after 40 mins by HDAC-Glo1/2 luminescent assay
Measurement: IC50 = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 349.43, ALogP 3.4, HBA 4, HBD 2, PSA 57.5, QED 0.55
Compound (SMILES): Cl.NOC(c1ccccc1)c1ccc(Cl)cc1Cl
InChIKey: NJJSJNMGOHDNGX-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO expressed in human T-REx cells using L-tryptophan as substrate after 20 hrs
Measurement: IC50 = 4820 nM (pChEMBL 5.320000171661377)
Descriptors: MW 268.14, ALogP 3.97, HBA 2, HBD 1, PSA 35.25, QED 0.85
Compound (SMILES): O=C1c2cc(F)ccc2-n2c1nc1ccc(N3CCCCC3)cc1c2=O
InChIKey: DCMJYRYVAMKYLN-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6ZQW0
Assay: Inhibition of human IDO2 transfected in human U87MG cells assessed as reduction in kynurenine production using L-tryptophan as substrate incubated with for 6 hrs
Measurement: IC50 = 22220 nM (pChEMBL 4.650000095367432)
Descriptors: MW 349.37, ALogP 3.06, HBA 5, HBD 0, PSA 55.2, QED 0.53
Compound (SMILES): CCN(CCCSc1nnc(-c2ccccc2)n1C)CC1CC1c1cc(Cl)ccc1OC.Cl
InChIKey: UAFZANNHBIFIBH-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]-SCH23390 from recombinant human D5 receptor transiently expressed in HEKT cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 471.07, ALogP 5.75, HBA 6, HBD 0, PSA 43.18, QED 0.26
Compound (SMILES): Cc1ccc2c(c1)C1=NCCN1C(=S)S2
InChIKey: NOYKRSRQTIQQCU-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant human full length N-terminal GST-tagged HDAC5 expressed in baculovirus infected Sf9 cells using Boc-Lys(TFA)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 234.35, ALogP 2.45, HBA 3, HBD 0, PSA 15.6, QED 0.64
Compound (SMILES): O=C(O)c1ccc(-n2cc(C(=O)c3c(Cl)cccc3Cl)c3cccc(F)c32)cc1
InChIKey: IUHZJIRXCFINGV-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate preincubated for 5 mins followed by NADPH addition measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 = 11100 nM (pChEMBL 4.960000038146973)
Descriptors: MW 428.25, ALogP 6.01, HBA 3, HBD 1, PSA 59.3, QED 0.41
Compound (SMILES): N#CCOc1ccc(-c2cn3c(=O)n(-c4ccccc4)nc3c(N)n2)cc1
InChIKey: WWQYFWNNAFDIPN-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Antagonist activity at human adenosine A2A receptor expressed in CHO cells assessed as inhibition of NECA-stimulated adenylyl cyclase activity by Glo-sensor cAMP assay
Measurement: IC50 = 157 nM (pChEMBL 6.800000190734863)
Descriptors: MW 358.36, ALogP 2.03, HBA 8, HBD 1, PSA 111.23, QED 0.6
Compound (SMILES): CC[C@H](Nc1ccc(S(=O)(=O)Nc2nccs2)cc1)c1ccccc1
InChIKey: IZFPWSRDXPTRBZ-KRWDZBQOSA-N
Target: Sodium channel protein type 1 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35498
Assay: Sodium Influx Assay (In Vitro Assay): This sodium influx assay employs the use of the cell permeable, sodium sensitive dye ANG2 to quantify sodium ion influx through sodium channels which are maintained in an open state by use of sodium channel modulators. This high throughput sodium influx assay allows for rapid profiling and characterization of sodium channel blockers.In general, Trex HEK293 cells were stably transfected with an inducible expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit and with an expression vector containing full length cDNA coding for the β1-subunit. Sodium channel expressing cell lines were induced with tetracycline (1 μg/mL) and plated on 384-well PDL-coated plates at a density of 25K-30K cells/well in culture media (DMEM, containing 10% FBS and 1% L-glutamine). After overnight incubation (37° C., 5% CO2), culture media was removed and cells were loaded with 5 uM ANG2 dye for 1-1.5 h in Buffer 1 (155 mM NMDG, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 10 mM glucose, adjusted with Tris to pH 7.4). Access dye was removed and cells were incubated with test compounds for 1 hr in buffer 1 containing sodium channel modulator(s) at room temperature. Hamamatsu FDSS μCell was used to perform a 1:1 addition of Na/K challenge buffer (140 mM NaCl, 20 mM HEPES, 1 mM CaCl2, 15 mM KCl, 1 mM MgCl2, 10 mM glucose, adjusted with Tris to pH 7.4) and simultaneously read plates at excitation wavelength of 530 nm and emission wavelength set at 558 nm. Percent inhibition of sodium ion influx was calculated for each test compound at each test concentration to determine the IC50 values.
Measurement: IC50 = 2413 nM (pChEMBL 5.619999885559082)
Descriptors: MW 373.5, ALogP 4.51, HBA 5, HBD 2, PSA 71.09, QED 0.64
Compound (SMILES): COc1cc2c(cc1OC)[C@H](c1ccc(F)cc1)N(C(=O)N1CCc3cc(OC)c(OC)cc3[C@@H]1c1ccc(F)cc1)CC2
InChIKey: BHCFMOBCNHFBGR-HEVIKAOCSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9ERZ8
Assay: Antagonist activity at recombinant rat TRPV4 expressed in HEK293 cells assessed as inhibition of 4alphaPDD-induced intracellular calcium accumulation preincubated for 5 mins followed by 4alphaPDD addition by Fluo-4-AM probe-based spectrofluorimetric assay
Measurement: IC50 = 96200 nM (pChEMBL 4.019999980926514)
Descriptors: MW 600.66, ALogP 6.71, HBA 5, HBD 0, PSA 60.47, QED 0.25
Compound (SMILES): CCCCNC(=O)c1cc(S(N)(=O)=O)c(Br)cc1S(=O)(=O)c1ccccc1
InChIKey: FATAPRQFXGZRGG-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Binding affinity to recombinant human carbonic anhydrase 5b expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 475.39, ALogP 2.46, HBA 5, HBD 2, PSA 123.4, QED 0.6
Compound (SMILES): COC[C@H]1C[C@@H](c2nc3ccc4cc5c(cc4c3[nH]2)OCc2cc(-c3cnc([C@@H]4C[C@H](C)CN4C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]3)ccc2-5)N(C(=O)[C@@H](NC(=O)OC)C(C)C)C1
InChIKey: QRKFUUOTBBROJV-SORRNWNHSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 4a ED43 infected in human HuH7 transient chimeric replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.022 nM (pChEMBL 10.65999984741211)
Descriptors: MW 849, ALogP 6.87, HBA 10, HBD 4, PSA 193.1, QED 0.11
Compound (SMILES): OC(CC1c2c(F)cccc2-c2cncn21)C1CCC(F)(F)CC1
InChIKey: FPKRCRNJVIHTNG-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 336.36, ALogP 4.17, HBA 3, HBD 1, PSA 38.05, QED 0.91
Compound (SMILES): CC(C)(C)c1ccc(CN2CCN(S(=O)(=O)Nc3ccc(SCCc4ccccc4)cc3C(=O)O)CC2)cc1
InChIKey: WIWNZUYJVZDDEH-UHFFFAOYSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Inhibition of N-terminal His6-tagged human Bcl-2 isoform 2 (1 to 34 residues and 92 to 202 residues with Bcl-xL sequence (35 to 50 residues) expressed in Escherichia coli Rosetta2 DE3 by fluorescent labeled FAM-Bid peptide based fluorescence polarization assay
Measurement: Ki > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 567.78, ALogP 5.49, HBA 5, HBD 2, PSA 89.95, QED 0.32
Compound (SMILES): OCc1cccc(-c2ccc3nc(-c4ccc(Cl)cc4)cn3c2)c1
InChIKey: IHUPABWARJLUMA-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 4 group A member 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q06219
Assay: Agonist activity at Nurr1 in mouse N2A cells harboring NBRE by luciferase reporter gene assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 334.81, ALogP 4.81, HBA 3, HBD 1, PSA 37.53, QED 0.58
Compound (SMILES): COC1Cc2ccccc2[C@]2(CC[C@@H](N(C)CC3CCCCC3)CC2)O1
InChIKey: MBRMOGQHSBUGKH-FXCIWXGGSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]U69,593 from kappa opioid receptor in guinea pig brain membrane after 120 mins by scintillation counting analysis
Measurement: Ki = 980 nM (pChEMBL 6.010000228881836)
Descriptors: MW 357.54, ALogP 4.88, HBA 3, HBD 0, PSA 21.7, QED 0.77
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: VAGFPILJLLZTKR-ISSCZAFUSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled human calcitonin from human calcitonin receptor expressed in BHK tkts13 whole cells incubated for 60 mins by scintillation proximity assay
Measurement: IC50 = 0.628 nM (pChEMBL 9.199999809265137)
Descriptors: MW 3736.23
Compound (SMILES): CCCCCn1/c(=N/C(=O)c2ccc(C(F)(F)F)cc2)sc2ccccc21
InChIKey: ZKQOBFAUDJCQMQ-CLCOLTQESA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Antagonist activity at N-terminal Flag epitope tagged CB1 (unknown origin) expressed in HTLA cells assessed as decrease in CP55940-induced beta-arrestin recruitment pretreated with non-selective cannabinoid receptor agonist CP55940 for 30 mins and measured after 20 mins by Tango assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 392.45, ALogP 5.65, HBA 3, HBD 0, PSA 34.36, QED 0.52
Compound (SMILES): O=C(O)c1ccc(-n2cc(C(=O)c3c(Cl)cccc3C(F)(F)F)c3c(F)cccc32)cc1
InChIKey: CWHKOHWOAVTDCW-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 5 mins followed by NADPH addition measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 = 16400 nM (pChEMBL 4.789999961853027)
Descriptors: MW 461.8, ALogP 6.37, HBA 3, HBD 1, PSA 59.3, QED 0.28
Compound (SMILES): CO[C@H](CN1CC[C@@]2(C)c3cc(O)ccc3C[C@@H]1[C@@H]2C)c1ccccc1
InChIKey: CYJVECUASMVXNS-RAKGIWIYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at Rluc-tagged DOR receptor (unknown origin) expressed in human SH-5YSY cells co-expressing RGFP-fused to Gbeta1 assessed as increase in DOR/G beta1 protein interaction incubated for 5 mins in presence of coelenterazine by BRET assay
Measurement: EC50 = 32.36 nM (pChEMBL 7.489999771118164)
Descriptors: MW 351.49, ALogP 4.3, HBA 3, HBD 1, PSA 32.7, QED 0.89
Compound (SMILES): COc1ccc(NC(=O)c2cccc(-c3nc(NC(P(=O)(O)O)P(=O)(O)O)c4ccsc4n3)c2)cc1F
InChIKey: XPPGEOUCUMGOGK-UHFFFAOYSA-N
Target: Geranylgeranyl pyrophosphate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O95749
Assay: In Vitro hGGPPS Inhibition Assay: The assay was based on a literature procedure (Kavanagh, et al. J. Biol. Chem., 2006, 281, 22004-22012) with minor modifications. All assays were run in triplicate using recombinant human GGPPS (80 ng), FPP (10 μM), IPP (8.3 μM; 3H-IPP, 40 mCi/mmoL) in a final volume of 100 μL buffer containing 50 mM Tris pH 7.7, 2 mM MgCl2, 1 mM TCEP, 5 μg/mL BSA and 0.2% (w/v) Tween 20. The enzyme and test compound were pre-incubated in the assay buffer in a volume of 80 μL at 37° C. for 10 mins. Afterwards, the substrates (FPP, IPP) were added to start the reaction, which also bring the compound, substrate, and buffer contents to the desired final concentrations as indicated above. The assay mixture was then incubated at 37° C. for 15 mins (Note: the incubation time is based from the curve determined each time a new batch of enzyme is produced). Assays were terminated by the addition of 200 μL of HCl/MeOH (1:4) and incubated for 10 min at 37° C. The mixture was then extracted with 700 μL of petroleum ether, dried through a plug of anhydrous Mg2SO4 and 300 μL of the dried ligroin phase was combined with 8 mL of scintillation cocktail. Finally, the radioactivity was counted using a Beckman Coulter LS6500 liquid scintillation counter.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 568.42, ALogP 3.81, HBA 8, HBD 6, PSA 191.2, QED 0.17
Compound (SMILES): Cc1cc(S(N)(=O)=O)c(C)cc1N1CC(C(=O)O)CC1=O
InChIKey: MTHLUECOFDPPBS-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Binding affinity to recombinant human CA7 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 312.35, ALogP 0.39, HBA 4, HBD 2, PSA 117.77, QED 0.84
Compound (SMILES): O=C(/C=C/c1cccn(CCc2ccc3ccccc3c2)c1=O)NO
InChIKey: XQXZIMLBLPDARP-MDZDMXLPSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant full-length human HDAC5 using Boc-Lys(trifluoroacetyl)-AMC as substrate measured after 2 hrs by fluorescence assay
Measurement: IC50 = 38540.65 nM (pChEMBL 4.409999847412109)
Descriptors: MW 334.38, ALogP 2.76, HBA 4, HBD 2, PSA 71.33, QED 0.43
Compound (SMILES): CC(=O)C1=C(O)C(=O)N(c2ccc(Br)cc2F)C1C1CCCCC1
InChIKey: ARZUMHIABDHPTN-UHFFFAOYSA-N
Target: C-C chemokine receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32246
Assay: Antagonist activity at human TEV protease site linked CCR1 expressed in human U20S cell membranes co-expressing Gal4-VP16 transcription factor assessed as reduction in CCL3-induced G-protein activation preincubated for 30 mins in presence of CCL3 followed by incubation of 90 mins by [35S]GTPgammaS binding assay
Measurement: IC50 = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 396.26, ALogP 4.28, HBA 3, HBD 1, PSA 57.61, QED 0.83
Compound (SMILES): CCCN(CCCCNC(=O)c1cc2ccccc2[nH]1)CC1CC1c1cc(Cl)ccc1OC.Cl
InChIKey: XQXLIZUFYLRIQF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-Mesulergine from recombinant human 5HT2C receptor expressed in HEKT cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 85.1 nM (pChEMBL 7.070000171661377)
Descriptors: MW 468.04, ALogP 5.86, HBA 3, HBD 2, PSA 57.36, QED 0.33
Compound (SMILES): COc1ccc(C[C@H](NC(=O)[C@H](C)NC(=O)CN2CCOCC2)C(=O)N[C@@H](CCC2CCCCC2)C(=O)[C@@]2(C)CO2)cc1
InChIKey: XOVCQLITIBRPQB-ZBCYONBYSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of 20S immunoproteasome beta 5 in human Raji cell lysates after 1 hr by competitive ABPP assay
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 600.76, ALogP 1.76, HBA 8, HBD 3, PSA 138.6, QED 0.26
Compound (SMILES): C[C@@]1(Cc2ccc(C#N)cc2)C(=O)N(c2cc(Cl)cc(Cl)c2)c2ncc(C(=O)NC3(c4nc(C5CCC5)no4)CC3)n21
InChIKey: VATLFUUMDRXLTK-GDLZYMKVSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: GPCRScan assay: inhibition of Sigma 2
Measurement: Ki = 506.99 nM (pChEMBL 6.289999961853027)
Descriptors: MW 602.48, ALogP 5.77, HBA 8, HBD 1, PSA 129.94, QED 0.28
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CN3CCN(CC3)CC(=O)Nc3ccc(cc3)C[C@@H](NC(=O)CCc3ccccc3)C(=O)N2)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: MQDLMPVZWKXFOG-NYZPMSFKSA-N
Target: Trypsin (SINGLE PROTEIN), Sus scrofa
UniProt: P00761
Assay: Inhibition of porcine trypsin using Mes-DArg-Gly-Arg-AMC as substrate by Dixon plot analysis
Measurement: Ki = 1429 nM (pChEMBL 5.840000152587891)
Descriptors: MW 771.92, ALogP 2.18, HBA 8, HBD 7, PSA 201.85, QED 0.1
Compound (SMILES): CC(=O)O.CNc1nc(Nc2cnc(C#N)c(O[C@@H]3CCCNC3)c2)ncc1-c1cnn(C)c1
InChIKey: GZTCTVFBVJLJOM-XFULWGLBSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2 (unknown origin) using biotin-labelled STK substrate-1 as substrate incubated for 60 mins by HTRF assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 405.47, ALogP 2.06, HBA 10, HBD 3, PSA 125.6, QED 0.56
Compound (SMILES): O=C(NO)c1ccc(Cn2c3c(c4ccccc42)CS(=O)(=O)CC3)cc1
InChIKey: JTWSNIOCMRULQH-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human HDAC6 using fluorogenic HDAC substrate
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 370.43, ALogP 2.28, HBA 5, HBD 2, PSA 88.4, QED 0.55