lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@](O)(Cn1cc(C#N)c(Br)n1)C(=O)Nc1ccc(C#N)c(C(F)(F)F)c1
InChIKey: OCXFZMGTMBVOSH-HNNXBMFYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Affinity Assay: hAR-LBD (633-919) was cloned into pGex4t.1. Large scale GST-tagged AR-LBD was prepared and purified using a GST column. Recombinant AR-LBD was combined with [3H]mibolerone (PerkinElmer, Waltham, Mass.) in buffer A (10 mM Tris, pH 7.4, 1.5 mM disodium EDTA, 0.25 M sucrose, 10 mM sodium molybdate, 1 mM PMSF) to determine the equilibrium dissociation constant (Kd) of [3H]mibolerone. Protein was incubated with increasing concentrations of [3H]mibolerone with and without a high concentration of unlabeled mibolerone at 4° C. for 18 h in order to determine total and non-specific binding. Non-specific binding was then subtracted from total binding to determine specific binding and non-linear regression for the ligand binding curve with one site saturation was used to determine the Kd of mibolerone. The results of this assay are reported as Ki values (nM) in Table 1 in the column labeled wt AR Binding (Ki(left)). As discussed above and is apparent from Table 1, there is a poor correlation between AR-LBD affinity and SARD activity. E.g., see in vitro SARD activity for 1002, 1005, 1015, 1019, 1020, and 1022 despite no binding affinity for the LBD.
Measurement: Ki = 202 nM (pChEMBL 6.699999809265137)
Descriptors: MW 442.19, ALogP 2.8, HBA 6, HBD 2, PSA 114.73, QED 0.76
Compound (SMILES): O=C(Nc1ccc(N2CCOCC2)cc1N1CCOCC1)c1cnn(-c2ccccc2)n1
InChIKey: FIGVRMOGMRMIGE-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of human TRKB by FLIPR assay
Measurement: IC50 = 15900 nM (pChEMBL 4.800000190734863)
Descriptors: MW 434.5, ALogP 2.19, HBA 8, HBD 1, PSA 84.75, QED 0.66
Compound (SMILES): N#C[C@@H]1CC(F)(F)CN1C(=O)CNC(=O)c1csc(-c2ccc(C(F)(F)F)cc2)n1
InChIKey: DSQKCKUPGCXGHL-LBPRGKRZSA-N
Target: Prolyl endopeptidase (SINGLE PROTEIN), Homo sapiens
UniProt: P48147
Assay: Inhibition of PREP (unknown origin) using AMC substrate by fluorometric assay
Measurement: IC50 = 1377 nM (pChEMBL 5.860000133514404)
Descriptors: MW 444.39, ALogP 3.32, HBA 5, HBD 1, PSA 86.09, QED 0.73
Compound (SMILES): CCCNNC(=O)c1ccc(CNC(=O)c2ccccc2)cc1
InChIKey: HATRHHNUHBOWCI-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Allosteric inhibition of C-terminal His-tagged recombinant human HDAC3 expressed in Sf9 cells pre-incubated for 2 hrs before acetylated lysine-aminomethyl coumarin-BOC addition and measured after 2 hrs by fluorescence based assay
Measurement: IC50 = 3.47 nM (pChEMBL 8.460000038146973)
Descriptors: MW 311.39, ALogP 2.26, HBA 3, HBD 3, PSA 70.23, QED 0.54
Compound (SMILES): CC(C)C(=O)Nc1cncc(-c2ccc3[nH]nc(-c4cc5c(N6CCN(C)CC6)nccc5[nH]4)c3c2)c1
InChIKey: QUHXPUVQLFTSTI-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 569 nM (pChEMBL 6.25)
Descriptors: MW 494.6, ALogP 4.51, HBA 6, HBD 3, PSA 105.83, QED 0.33
Compound (SMILES): CC(C)n1cnnc1-c1cccc(NC(=O)Nc2cc3ccccn3n2)n1
InChIKey: CBBBVHQOAFZUBJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: O43318
Assay: Inhibition of TAK1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 362.4, ALogP 3.21, HBA 7, HBD 2, PSA 102.03, QED 0.58
Compound (SMILES): CN(C)Cc1cncc(-c2cnc3[nH]nc(-c4nc5c(-c6cccc(F)c6)cncc5[nH]4)c3c2)c1
InChIKey: YBBUGSYNPXTSGW-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 464.51, ALogP 4.83, HBA 6, HBD 2, PSA 99.27, QED 0.38
Compound (SMILES): Cn1ccc2c(-c3nc4c(-n5cc(N[C@@H]6CCOC[C@@H]6N)cn5)ccnc4[nH]3)cccc21
InChIKey: MXZJNQSPLXUEQL-ZWKOTPCHSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK (unknown origin)
Measurement: IC50 = 0.21 nM (pChEMBL 9.680000305175781)
Descriptors: MW 428.5, ALogP 2.83, HBA 8, HBD 3, PSA 111.6, QED 0.41
Compound (SMILES): CCN(CC)C(=O)Oc1ccc(/C=C/C(=O)N2CCN(Cc3ccccc3)CC2)cc1OC
InChIKey: LUVGFBXWMIIQJF-WYMLVPIESA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 10600 nM (pChEMBL 4.96999979019165)
Descriptors: MW 451.57, ALogP 3.89, HBA 5, HBD 0, PSA 62.32, QED 0.57
Compound (SMILES): CCN1CC(CC#N)(n2cc(-c3nc(-c4cnn(C)c4)cn4nccc34)cn2)C1
InChIKey: LSEHWUWQKGKULM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human GST-tagged JAK2 catalytic domain (809 to 1153+9 residues) expressed in baculovirus expression system using FITC-KGGEEEEYFELVKK as substrate in presence of ATP at Km by microfluidic assay
Measurement: IC50 = 346 nM (pChEMBL 6.460000038146973)
Descriptors: MW 387.45, ALogP 1.94, HBA 9, HBD 0, PSA 92.86, QED 0.52
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCNc2ccccn2)CC1
InChIKey: RPOKNYKEZIGQTQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human recombinant 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in ERK1/2 phosphorylation levels incubated for 15 mins by Alphalisa assay
Measurement: EC50 = 17.38 nM (pChEMBL 7.760000228881836)
Descriptors: MW 408.88, ALogP 3.52, HBA 4, HBD 2, PSA 57.26, QED 0.69
Compound (SMILES): CCOC(=O)C(Nc1nc2nn(C)cc2c2nc(-c3ccco3)nn12)c1ccccc1
InChIKey: YWPXUUWVCDDDOD-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]-NECA from human A2A receptor expressed in CHO cell membrane by radioligand binding assay
Measurement: Ki = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 417.43, ALogP 2.99, HBA 10, HBD 1, PSA 112.37, QED 0.42
Compound (SMILES): CN(C)c1nc2ccccn2c1-c1ccc(O)cc1
InChIKey: WHEMRCRGZRRMCK-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O94782
Assay: Inhibition of USP1 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 253.31, ALogP 2.77, HBA 4, HBD 1, PSA 40.77, QED 0.76
Compound (SMILES): COc1c(-c2cc(-c3ccccc3)n(-c3ccc(C#N)cc3)n2)ccc2occc12
InChIKey: MEXURXCEUNSVJA-UHFFFAOYSA-N
Target: Cytochrome P450 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16678
Assay: Inhibition of human CYP1B1 expressed in sacchrosomes using 7-ethoxyresorufin as substrate by fluorescence based assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 391.43, ALogP 5.83, HBA 5, HBD 0, PSA 63.98, QED 0.39
Compound (SMILES): O=C(O)c1cc(-c2ccc(Cl)c(OC3CC3)c2)ncn1
InChIKey: SIYCDJHEVASOGW-UHFFFAOYSA-N
Target: Kynurenine 3-monooxygenase (SINGLE PROTEIN), Mus musculus
UniProt: Q91WN4
Assay: Inhibition of mouse liver mitochondrial KMO by measuring the 3-HK metabolite formation using L-kynurenine as substrate preincubated for 5 mins followed by substate addition and measured after 30 mins by LC-MS/MS analysis
Measurement: IC50 = 8.7 nM (pChEMBL 8.0600004196167)
Descriptors: MW 290.71, ALogP 3.04, HBA 4, HBD 1, PSA 72.31, QED 0.94
Compound (SMILES): CNC(=N)N/N=C(/C)c1ccc2oc3ccc(/C(C)=N/NC(=N)NC)cc3c2c1
InChIKey: GDRFOQDJRLEMDH-UIXGLJBASA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Inhibition of recombinant GST-tagged CARM1 (unknown origin) expressed in Escherichia coli using histone H3.3 peptide as substrate incubated for 120 mins in presence of [3H]-SAM cofactor by radioactive filter plate assay
Measurement: IC50 = 15500 nM (pChEMBL 4.809999942779541)
Descriptors: MW 392.47, ALogP 2.52, HBA 5, HBD 6, PSA 133.68, QED 0.23
Compound (SMILES): Clc1cccc(-c2ccc(OCCCN3CCN(c4ccncc4)CC3)cc2)c1
InChIKey: VFWVIGRCTIKWRY-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of [3H]UR-DE257 from Gsalphas-coupled human H2R expressed in Sf9 cell membranes measured after 60 mins by scintillation counting analysis
Measurement: Ki = 5487 nM (pChEMBL 5.260000228881836)
Descriptors: MW 407.95, ALogP 4.99, HBA 4, HBD 0, PSA 28.6, QED 0.52
Compound (SMILES): N#CC1(NC(=O)[C@@H](Cc2ccccc2)NS(=O)(=O)c2cccc(-c3ccccc3)c2)CC1
InChIKey: JFDASADTBFBMEF-HSZRJFAPSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of human cathepsin L using Phe-Arg-pNA as substrate measured after 60 mins by spectrophotometric assay
Measurement: Ki = 343 nM (pChEMBL 6.460000038146973)
Descriptors: MW 445.54, ALogP 3.42, HBA 4, HBD 2, PSA 99.06, QED 0.55
Compound (SMILES): N#Cc1c(-c2ccc(Cl)cc2)cn(-c2ccc(S(N)(=O)=O)cc2)c1/N=C/c1ccc([N+](=O)[O-])cc1
InChIKey: KEINPWRSVRHLNM-CCVNUDIWSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 1136.4 nM (pChEMBL 5.940000057220459)
Descriptors: MW 505.94, ALogP 4.98, HBA 7, HBD 1, PSA 144.38, QED 0.22
Compound (SMILES): CC(C)CC(=O)Nc1cncc(-c2ccc3[nH]nc(-c4cc5c(-c6cc(F)cc(CNS(C)(=O)=O)c6)nccc5[nH]4)c3n2)c1
InChIKey: RYSHRLOQNZGTNI-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 612.69, ALogP 5.4, HBA 7, HBD 4, PSA 158.41, QED 0.17
Compound (SMILES): C/C=C/C(=O)Nc1cccc(-c2cc(Nc3cnn(CCO)c3)ncn2)c1
InChIKey: GELODAVSSQEIEG-DUXPYHPUSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human GST-tagged JAK1 cytoplasmic domain (866 to 1154 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 2443 nM (pChEMBL 5.610000133514404)
Descriptors: MW 364.41, ALogP 2.59, HBA 7, HBD 3, PSA 104.96, QED 0.56
Compound (SMILES): O=C(Cn1nc2cccnn2c1=O)NC1(c2cccc(Cl)c2)CC1
InChIKey: DAJRHZBLOSVJEC-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 >= 100 nM (pChEMBL 7)
Descriptors: MW 343.77, ALogP 1.35, HBA 6, HBD 1, PSA 81.29, QED 0.77
Compound (SMILES): C=CC(=O)NCC(NC(=O)[C@@H](NC(C)=O)[C@@H](C)CC)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@]1(C)CCC/C=C/CCC[C@@](C)(C(=O)N[C@@H](Cc2ccccc2)C(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H]([C@@H](C)CC)NC1=O)[C@@H](C)CC
InChIKey: IQRCBNCNTIDZQV-IMXCUJBUSA-N
Target: Bcl-2-related protein A1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16548
Assay: Covalent binding affinity to human Bcl2A1 by FBid based FP assay
Measurement: Ki = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 1706.02
Compound (SMILES): COc1ccc(-n2nnc3cnc(N[C@@H]4CC[C@@H](N)C4)nc32)cc1
InChIKey: OSHLPUOBFBCDRP-GHMZBOCLSA-N
Target: Mitogen-activated protein kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16659
Assay: Binding affinity to LPP-dephosphorylated recombinant wild-type ERK3 (9 to 327 residues) (unknown origin) expressed in Escherichia coli by microscale thermophoresis assay
Measurement: Kd = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 325.38, ALogP 1.51, HBA 8, HBD 2, PSA 103.77, QED 0.75
Compound (SMILES): CC(C(=O)N[C@@H](C)c1ccc(Cl)c(F)c1)n1nc2cccnn2c1=O
InChIKey: NZRFPISYXWDFOY-RGURZIINSA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P0C0W8
Assay: Agonist activity at rat GPR139 expressed in CHO-K1 cells assessed as increase in calcium flux by calcium 5 dye based FLIPR assay
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 363.78, ALogP 2.12, HBA 6, HBD 1, PSA 81.29, QED 0.77
Compound (SMILES): CC1(C)Cc2c(-c3cc(NC(=O)[C@H]4C[C@@H](O)C4)ncc3Cl)cnn2C1
InChIKey: BJVQHPTYDFVVJV-PHIMTYICSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of recombinant full length human N-terminal GST-fused CDK9 (1 to 372 residues)/His-tagged CyclinT1 (1 to 726 residues) expressed in baculovirus infected insect cells using FITC-X-GSRTPMY-NH2 as substrate preincubated for 10 mins followed by MgCl2 addition and measured after 90 mins in presence of 5 mM ATP by mobility shift assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 360.85, ALogP 2.89, HBA 5, HBD 2, PSA 80.04, QED 0.88
Compound (SMILES): C[C@@H](NC(=O)C1CCCCC1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: WMHOQRCAAUMCMZ-KURKYZTESA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells preincubated for 2 hrs followed by IFNgamma stimulation and measured after 18 hrs by
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 382.52, ALogP 5.73, HBA 2, HBD 1, PSA 41.99, QED 0.73
Compound (SMILES): COc1ccc(C(Oc2ccc(N(CC(=O)O)S(=O)(=O)c3c(C)cc(C)cc3C)c3ccccc23)C(=O)O)cc1
InChIKey: SNWXNMFUFJGUTF-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes preincubated for 10 mins followed by NADPH addition by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 563.63, ALogP 5.26, HBA 6, HBD 2, PSA 130.44, QED 0.27
Compound (SMILES): Nc1nc(N2CCC3(CC2)COC[C@H]3N)cnc1Sc1ccnc(N)c1Cl
InChIKey: OMJHHTRDBKAMSN-LLVKDONJSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by Q-patch assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 407.93, ALogP 1.78, HBA 9, HBD 3, PSA 129.2, QED 0.7
Compound (SMILES): Cn1cc(-c2cn3nccc3c(-c3cnn([C@]4(CC#N)C[C@H](C#N)C4)c3)n2)cn1
InChIKey: XPLZTJWZDBFWDE-LDTOLXSISA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: JAK Caliper Enzyme Assay at 1 mM ATP: Compounds were added to a 384-well plate. Reaction mixtures contained 10 mM HEPES, pH 7.4, 10 mM MgCl2, 0.01% BSA, 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAM-KKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20% to 30% phosphorylation. The assays were stopped with 15 μL of 180 mM HEPES, pH 7.4, 20 mM EDTA, and 0.2% Coating Reagent 3. The assay plates were placed on a Caliper Life Science LC3000 instrument, and each well was sampled using appropriate separation conditions to measure the unphosphorylated and phosphorylated peptide.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 383.42, ALogP 2.54, HBA 9, HBD 0, PSA 113.41, QED 0.53
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=O)CCN2CCN(c3ncccn3)CC2)cc1
InChIKey: DYMIXDAYDQNVPD-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 by stopped-flow CO2 hydration assay
Measurement: Ki = 377.4 nM (pChEMBL 6.420000076293945)
Descriptors: MW 404.5, ALogP -0.05, HBA 7, HBD 2, PSA 121.52, QED 0.66
Compound (SMILES): Cc1c(-c2c(N)nn3ccc(-c4cc5c(c(C(F)(F)F)c4)C(=O)N([C@@H](C)C4CC4)C5)nc23)cnn1C
InChIKey: USPUQVAHEMNGFE-LBPRGKRZSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant N-terminal GST-tagged full-length human PI3K p110delta/p85alpha co- expressed in Sf9 insect cells using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 60 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP-Glo lipid kinase assay
Measurement: IC50 = 2240 nM (pChEMBL 5.650000095367432)
Descriptors: MW 495.51, ALogP 4.46, HBA 7, HBD 1, PSA 94.34, QED 0.45
Compound (SMILES): Cn1c2ccccc2c(=O)c2c(=O)[nH]c(C3CCCC3)nc21
InChIKey: FDDXGERFFWUUGA-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Positive allosteric modulator activity at human dopamine D1 receptor expressed in HEK293 cells assessed as potentiation of dopamine-induced cAMP accumulation by measuring dopamine EC50 at 50 uM measured after 30 mins by HitHunter assay (Rvb = 214 nM)
Measurement: EC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 295.34, ALogP 2.43, HBA 4, HBD 1, PSA 67.75, QED 0.7
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(NC(=O)CCCCCCNC(=O)CNc2cccc3c2C(=O)N(C2CCC(=O)NC2=O)C3=O)cc1
InChIKey: WXWAPGNHECFJAW-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of human recombinant C-terminal His-tagged HDAC3 (1 to 428 residues)/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in baculovirus infected Sf9 insect cells using Boc-Lys(epsilon-Ac)-AMC as substrate measured after 90 mins by fluorescence assay
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 667.72, ALogP 3.04, HBA 9, HBD 6, PSA 208.9, QED 0.08
Compound (SMILES): Cc1c(Br)cc(C(=O)NC2CCNCC2)c(=O)n1Cc1ccc(F)cc1
InChIKey: PDHOGOAIZVGCIX-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of FAAH in human U937 cells using [ethanolamine-1-3H]AEA as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 422.3, ALogP 2.59, HBA 4, HBD 2, PSA 63.13, QED 0.8
Compound (SMILES): CNCC[C@H](Oc1cccc(N2CCN(C)c3ncncc3C2=O)c1)c1cccs1
InChIKey: KYQUYMHBNNIIFU-IBGZPJMESA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Inhibition of human NET expressed in HEK293 cells assessed as reduction in ASP+ uptake incubated for 20 mins before ASP+ addition and measured after 90 mins by scintillation counting method
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 423.54, ALogP 3.36, HBA 7, HBD 1, PSA 70.59, QED 0.63
Compound (SMILES): Cn1cc2cc(-c3cnc(Nc4cnc(C#N)cn4)cc3NC[C@H]3CNCCO3)ccc2n1
InChIKey: ICXIWZZELJHOKA-GOSISDBHSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]astemizole from human ERG expressed in HEK293 cells by radioligand binding assay
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 441.5, ALogP 2.44, HBA 10, HBD 3, PSA 125.6, QED 0.41
Compound (SMILES): CCOc1ccc2oc(CC)cc2c1[C@H]1C[C@@H]1CN.Cl
InChIKey: MNQCDAZSMTUQCZ-IYJPBCIQSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5-HT2B receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 309.03 nM (pChEMBL 6.510000228881836)
Descriptors: MW 259.35, ALogP 3.46, HBA 3, HBD 1, PSA 48.39, QED 0.89
Compound (SMILES): Nc1nccc(-c2c3cccnc3n3c(N)nccc23)n1
InChIKey: JTQQDEMYPLKSDW-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of human recombinant CDK9 (773 to 928 residues) expressed in insect cells
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 277.29, ALogP 1.5, HBA 7, HBD 2, PSA 108.01, QED 0.55
Compound (SMILES): CO[C@@]12CC[C@H](N[C@@H](CC(=O)O)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: MNYBENXVWGLZEJ-OXNBKUEFSA-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 membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 50.2 nM (pChEMBL 7.300000190734863)
Descriptors: MW 432.47, ALogP 0.72, HBA 7, HBD 4, PSA 128.56, QED 0.51
Compound (SMILES): CCCCCCCCCCCOc1ccccc1CCC(=O)O[C@@H]1CCOC[C@@H]1OP(=O)(O)OC[C@H](N)C(=O)O
InChIKey: WTHILFAMRXZBRN-DMDYGQEQSA-N
Target: Putative P2Y purinoceptor 10 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BFU7
Assay: Agonist activity at mouse P2Y10 expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis
Measurement: EC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 587.65, ALogP 4.78, HBA 9, HBD 3, PSA 163.84, QED 0.1
Compound (SMILES): CC1N(S(=O)(=O)c2ccc(F)cc2)c2ccc(C(=O)NCc3ccccc3Cl)cc2C12CCNCC2
InChIKey: UASMEFJXHIESFN-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Antagonist activity at human GnRH receptor expressed in CHO-K1 cells assessed as inhibition of buserelin-induced response preincubated for 20 mins followed by buserelin addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 172 nM (pChEMBL 6.760000228881836)
Descriptors: MW 528.05, ALogP 4.63, HBA 4, HBD 2, PSA 78.51, QED 0.51
Compound (SMILES): C[C@](O)(Cn1ccc(F)n1)C(=O)Nc1ccc(C#N)c(C(F)(F)F)c1
InChIKey: VPINQEFVSVMLJX-AWEZNQCLSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Human Androgen Receptor (hAR) Ligand Binding Domain (LBD) Affinity Assay: Methods: hAR-LBD (633-919) was cloned into pGex4t.1. Large scale GST-tagged AR-LBD was prepared and purified using a GST column. Recombinant AR-LBD was combined with [3H]mibolerone (PerkinElmer, Waltham, Mass.) in buffer A (10 mM Tris, pH 7.4, 1.5 mM disodium EDTA, 0.25 M sucrose, 10 mM sodium molybdate, 1 mM PMSF) to determine the equilibrium dissociation constant (Kd) of [3H]mibolerone. Protein was incubated with increasing concentrations of [3H]mibolerone with and without a high concentration of unlabeled mibolerone at 4° C. for 18 h in order to determine total and non-specific binding. Non-specific binding was then subtracted from total binding to determine specific binding and non-linear regression for the ligand binding curve with one site saturation was used to determine the Kd of mibolerone.Increasing concentrations of SARDs or DHT (range: 10−12 to 10−4 M) were incubated with [3H]mibolerone and AR-LBD using the conditions described above. Following incubation, the ligand bound AR-LBD complex was isolated using BiogelHT hydroxyapatite, washed and counted in a scintillation counter after adding scintillation cocktail.
Measurement: Ki = 821 nM (pChEMBL 6.090000152587891)
Descriptors: MW 356.28, ALogP 2.3, HBA 5, HBD 2, PSA 90.94, QED 0.82
Compound (SMILES): COc1ccc(C2CNC(=O)C2NC(=O)Nc2ccc(Cl)cc2)cc1
InChIKey: KHWQLQMKSMNUBQ-UHFFFAOYSA-N
Target: fMet-Leu-Phe receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21462
Assay: Agonist activity at human FPR1 expressed in HEK 293 cells co-expressing Galpha15 measured every 1.5 sec for 80 sec by Fluo-4 NW staining based scanning fluorometric method
Measurement: EC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 359.81, ALogP 2.75, HBA 3, HBD 3, PSA 79.46, QED 0.78
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(N5CCNCC5)cc4)ccn23)c2ccccc2n1
InChIKey: KVDFCDPSKGACEZ-UHFFFAOYSA-N
Target: Bone morphogenetic protein receptor type-1A (SINGLE PROTEIN), Homo sapiens
UniProt: P36894
Assay: Inhibition of human ALK3 using casein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 419.53, ALogP 4.93, HBA 5, HBD 1, PSA 45.46, QED 0.45
Compound (SMILES): Cc1c(C#N)cccc1-c1cc(-c2cn(Cc3cccc(C(C)(C)O)n3)nn2)nc(N)n1
InChIKey: BUXIAWLTBSXYSW-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Antagonist activity at adenosine 2A receptor (unknown origin)
Measurement: Ki = 0.8511 nM (pChEMBL 9.069999694824219)
Descriptors: MW 426.48, ALogP 2.84, HBA 9, HBD 2, PSA 139.42, QED 0.5
Compound (SMILES): C=CCn1c(SCC(=O)Nc2ccc(/C(C)=N\O)cc2)nnc1-c1cc(-c2ccc(Cl)cc2)nc2ccccc12
InChIKey: QOZIUJUUHPTKBC-WBIBEUCMSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of STAT3 in human SB-590885-resistant 451Lu cells assessed as reduction in STAT3 transcriptional activity measured after 12 hrs by Dual-luciferase reporter gene assay
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 569.09, ALogP 6.93, HBA 8, HBD 2, PSA 105.29, QED 0.07
Compound (SMILES): CC(C)n1cc(-c2nc(Nc3ccc4c(c3)CCN(C(=O)CO)C4)ncc2F)cn1
InChIKey: PAUJMQGNHPBPDQ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant in human MOLM13 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay
Measurement: IC50 = 453 nM (pChEMBL 6.340000152587891)
Descriptors: MW 410.45, ALogP 2.68, HBA 7, HBD 2, PSA 96.17, QED 0.67
Compound (SMILES): O=C(CCN1CCCc2ccccc21)NCc1cccc(F)c1
InChIKey: ZZTZWBOESPTHOA-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from muscarinic M2 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 1905.46 nM (pChEMBL 5.71999979019165)
Descriptors: MW 312.39, ALogP 3.28, HBA 2, HBD 1, PSA 32.34, QED 0.92
Compound (SMILES): CC(C)c1cc(-c2c(N)nn3ccc(-c4cc5c(c(C(F)(F)F)c4)C(=O)N([C@@H](C)C4CC4)C5)nc23)ccc1C(=O)O
InChIKey: MYIWJCONSHUYIA-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant N-terminal His-tagged full-length human PI3K p120gamma expressed in Sf9 insect cells using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 60 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP-Glo lipid kinase assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 563.58, ALogP 6.24, HBA 6, HBD 2, PSA 113.82, QED 0.29
Compound (SMILES): C[C@H]1C[C@@H](Oc2cc(Cl)cc(NC(=O)CC(CCC(=O)O)c3ccccc3)c2Cl)CCN1C(=O)C1CCCC1
InChIKey: NWXXXIQTJWEGQR-UIEAFCHPSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at GAL4-fused RORgammat (unknown origin) transfected in HEK293T cells assessed as inhibition of RORgammat driven transcriptional activity by dual-luciferase reporter gene assay
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 575.53, ALogP 6.92, HBA 4, HBD 2, PSA 95.94, QED 0.32
Compound (SMILES): CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1NC(=O)c1cc(Br)c(C)n(Cc2ccc(F)cc2)c1=O
InChIKey: HBOVCHXLXXSXTK-DRJBRKBZSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of FAAH in human U937 cells using [ethanolamine-1-3H]AEA as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 542.36, ALogP -0.22, HBA 8, HBD 5, PSA 150.12, QED 0.34
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2cccc(C(F)(F)F)c2)CC1
InChIKey: BMEHLDKQUOMXTR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in ERK1/2 phosphorylation after 15 mins by Alphalisa assay
Measurement: EC50 = 56.23 nM (pChEMBL 7.25)
Descriptors: MW 476.87, ALogP 5.11, HBA 3, HBD 1, PSA 41.57, QED 0.45
Compound (SMILES): CN1CC2CCC(C1)N2C(=O)Nc1cc2cc(-c3cnn(C)c3)ccc2cn1
InChIKey: POZRJQXLKAMXDW-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 376.46, ALogP 2.95, HBA 5, HBD 1, PSA 66.29, QED 0.75
Compound (SMILES): Cc1cc(-c2ccn3nc(N)c(-c4nc[nH]n4)c3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: MUOBADCHUJUBIR-LBPRGKRZSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant N-terminal GST-tagged full-length human PI3K p110delta/p85alpha co- expressed in Sf9 insect cells using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 60 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP-Glo lipid kinase assay
Measurement: IC50 = 6050 nM (pChEMBL 5.21999979019165)
Descriptors: MW 414.47, ALogP 2.83, HBA 7, HBD 2, PSA 118.09, QED 0.53
Compound (SMILES): O=C(c1ccc2occc2c1)N1CCCC(c2ccnc3ncnn23)C1
InChIKey: HNDPBXHAFBXLSC-UHFFFAOYSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13370
Assay: Inhibition of 6xHis-tagged human recombinant PDE3B expressed in Sf9 cells in presence of [3H]-cAMP and cAMP incubated for 60 mins by scintillation counting method
Measurement: IC50 = 1622 nM (pChEMBL 5.789999961853027)
Descriptors: MW 347.38, ALogP 2.89, HBA 6, HBD 0, PSA 76.53, QED 0.56
Compound (SMILES): CO[C@@]12CC[C@@H](NCCCC(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: HAVQMMOFQDNJHT-HAOCKTTRSA-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 membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 147 nM (pChEMBL 6.829999923706055)
Descriptors: MW 402.49, ALogP 1.65, HBA 6, HBD 3, PSA 91.26, QED 0.62
Compound (SMILES): Nc1nc(-c2ccccn2)nn1C(=O)Cc1ccccc1
InChIKey: WLZYFEBXZVJFMV-UHFFFAOYSA-N
Target: Coagulation factor XII (SINGLE PROTEIN), Homo sapiens
UniProt: P00748
Assay: Inhibition of human coagulation factor XIIA using Boc-Gln-Gly-Arg-AMC as fluorogenic substrate measured at 1 min interval for 1 hr by fluorometric assay
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 279.3, ALogP 1.81, HBA 6, HBD 1, PSA 86.69, QED 0.79
Compound (SMILES): COc1cnc2nn(CC(=O)N[C@@H](C)c3ccc(OC(F)(F)F)cc3)c(=O)n2c1
InChIKey: AAHFBGAZUBPXAA-JTQLQIEISA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 411.34, ALogP 1.68, HBA 8, HBD 1, PSA 99.75, QED 0.66
Compound (SMILES): Cc1ccc(-n2c(CC3CCCCC3)nc3c(c(=O)c4ccccc4n3C)c2=O)cc1
InChIKey: LSQLGWAUFNCJKV-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Positive allosteric modulator activity at human dopamine D1 receptor expressed in HEK293 cells assessed as potentiation of dopamine-induced cAMP accumulation by measuring dopamine EC50 at 50 uM measured after 30 mins by HitHunter assay (Rvb = 214 nM)
Measurement: EC50 = 276 nM (pChEMBL 6.559999942779541)
Descriptors: MW 413.52, ALogP 4.67, HBA 5, HBD 0, PSA 56.89, QED 0.46
Compound (SMILES): C[C@]1(c2cc(/C=C(\F)c3ccc(C#N)cn3)ccc2F)N=C(N)S[C@@]2(C(=O)N3CCCC3)C[C@H]21
InChIKey: BVIPSJSEJQGVKV-MYMUPAQMSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of recombinant human BACE2 using fluorescence substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by FRET assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 479.56, ALogP 4.22, HBA 6, HBD 1, PSA 95.37, QED 0.71
Compound (SMILES): Cn1ncc(-c2ccc3cnc(NC(=O)c4cccc(CN5CCCC5)c4)cc3c2)c1CN1CCCCC1
InChIKey: KXSODQSDAXBEHN-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 508.67, ALogP 5.47, HBA 6, HBD 1, PSA 66.29, QED 0.36
Compound (SMILES): C[C@H](NC(=O)Cn1nc2cc(N3CCOCC3)cnn2c1=O)c1ccc(Cl)c(F)c1
InChIKey: SVQZKEIFULDYKQ-LBPRGKRZSA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 >= 100 nM (pChEMBL 7)
Descriptors: MW 434.86, ALogP 1.4, HBA 8, HBD 1, PSA 93.76, QED 0.65
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](CS)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: HTRPGUCLEKHUTO-AKSMUQGVSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at kappa opioid receptor (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 74.13 nM (pChEMBL 7.130000114440918)
Descriptors: MW 1119.34
Compound (SMILES): Cc1cc(C)c(CN2CCc3c(Br)cc(-c4c(C)nnn4C)c(Cl)c3C2=O)c(=O)[nH]1
InChIKey: GIDGCOVAJNOCKD-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of wild type EZH2 in human KARPAS-422 cells assessed as effect on H3K27Me3 levels
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 490.79, ALogP 3.71, HBA 5, HBD 1, PSA 83.88, QED 0.61
Compound (SMILES): COc1ccc(OC)c2c1c(OC)cc1c(=O)cc(-c3cccc(N4CCOCC4)c3)oc12
InChIKey: IGLXPSUCFZANQH-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethoxyresorufin as substrate after 50 mins in presence of NADP+ by EROD assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 447.49, ALogP 4.48, HBA 7, HBD 0, PSA 70.37, QED 0.42
Compound (SMILES): C/C(=C\COc1ccccc1Cc1c(C)nnn1-c1ccc(-c2ccco2)cc1)CCC(=O)O
InChIKey: UUIVQMMTYKIWMH-XDJHFCHBSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Modulator activity at GAL4-fused human PPARgamma LBD (unknown origin) transfected in African green monkey CV1 cells assessed as receptor transactivation by luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 457.53, ALogP 5.62, HBA 6, HBD 1, PSA 90.38, QED 0.31
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)CN(Cc2ccccc2)C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: PTAWHKBYGNKZHT-NETOACFBSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse MC3R assessed as antagonist potency by alphascreen cAMP assay
Measurement: Kd = 1000 nM (pChEMBL 6)
Descriptors: MW 977.14, ALogP -0.92, HBA 10, HBD 9, PSA 311.42, QED 0.06
Compound (SMILES): CN(C)Cc1cncc(-c2ccc3[nH]nc(-c4cc5c(N6CCCCC6)nccc5[nH]4)c3c2)c1
InChIKey: DXKDNTIIMDTBJP-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 293 nM (pChEMBL 6.53000020980835)
Descriptors: MW 451.58, ALogP 5.22, HBA 5, HBD 2, PSA 76.73, QED 0.38
Compound (SMILES): CC(C(=O)Nc1cc(C2CC2)[nH]n1)c1ccc(-c2ccc(NC(=O)/C=C/CN3CCOCC3)nc2)cc1
InChIKey: JDHQEFMWJITKOK-NSCUHMNNSA-N
Target: Cyclin-dependent kinase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14004
Assay: Inhibition of kinase tracer 236 binding to CDK13 (unknown origin) by FRET based Lantha screen Eu kinase binding assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 500.6, ALogP 3.92, HBA 6, HBD 3, PSA 112.24, QED 0.38
Compound (SMILES): CC(C)C(NC1=NS(=O)(=O)c2ccccc21)C(=O)NC[C@@H](NC(=O)CC1(NC(=O)[C@H](CC(C)(C)C)n2cc(CC3CCCCC3)nn2)CCCCC1)C(N)=O
InChIKey: VZVPVCFZEIWTEG-QRBFTZNISA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Binding affinity to N-terminal GST-tagged recombinant human PTP1B (1 to 321 residues) expressed in Escherichia coli assessed as dissociation constant and measured for 120 sec by biolayer interferometry
Measurement: Kd = 100 nM (pChEMBL 7)
Descriptors: MW 782.02, ALogP 3.44, HBA 10, HBD 5, PSA 219.63, QED 0.18
Compound (SMILES): c1ccc(CC2CCN(C3CCc4ccccc4C3)CC2)cc1
InChIKey: VFXPONVZYRUQFR-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from sigma 2 receptor in rat liver membranes incubated for 120 mins by scintillation counting method
Measurement: Ki = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 305.46, ALogP 4.5, HBA 1, HBD 0, PSA 3.24, QED 0.81
Compound (SMILES): Cc1cc(-c2ccn3ncc(-c4cnn(C)c4)c3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: ICAXSMPZWOGABB-HNNXBMFYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant N-terminal GST-tagged full-length human PI3K p110delta/p85alpha co- expressed in Sf9 insect cells using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 60 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP-Glo lipid kinase assay
Measurement: IC50 = 3440 nM (pChEMBL 5.460000038146973)
Descriptors: MW 412.5, ALogP 3.86, HBA 6, HBD 0, PSA 68.32, QED 0.51
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCN(CC(=O)N(C)C)C2
InChIKey: WREJSHALYATLCM-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 573.12, ALogP 4.25, HBA 9, HBD 2, PSA 116.76, QED 0.39
Compound (SMILES): CCc1cccc(NC(=O)CSc2nc3ccc(I)cc3c(=O)n2-c2ccc(S(N)(=O)=O)cc2)c1
InChIKey: LLFRMUXSDAUEPX-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 172.6 nM (pChEMBL 6.760000228881836)
Descriptors: MW 620.49, ALogP 3.93, HBA 7, HBD 2, PSA 124.15, QED 0.18
Compound (SMILES): O=c1c2cc(-c3cn[nH]c3)ccc2ncn1Cc1ccccc1
InChIKey: PBKHWCKJJPVRRM-UHFFFAOYSA-N
Target: G protein-coupled receptor kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P34947
Assay: Binding affinity to GRK5 (unknown origin) by Thermofluor thermal shift assay
Measurement: Kd = 34300 nM (pChEMBL 4.460000038146973)
Descriptors: MW 302.34, ALogP 2.83, HBA 4, HBD 1, PSA 63.57, QED 0.63
Compound (SMILES): Cc1cc(C(=O)Nc2c(Cl)ccc(NS(=O)(=O)c3cc(F)ccc3F)c2F)c2ncnc(NCCN)c2c1
InChIKey: OUYVKASWKZDQCL-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of of human recombinant His6-tagged B-Raf V600E mutant expressed in baculovirus infected cells co-expresing CDC37 in presence of [gamma33P]ATP incubated for 60 mins by scintillation counting method
Measurement: Ki = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 564.98, ALogP 4.43, HBA 7, HBD 4, PSA 139.1, QED 0.25
Compound (SMILES): O=C(N/N=C/c1ccc(Cl)cc1)N1CCN(c2ccccn2)CC1
InChIKey: SVGUUFXJKYXVCE-DEDYPNTBSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocytes AChE using acetylthiocholine iodide as substrate preincubated for 10 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 3420 nM (pChEMBL 5.46999979019165)
Descriptors: MW 343.82, ALogP 2.6, HBA 4, HBD 1, PSA 60.83, QED 0.69
Compound (SMILES): COc1ccc(-n2c(C3CCCCC3)nc3c(c(=O)c4ccccc4n3C)c2=O)cc1
InChIKey: VDPJWVIWNFNUPS-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Positive allosteric modulator activity at human dopamine D1 receptor expressed in HEK293 cells assessed as potentiation of dopamine-induced cAMP accumulation by measuring dopamine EC50 at 50 uM measured after 30 mins by HitHunter assay (Rvb = 214 nM)
Measurement: EC50 = 185 nM (pChEMBL 6.730000019073486)
Descriptors: MW 415.49, ALogP 4.29, HBA 6, HBD 0, PSA 66.12, QED 0.47
Compound (SMILES): Cc1c(CN2CCN(C(=O)C3CCCC3)[C@@H](C)C2)cc(F)cc1NC(=O)CC(CCC(=O)O)c1nccs1
InChIKey: ITBYSAKYNRBPRQ-YMXDCFFPSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at GAL4-fused RORgammat (unknown origin) transfected in HEK293T cells assessed as inhibition of RORgammat driven transcriptional activity by dual-luciferase reporter gene assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 544.69, ALogP 4.79, HBA 6, HBD 2, PSA 102.84, QED 0.45
Compound (SMILES): CN(C)CCNc1cc(F)cc(-c2cncc3[nH]c(-c4n[nH]c5ncc(-c6cccnc6)cc45)nc23)c1
InChIKey: MQYKHRCDYACKTE-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 493.55, ALogP 4.74, HBA 7, HBD 3, PSA 111.3, QED 0.29
Compound (SMILES): COc1ccc(S(=O)(=O)N2c3ccc(C(=O)NCc4ccccc4Cl)cc3C(C)(C)C2C)cc1
InChIKey: KIJIVGJUSQHRON-UHFFFAOYSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Antagonist activity at human GnRH receptor expressed in CHO-K1 cells assessed as inhibition of LHRH-induced response preincubated for 20 mins followed by LHRH addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 568 nM (pChEMBL 6.25)
Descriptors: MW 499.03, ALogP 5.15, HBA 4, HBD 1, PSA 75.71, QED 0.51
Compound (SMILES): COc1ccc(OC)c2c1c(OC)cc1c(=O)cc(-c3cccnc3O)oc12
InChIKey: VUAAPEQWEPEZIZ-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethoxyresorufin as substrate after 50 mins in presence of NADP+ by EROD assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 379.37, ALogP 3.74, HBA 7, HBD 1, PSA 91.02, QED 0.54
Compound (SMILES): Cc1cn(-c2nccc3[nH]c(-c4n[nH]c5ccc(-c6cncc(NC(=O)CC(C)C)c6)cc45)nc23)cn1
InChIKey: WYEVYCHVIMTLKF-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 491.56, ALogP 5.04, HBA 7, HBD 3, PSA 130.06, QED 0.3
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nc2ccc(F)cn2c1-c1ccccc1S(C)(=O)=O
InChIKey: OMGSGYMWIPFOES-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant full length N-terminal polyHis-tagged PI3Kgamma (114 to 1102 residues) (unknown origin) expressed in baculovirus infected Hi-5 cells using PIP2 as substrate in presence of ATP incubated for 20 mins by Alphascreen assay
Measurement: IC50 = 63400 nM (pChEMBL 4.199999809265137)
Descriptors: MW 451.49, ALogP 2.96, HBA 9, HBD 2, PSA 139.06, QED 0.47
Compound (SMILES): C#Cc1cnc(Nc2cnc(C#N)cn2)cc1NC[C@@H]1CNCCO1
InChIKey: SPYAJJPHDPVEBQ-AWEZNQCLSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]astemizole from human ERG expressed in HEK293 cells by radioligand binding assay
Measurement: IC50 = 8200 nM (pChEMBL 5.090000152587891)
Descriptors: MW 335.37, ALogP 0.87, HBA 8, HBD 3, PSA 107.78, QED 0.69
Compound (SMILES): CC(C)(C#Cc1cccc(-c2nn(-c3nc(C(=O)O)cs3)c(CCC3CC3)c2Cc2ccc(S(N)(=O)=O)c(F)c2)c1)C1CC1
InChIKey: IWNUFUXIRNVXPN-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 5144 nM (pChEMBL 5.289999961853027)
Descriptors: MW 632.78, ALogP 6.2, HBA 7, HBD 2, PSA 128.17, QED 0.2
Compound (SMILES): COc1cc(OC)c(Cl)c(COc2cnc(Nc3c(C)cccc3NC(=O)C3CO3)nc2)c1Cl
InChIKey: ZPFOOLKMDLORHG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of recombinant human His-tagged FGFR2 (403 to 822 residues) cytoplasmic domain expressed in baculovirus expression system using Tyr 04 peptide as substrate after 1 hr in presence of ATP by Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 505.36, ALogP 4.77, HBA 8, HBD 2, PSA 107.13, QED 0.4