lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC)C(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@H](C)C(=O)O
InChIKey: NGVJFCSAEWHFBV-ZWOKYPKOSA-N
Target: Type-1 angiotensin II receptor A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25095
Assay: Agonist activity at rat AT1aR expressed in HEK293 cells incubated for 60 mins by luminescence based beta-arrestin recruitment assay
Measurement: EC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 940.12, ALogP -1.52, HBA 12, HBD 13, PSA 355.05, QED 0.03
Compound (SMILES): COc1ccc(-c2cc(CN3C(=O)c4ccccc4S3(=O)=O)on2)cc1
InChIKey: LPLAHTFFLPLMHY-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 22.1 nM (pChEMBL 7.659999847412109)
Descriptors: MW 370.39, ALogP 2.69, HBA 6, HBD 0, PSA 89.71, QED 0.7
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)O)c(CC(=O)O)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: DRCQLRCTICYAAL-WOJBJXKFSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 531.56, ALogP 2.9, HBA 7, HBD 5, PSA 186.48, QED 0.07
Compound (SMILES): COc1cc(O)c2c(c1)-c1cccc(c1)[C@H](O)[C@@H](O)C(=O)CCC[C@H](C)OC2=O
InChIKey: REIUSODTVBSVPQ-ALHNEKMOSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human FLT3 using EAIYAAPFAKKK substrate and [gamma-33P]-ATP by radiometric biochemical kinase assay
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 400.43, ALogP 2.76, HBA 7, HBD 3, PSA 113.29, QED 0.63
Compound (SMILES): C[C@@H]1CCCN1CCCOc1ccc2c(c1)CC[C@H]1[C@@H]3[C@@H](C(=O)NCC4CC4)CC[C@@]3(C)CC[C@H]21
InChIKey: XVTLHDIVQKIZDR-DMRQYYOESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 478.72, ALogP 5.94, HBA 3, HBD 1, PSA 41.57, QED 0.47
Compound (SMILES): Cc1nc(-c2ccccc2)sc1C(=O)NC1CC1
InChIKey: ZZAWMNWRQROJSY-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at N-terminal Flag epitope tagged CB2 (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 258.35, ALogP 3.01, HBA 3, HBD 1, PSA 41.99, QED 0.92
Compound (SMILES): Clc1cc(NC2CCOCC2)c2ncc(-c3ccc4[nH]c(Nc5ccccc5)nc4c3)n2n1
InChIKey: TWUAZGWGHKZNTE-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Inhibition of dephosphorylated IRE1alpha (G547 to L977 residues) (unknown origin) autophosphorylation at S724 after 25 mins in presence of ATP by dissociation-enhanced lanthanide fluorescence immunoassay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 459.94, ALogP 5.26, HBA 7, HBD 3, PSA 92.16, QED 0.33
Compound (SMILES): COC(=O)N[C@@H]1Cc2ccc(cc2)NC(=O)CCN2CCN(CCC(=O)Nc3ccc(cc3)C[C@@H](C(=O)NCc3ccc(C(=N)N)cc3)NC1=O)CC2.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: MDWMQNUVZXFTRT-ORZGUCGRSA-N
Target: Prothrombin (SINGLE PROTEIN), Bos taurus
UniProt: P00735
Assay: Inhibition of bovine thrombin using Tos-Gly-Pro-Arg-AMC as substrate by Dixon plot analysis
Measurement: Ki = 15290 nM (pChEMBL 4.820000171661377)
Descriptors: MW 725.85, ALogP 1.57, HBA 9, HBD 7, PSA 211.08, QED 0.15
Compound (SMILES): Cc1cnc(-c2cc(Cl)ccc2F)cc1-n1c(=O)n(C)c2cnccc21
InChIKey: WWSVFSVYBGWGPQ-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: IC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 368.8, ALogP 3.89, HBA 5, HBD 0, PSA 52.71, QED 0.54
Compound (SMILES): Cc1cc(OCCCc2c3n(c4c(-c5c(C)nn(C)c5C)c(Cl)ccc24)C[C@@H](C)N(Cc2cccc(C(=O)O)c2)C3=O)cc(C)c1Cl
InChIKey: SBXXUMARFCZQCG-JOCHJYFZSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Fluorescence Polarization Anisotropy Competition Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using either a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) or a fluorescein isothiocyanate-labeled BH3 peptide derived from Bim (FITC-AHx-EARIAQELRRIGDEFNETYTR-NH2) that were purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 15 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). The Bim based assay was run with 1 nM FITC-Bim peptide and 1.5 nM recombinant Mcl-1 (residues 172-327) added to assay buffer (20 mM TRIS pH 7.5, 50 mM NaCl, 3 mM DTT, 0.01% CHAPS). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Î35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer.
Measurement: Ki < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 673.64, ALogP 8.34, HBA 6, HBD 1, PSA 89.59, QED 0.16
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC)C(C)C)C(N)=O
InChIKey: AVSZOFXNNDIXRT-LNEAKYCGSA-N
Target: Type-1 angiotensin II receptor A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25095
Assay: Agonist activity at rat AT1aR expressed in HEK293 cells incubated for 60 mins by luminescence based beta-arrestin recruitment assay
Measurement: EC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 1017.2
Compound (SMILES): CC[N@+]1(C[C@@H](CC(=O)[O-])c2cccc(-n3nc(C)cc3C)c2)CC[C@@H](CCc2ccc3c(n2)NCCC3)C1
InChIKey: ZHDLQWCRZPIIAQ-YXOCPYSXSA-N
Target: Integrin alpha-V/beta-8 (PROTEIN COMPLEX), Homo sapiens
UniProt: P26012
Assay: Inhibition of integrin alphavbeta8 (unknown origin) expressed in human K562 cells assessed as reduction in cell adhesion to GST-LAP1 (242 to 252 amino acids) incubated for 30 mins by fluorescent probe BCECF-AM based fluorescence assay
Measurement: IC50 = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 515.7, ALogP 3.96, HBA 6, HBD 1, PSA 82.87, QED 0.41
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)C2CC(=O)N(c3ccccc3)C2)cc1
InChIKey: NUJALWVOCRMDBE-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to recombinant human CA4 by DSF-based fluorescence thermal shift assay
Measurement: Kd = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 359.41, ALogP 1.33, HBA 4, HBD 2, PSA 109.57, QED 0.86
Compound (SMILES): Cc1nc2sc(C(=O)c3ccccc3)c(N)c2c(C)c1Cl
InChIKey: VXDNJGCGUCMVCS-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08485
Assay: Positive allosteric modulation activity at rat M4 receptor expressed in CHO cells co-expressing Gqi5 protein assessed as potentiation of EC20 acetyl choline-induced response by calcium mobilization assay
Measurement: EC50 = 692 nM (pChEMBL 6.159999847412109)
Descriptors: MW 316.81, ALogP 4.38, HBA 4, HBD 1, PSA 55.98, QED 0.71
Compound (SMILES): CC[C@H](Nc1ncnc2[nH]cnc12)c1nc2cccc(NCc3ccc(C(=O)NO)cc3)c2c(=O)n1-c1ccccc1
InChIKey: OLUMCBYQNVOFLW-NRFANRHFSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant full length human C-terminal His-tagged HDAC3 (1 to 428 residues) expressed in baculovirus infected insect cells using fluorogenic peptide p53 residues 379-382 (RHKK(Ac)AMC) as substrate measured after 1 to 2 hrs by fluorescence assay
Measurement: IC50 = 6699 nM (pChEMBL 5.170000076293945)
Descriptors: MW 561.61, ALogP 4.35, HBA 10, HBD 5, PSA 162.74, QED 0.13
Compound (SMILES): O=c1[nH]cnc2c(-n3cc(CCN4CCC(c5cc(CN6CCCC6)cc(C(F)(F)F)c5)CC4)cn3)nccc12
InChIKey: LAGKZFNQXIBSDJ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of KDM5B (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 551.62, ALogP 4.54, HBA 7, HBD 1, PSA 82.94, QED 0.36
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CC(C(=O)O)C(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(N)=O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N2
InChIKey: DJUPOXJVHQDKPZ-WWOYIMJESA-N
Target: Neuronal acetylcholine receptor; alpha3/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12390
Assay: Antagonist activity at rat alpha3beta2 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 = 16.6 nM (pChEMBL 7.78000020980835)
Descriptors: MW 1695.91
Compound (SMILES): Cc1cc(-n2cc(S(=O)(=O)C3COC3)c3ccc(N[C@@H](C)c4ccc(F)cn4)nc32)n[nH]1
InChIKey: NNWRFTLSEJKLQI-ZDUSSCGKSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of recombinant human ALK expressed in HEK293 cells assessed as reduction in ALK autophosphorylation at Tyr1604 residue incubated for 60 mins by sandwich ELISA
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 456.5, ALogP 2.94, HBA 8, HBD 2, PSA 114.79, QED 0.46
Compound (SMILES): Nc1c(C(=O)c2ccncc2)sc2nc(O)c3c(c12)CCCC3
InChIKey: PODWKHQMHGCPBB-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08485
Assay: Positive allosteric modulation activity at rat M4 receptor expressed in CHO cells co-expressing Gqi5 protein assessed as potentiation of EC20 acetyl choline-induced response by calcium mobilization assay
Measurement: EC50 = 182 nM (pChEMBL 6.739999771118164)
Descriptors: MW 325.39, ALogP 3.09, HBA 6, HBD 2, PSA 89.1, QED 0.71
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)NCc2cn(Cc3ccccc3Cl)nn2)C[C@H](N)[C@H]1NC(C)=O
InChIKey: GQWIOAKKIPNODP-YTFSRNRJSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: B4URF0
Assay: Inhibition of Influenza A virus H5N1 Neuraminidase N1 H274Y mutant preincubated for 10 mins followed by MUNANA substrate addition and measured after 40 mins by fluorescence method
Measurement: IC50 = 79200 nM (pChEMBL 4.099999904632568)
Descriptors: MW 489.02, ALogP 2.33, HBA 7, HBD 3, PSA 124.16, QED 0.47
Compound (SMILES): Cc1c(C(=O)N2CCC(C(C#N)CCF)CC2)cnn1-c1nc2c(c(=O)[nH]1)CCC2
InChIKey: VMTGXJKDZZQHFZ-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 412.47, ALogP 2.1, HBA 6, HBD 1, PSA 107.67, QED 0.81
Compound (SMILES): CN1CCC(CNc2cc(Cl)nn3c(-c4cc(F)c5[nH]c(Nc6ccccc6)nc5c4)cnc23)CC1
InChIKey: KCNZTRADVNKNEF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Inhibition of dephosphorylated IRE1alpha (G547 to L977 residues) (unknown origin) autophosphorylation at S724 after 25 mins in presence of ATP by dissociation-enhanced lanthanide fluorescence immunoassay
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 505, ALogP 5.56, HBA 7, HBD 3, PSA 86.17, QED 0.28
Compound (SMILES): N=C(N)N(CCCCN1CCN(CCCCCCCOc2ccccc2)CC1)Cc1ccc(Cl)cc1
InChIKey: SNDDKBQSRRYOPO-UHFFFAOYSA-N
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: Displacement of [3H]-Nalpha-Methylhistamine from human recombinant histamine H4 receptor expressed in CHO cell membranes after 1 hrs by liquid scintillation counting analysis
Measurement: Ki = 1071.52 nM (pChEMBL 5.96999979019165)
Descriptors: MW 514.16, ALogP 5.46, HBA 4, HBD 2, PSA 68.82, QED 0.18
Compound (SMILES): CC(=O)N(C)C1CCCN(Cc2cc3nc(-c4cccc5[nH]ccc45)nc(N4CCOCC4)c3s2)C1
InChIKey: QUKLSGWBYFZZDT-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using biotin-PIP3 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence polarization assay
Measurement: IC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 504.66, ALogP 4.12, HBA 7, HBD 1, PSA 77.59, QED 0.44
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@@H]1CCN(C(=O)c2ccccc2)c2ccc(Cc3ccc4ccccc4c3)cc21.O=C(O)C(F)(F)F
InChIKey: VULIIEAMIXSIKT-PFHIRXQESA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]diprenorphine from human kappa opioid receptor expressed in CHO cell membranes measured after 1 hr by liquid scintillation counting method
Measurement: Ki = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 583.73, ALogP 6.53, HBA 4, HBD 3, PSA 95.66, QED 0.2
Compound (SMILES): CC1(Cc2nnc(C(c3nc4ccc(-c5ccc(C(=O)N6CCOCC6)cc5)cc4s3)S(C)(=O)=O)o2)NC(=O)NC1=O
InChIKey: PSAXVSMUHPDPLQ-UHFFFAOYSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition of endothelial lipase in human HT1080 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins in presence of human serum by fluorescence assay
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 610.67, ALogP 2.09, HBA 11, HBD 2, PSA 173.69, QED 0.3
Compound (SMILES): CC1(C(=O)O)CCCN(c2ccc(-c3ccc(-c4nc5cc(Cl)ccc5[nH]4)cn3)cn2)C1
InChIKey: PRAHLUQGPUBTRW-UHFFFAOYSA-N
Target: Sterol O-acyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35610
Assay: Inhibition of human ACAT1
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 447.93, ALogP 5.03, HBA 5, HBD 2, PSA 95, QED 0.46
Compound (SMILES): CN(C)C(=O)c1cnc(Nc2ccc(F)cn2)cc1Nc1ccccc1C(N)=O
InChIKey: YWUIKGIJIWMCCI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 JH1 domain (unknown origin)
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 394.41, ALogP 2.9, HBA 6, HBD 3, PSA 113.24, QED 0.59
Compound (SMILES): C=CC(=O)Nc1cc(Nc2nccc(Nc3ccccc3S(=O)(=O)C(C)C)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: ZCICFBOTBSKMJF-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type GST-tagged human EGFR cytoplasmic domain (668 to 1210 residues) expressed in baculovirus expression system using Poly G:T (4:1) as substrate after 30 mins by Z-LYTE assay
Measurement: IC50 = 2480 nM (pChEMBL 5.610000133514404)
Descriptors: MW 567.72, ALogP 4.28, HBA 10, HBD 3, PSA 128.79, QED 0.26
Compound (SMILES): O=C(NCc1ncccc1F)c1nc(C2(O)CN(CCc3nc4ccccc4[nH]3)C2)sc1Cl
InChIKey: MBIZYXHDGGUFFZ-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Binding affinity to C-terminal FLAG-tagged human ferroportin expressed in Pichia pastoris assessed as reduction in inhibition of binding of TMR-hepcidin to Fpn incubated for 90 mins by fluorescence polarization assay
Measurement: IC50 = 154 nM (pChEMBL 6.809999942779541)
Descriptors: MW 486.96, ALogP 2.88, HBA 7, HBD 3, PSA 107.03, QED 0.37
Compound (SMILES): CC(=O)NCCNCc1cc(C)c(OCc2cccc(-c3ccccc3)c2C)cc1OCc1cncc(C#N)c1
InChIKey: RGUPKQRLKVPKIF-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of human PD1 stably expressed in human Jurkat T cells co-expressing NFAT-induced luciferase/human PDL1 stably expressed in CHOK1 cells co-expressing aAPC protein-protein interaction assessed as increase in NFAT signaling measured after 6 hrs by bio-glo luciferase reporter gene assay
Measurement: EC50 = 3002 nM (pChEMBL 5.519999980926514)
Descriptors: MW 534.66, ALogP 5.62, HBA 6, HBD 2, PSA 96.27, QED 0.23
Compound (SMILES): CC1(C)OC2(CCN(CCc3ccccc3)CC2)CN(c2ccccc2)C1=O
InChIKey: FVBRGBXYCPMCNB-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H]-(+)-pentazocine from human sigma-1 receptor expressed in HEK293 membranes incubated for 120 mins by liquid scintillation counting method
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 378.52, ALogP 3.91, HBA 3, HBD 0, PSA 32.78, QED 0.81
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc3c(c2)COc2cc4c(ccc5nc([C@@H]6CCCN6C(=O)[C@H](NC(=O)OC)c6ccccc6)[nH]c54)cc2-3)[nH]1)C(C)C
InChIKey: UVDRNMFWRGJGIM-HXSJKTFTSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A L31M mutant in HCV genotype 2a J6 (M31) infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.134 nM (pChEMBL 9.869999885559082)
Descriptors: MW 824.94, ALogP 7.47, HBA 9, HBD 4, PSA 183.87, QED 0.11
Compound (SMILES): COc1ccc(CCN(C(=O)OC2CCN(C)CC2)c2ccccc2)cc1OC
InChIKey: KYIAOTGZEXVAKQ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human M5 AChR expressed in CHO cell membranes after 1 to 2 hrs by liquid scintillation spectrometry method
Measurement: Ki = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 398.5, ALogP 3.98, HBA 5, HBD 0, PSA 51.24, QED 0.71
Compound (SMILES): O=C(Nc1cc(COCc2cn(CCNc3c4c(nc5ccccc35)CCCC4)nn2)ccn1)Nc1cccc2c1C1CCCCN1C2=O
InChIKey: IDMGTGWKKYHBFA-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human recombinant AChE using ATCh as substrate preincubated for 20 mins followed by substrate addition and measured for 3 mins by Ellman method
Measurement: IC50 = 20.8 nM (pChEMBL 7.679999828338623)
Descriptors: MW 657.78, ALogP 6.25, HBA 9, HBD 3, PSA 139.19, QED 0.16
Compound (SMILES): CCCCCn1cc(C(=O)c2cccc3ccccc23)c2cccc(F)c21
InChIKey: NIFGXRPARMHXLK-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at human CB1R expressed in CHO cells by Ca2+ flux assay
Measurement: EC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 359.44, ALogP 6.35, HBA 2, HBD 0, PSA 22, QED 0.29
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)C(C)C)[C@@H](C)O)C(C)C)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)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)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: WYDXKHQWOGJCGC-SVIYQQATSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Agonist activity at human calcitonin receptor expressed in BHK570 cells assessed as increase in intracellular cAMP concentration incubated for 3 hrs in presence of 10% FBS by CRE luciferase reporter gene assay
Measurement: EC50 = 0.011 nM (pChEMBL 10.960000038146973)
Descriptors: MW 3648.13
Compound (SMILES): O=C(CCCCCO)N[C@@H](CC(=O)N1CCn2c(nnc2C(F)(F)F)C1)Cc1cc(F)c(F)cc1F
InChIKey: QLMONPUKNJSOOT-CQSZACIVSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of human DPP-4 using Ala-Pro-AMC as substrate preincubated for 10 mins followed by substrate addition and measured after 5 to 10 mins by fluorescence assay
Measurement: IC50 = 223 nM (pChEMBL 6.650000095367432)
Descriptors: MW 521.46, ALogP 2.73, HBA 6, HBD 2, PSA 100.35, QED 0.28
Compound (SMILES): COCCCN(C(=O)CCl)c1nc(-c2ccc(OC)cc2)cs1
InChIKey: KZMAWJRXKGLWGS-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BLA8
Assay: Agonist activity at mouse TRPA1 expressed in HEK293T cells by whole cell patch clamp recordings
Measurement: EC50 = 5260 nM (pChEMBL 5.28000020980835)
Descriptors: MW 354.86, ALogP 3.43, HBA 5, HBD 0, PSA 51.66, QED 0.54
Compound (SMILES): CNc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCN(C)CC4)cc3)sc2n1
InChIKey: GKRFDYFVDMFALN-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 424.57, ALogP 2.64, HBA 7, HBD 3, PSA 86.52, QED 0.56
Compound (SMILES): O=C(Nc1ccc(Oc2ncnc3cc(OCCCN4CCOCC4)c4c(c23)OCCO4)c(F)c1)Nc1cc(C(F)(F)F)ccc1F
InChIKey: YBXDKOSIYONZOF-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Test of Small Molecule Compounds for Inhibiting the Activity of C-RAF and B-RAF Kinases: 1. Preparation of test compounds: according to the molecular weight of the compounds, an appropriate volume of DMSO was directly added to dissolve the test compounds. For storing the compound, the concentration of DMSO is 100%, and the final concentration of DMSO in the experimental system is 1%. The compounds were 3-fold serially diluted with DMSO to obtain a total of 8 dilutions, with a maximum concentration of 1000 nM and a minimum concentration of 0.46 nM.2. Preparation of the sorafenib positive control: sorafenib, a selective inhibitor of BRAF and RAF1, was used as the positive control of this experiment, and the dilution method thereof was the same as that of the above test compounds.3. Test Conditions:Enzyme: B-RAF: 0.1 ng/l (the final concentration in the reaction system); C-RAF: 0.1 ng/μl (the final concentration in the reaction system)Substrate and ATP: inactive MEKI: 2 ng/μl (the final concentration in the reaction system); ATP: 35 μM (the final concentration in the reaction system)HPE: the reaction without enzyme (1% DMSO)ZPE: the reaction with enzyme but without compound (1% DMSO)4. Test procedure:a) 1 ul of 10-fold diluted compound or 10% DMSO was added to a 384-well assay plate,b) 4 ul enzyme solution or assay buffer was added to the wells of the assay plate,c) the plate was centrifuged at 1000 rpm for 1 minute to homogeneous,d) 5 ul of ATP-substrate mixture was added to the wells of the assay plate,e) the plate was shaked for mixing for 2 minutes,f) the plate was incubated at 30° C. for 1 hour,g) 10 ul of ADP-Glo reagent was added to the wells of the assay plate, and the plate was incubated for 40 minutes at 27° C.,h) 20 ul of kinase assay solution was added to the wells of the plate, and the plate was incubated for 30 minutes at 27° C.,i) the chemiluminescent signal was read with Envision.5. Analysis of the results: calculation of the compound inhibition rate:Inhibition rate (%)=(control measurement without compound−sample measurement)/(control measurement without compound−control measurement without enzyme)*100%The IC50 values of the positive control compound and the test compounds were calculated using the Prism software according to the variable slope of the curve.
Measurement: IC50 = 2750 nM (pChEMBL 5.559999942779541)
Descriptors: MW 661.58, ALogP 6.24, HBA 9, HBD 2, PSA 116.3, QED 0.16
Compound (SMILES): O=C(O)CNC(=O)c1c(O)c2c(n(Cc3ncc(C(F)(F)F)cn3)c1=O)COC2
InChIKey: KFPNYIUHMRAXPA-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KS0
Assay: Inhibition of recombinant human HIF-PHD1 expressed in baculovirus-infected Sf9 cells using biotin labelled DLDLEMLAPYIPMDDDFQL and 2-oxoglutarate as substrates preincubated for 30 mins followed by substrates addition and measured after 2 hrs by TR-FRET assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 414.3, ALogP 0.26, HBA 8, HBD 3, PSA 143.64, QED 0.63
Compound (SMILES): CCN(CCCNC(=O)c1cc(O)c(C(=O)NCCCN(CC)Cc2ccccc2)cc1O)Cc1ccccc1
InChIKey: UTALNRZOLLLNFR-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate after 15 mins by Ellman's method
Measurement: IC50 = 26800 nM (pChEMBL 4.570000171661377)
Descriptors: MW 546.71, ALogP 4.38, HBA 6, HBD 4, PSA 105.14, QED 0.16
Compound (SMILES): N#CNc1ccc(CNc2cc(Nc3ccc(N4CCOCC4)cc3)ncn2)cc1
InChIKey: IPBAWSDNKDTYNA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and further incubated for 30 mins and subsequently measured after 1 hr by HTRF assay
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 401.47, ALogP 3.56, HBA 8, HBD 3, PSA 98.13, QED 0.41
Compound (SMILES): Cc1cccc(C)c1OCC(=O)N[C@@H](Cc1ccccc1)[C@H](O)C(=O)N1CSC(C)(C)[C@@H]1C(=O)N[C@H]1c2ccccc2C[C@H]1O
InChIKey: KKTYZYHUPKXLPL-JNDSVOFMSA-N
Target: Plasmepsin 4 (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q17SB2
Assay: Inhibition of recombinant Plasmodium falciparum Plasmepsin 4
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 631.8, ALogP 3.23, HBA 7, HBD 4, PSA 128.2, QED 0.27
Compound (SMILES): S=C1Sc2cccc(Cl)c2C2=NCCCN12
InChIKey: XOTIQYGBONSIAZ-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human C-terminal His-tagged HDAC3 (1 to 428 residues) expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 26000 nM (pChEMBL 4.579999923706055)
Descriptors: MW 268.79, ALogP 3.18, HBA 3, HBD 0, PSA 15.6, QED 0.67
Compound (SMILES): CCS(=O)(=O)Nc1cc(-c2ccc(O)c(F)c2)cc2[nH]ncc12
InChIKey: PQUWBTQUHMDJRP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human His-tagged JAK2 expressed in baculovirus using biotin-synthetic peptide as substrate after 20 mins by HTRF assay
Measurement: IC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 335.36, ALogP 2.84, HBA 4, HBD 3, PSA 95.08, QED 0.68
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCN(CCCn2ccnc2)C3)n(C)c1=O
InChIKey: OGVPGWMXQKIVIK-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Displacement of [3H]CCPA from A1 receptor in rat brain cortex membranes by liquid scintillation counting method
Measurement: Ki > 1500 nM (pChEMBL 5.823999881744385)
Descriptors: MW 343.39, ALogP -0.46, HBA 9, HBD 0, PSA 82.88, QED 0.64
Compound (SMILES): C=CC(=O)Nc1ccc(Nc2ncnc3cc(OC)c(OCCN4CCOCC4)cc23)cc1
InChIKey: VHCZHJHCTYDXLJ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR T790M mutant (unknown origin)
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 449.51, ALogP 3.22, HBA 8, HBD 2, PSA 97.84, QED 0.48
Compound (SMILES): CNC(=O)c1c(-c2ccccc2)c([C@H](C)Nc2ncnc(N)c2C#N)nc2ccc(F)cc12
InChIKey: DVAFBEJPVBOYJN-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of polyHis tagged full length recombinant PI3Kdelta (unknown origin) expressed in Sf9 cells co-expressing p85 incubated for 20 mins by alpha screen assay
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 441.47, ALogP 3.82, HBA 7, HBD 3, PSA 129.61, QED 0.43
Compound (SMILES): C[C@@H](N)c1cccc(-c2cccc(COc3ccccc3CC(=O)O)c2)c1
InChIKey: MSYFKYPXROEHAC-MRXNPFEDSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition of F11a (unknown origin)
Measurement: IC50 = 5200 nM (pChEMBL 5.28000020980835)
Descriptors: MW 361.44, ALogP 4.58, HBA 3, HBD 2, PSA 72.55, QED 0.65
Compound (SMILES): O=c1nc(-c2ccccn2)sc2ccccc12
InChIKey: GBAKVEWPYUIGHN-UHFFFAOYSA-N
Target: Macrophage migration inhibitory factor (SINGLE PROTEIN), Homo sapiens
UniProt: P14174
Assay: Binding affinity to recombinant human C-terminal His-tagged MIF expressed in Escherichia coli BL21 (DE3) at 400 nM incubated for 6 hrs using labelled compound by scintillation proximity assay
Measurement: Kd = 157 nM (pChEMBL 6.800000190734863)
Descriptors: MW 240.29, ALogP 2.72, HBA 4, HBD 0, PSA 42.85, QED 0.66
Compound (SMILES): O=C([S-])N1CCN(c2ccc(C(F)(F)F)cc2)CC1.[Na+]
InChIKey: OPBYPLLCHQENHU-UHFFFAOYSA-M
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 catalytic domain preincubated for 15 mins by CO2 hydration stopped-flow assay
Measurement: Ki = 11.8 nM (pChEMBL 7.929999828338623)
Descriptors: MW 290.31, ALogP 2.88, HBA 2, HBD 1, PSA 23.55, QED 0.8
Compound (SMILES): Cn1cncc1-c1c[nH]c2ccc(F)c(F)c12
InChIKey: TXEGQJZDEZKANQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H] LSD from human recombinant 5-HT6 receptor expressed in HEK293 cells measured after 1 hr by microbeta scintillation counting method
Measurement: Ki = 603 nM (pChEMBL 6.21999979019165)
Descriptors: MW 233.22, ALogP 2.85, HBA 2, HBD 1, PSA 33.61, QED 0.69
Compound (SMILES): N#Cc1nc2c(nc1N)-c1ccccc1C2=O
InChIKey: RCHPGNATOYICNX-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P40818
Assay: Inhibition of human USP8 using Ub-AMC as substrate
Measurement: IC50 = 48000 nM (pChEMBL 4.320000171661377)
Descriptors: MW 222.21, ALogP 1.14, HBA 5, HBD 1, PSA 92.66, QED 0.62
Compound (SMILES): NCc1ccc(S(=O)(=O)c2ccc(S(=O)(=O)c3ccccc3)cc2)s1
InChIKey: WIVVLFLIKNOLCR-UHFFFAOYSA-N
Target: Protein-lysine 6-oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P28300
Assay: LOX Enzyme Activity Assay: The following reagents were prepared:Reagents500 mM CHES, pH 9 (with NaOH), filtered (MW=207.29)20.7 g in 200 ml in dH2O10% Pluronic F-127 (store at 4° C.)1 g in 10 ml in dH2O10 % BSA (store at 4° C.)−2.5 g in 25 ml dH2O1 M MgCl2.6H2O (MW=203)5.1 g in 25 ml dH2O5 M Urea (MW=60.06)60 g in 200 ml dH2O5 M NaCl (MW=58.44)14.6 g in 50 ml dH2O8.5 M Cadaverine Dihydrochloride (MW=175.10): Sigma, Cat No: C85611.49 g in 1 ml dH2O10 mM Na3VO4, pH 10 (with HCl), boil to activate (MW=183.91): Sigma, Cat No: S65080.1839 g in 10 ml dH2O20 mM Amplex Red (MW=257.25): Invitrogen, Cat No: A12222.5 mg in 1 ml DMSO (aliquot into 40 μl and store at −20° C.)1000 U/ml HRP in dH2O (store at 4° C.): Sigma, Cat No: P2088H2O2 (store at 4° C.): Sigma, Cat No: H1009DMSOLOX Assay Buffer: Volume (μl) Reagent 1 × plate Final Concn 500 mM CHES, pH 9 5000 100 mM 10% Pluronic F-127 125 0.05% 10% BSA 1250 0.5% 1M MgCl2 25  1 mM 5M Urea 5000 1M 5M NaCl 500 100 mM dH2O 13100 — Total Volume 25 000 —Inhibitors (Test Compounds):10 mM stock diluted to 10, 3, 1, 0.3, 0.1, 0.03, 0.01, 0.003, 0.001, and 0.0003 mM in drug plate, resulting in a concentration of 100, 30, 10, 3, 1, 0.3, 0.1, 0.03, 0.01, and 0.003 uM in the assay.LOX enzyme:LOX enzyme was obtained from pig skin by the method of Shackleton et al 1990.Assay Plates:Black, flat bottom 96 well platesProcedure:1. Dilute LOX enzyme in Assay Buffer (˜4 ml for one plate, 8 ml for two plates) (dilution dependent on batch activity)2. Add 0.5 μl test compound serial dilutions, in duplicate3. Add 0.5 μl serial dilutions of positive control, BAPN, down column 11 (no duplication)4. Add following controls: 0.5 μl DMSO (100% activity control)5. Cover plate and incubate for 20 min at room temperature on a plate shaker6. Prepare Start Mix: Volume Reagent 1 × plate 2 × plate Final Concn Assay Buffer 2 ml 3 ml — 8.5M Cadaverine 23 μl 34.5 μl 97.8 mM 20 mM Amplex Red 10 μl 15 μl 100 μM 1000 U/ml HRP 10 μl 15 μl 5 U/ml7. Add 10 μl Start Mix to No HRP control wells8. Add HRP to the Start Mix. Add 10 ul to all wells EXCEPT No HRP control wells9. Incubate for 45 min at room temp on a plate shaker, protected from light10. Measure fluorescence using a plate reader: Excitation wavelength: 545 nm Emission wavelength: 585 nm HRP Counter Assay Protocol1. Dilute 5 μl H2O2 in 640 μl dH2O. Add 1 μl diluted H2O2 to 10 ml Assay Buffer. Vortex2. Add 40 μl H2O2+Assay Buffer into every well on the counter assay plate EXCEPT no H2O2 control wells (add 40 μl Assay Buffer only)3. Add 0.5 μl test compound serial dilutions, in duplicate4. Add 0.5 μl serial dilutions of positive control, Na3VO4, down column 11 (no duplication)5. Add following controls: 0.5 μl DMSO (100% activity control) 1 μl diluted H2O2 (blow out control)6. Incubate for 20 min at room temp on a plate shaker.
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 393.51, ALogP 2.87, HBA 6, HBD 1, PSA 94.3, QED 0.72
Compound (SMILES): O=C(Nc1n[nH]c2cc(-c3cccc(NS(=O)(=O)C4CC4)c3)ccc12)C1CC1
InChIKey: HJDMEPOCEJXNJU-UHFFFAOYSA-N
Target: BMP-2-inducible protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NSY1
Assay: Displacement of Alexafluor labelled kinase tracer236 from biotinylated C-terminal Avi-tagged BMP2K kinase domain (38 to 345 residues) (unknown origin) expressed in Escherichia coli measured after 1.5 hrs by TR-FRET assay
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 396.47, ALogP 3.48, HBA 4, HBD 3, PSA 103.95, QED 0.59
Compound (SMILES): Cl.NOC(c1ccc(F)cc1)c1ccc(F)cc1
InChIKey: JCKSWNFJWVXHBU-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells using L-tryptophan as substrate after 20 hrs
Measurement: IC50 = 1680 nM (pChEMBL 5.78000020980835)
Descriptors: MW 235.23, ALogP 2.94, HBA 2, HBD 1, PSA 35.25, QED 0.83
Compound (SMILES): CS(=O)(=O)c1ccc(Oc2cc(F)cc(C#N)c2)c2c1[C@H](O)[C@H](F)[C@H]2F
InChIKey: LOMMPXLFBTZENJ-BBWFWOEESA-N
Target: Endothelial PAS domain-containing protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99814
Assay: Scintillation Proximity Assay (SPA): HIF-2a: The total assay volume was about 100 uL in the following configuration: 2 uL compound in 100% DMSO, 88 uL buffer with protein and probe and 10 uL of SPA beads. The compound was diluted in a master plate consisting of a 10-point dose response with a 3-fold compound dilution from 100 nM to 5 nM. Assays were run on a 96-well plate in which one column, designated as the high signal control, contained DMSO with no compound and another column, designated as the low signal control, contained no protein. Prior to plating out of compound, a buffer solution, consisting of 25 mM TRIS pH 7.5 (Sigma), 150 mM NaCl (Sigma), 15% Glycerol (Sigma), 0.15% BSA (Sigma), 0.001% Tween-20 (Sigma), 150 nM Compound 183 and 100 nM HIF-2Î± HIS TAG-PASB Domain, was made and allowed to equilibrate for 30 minutes. Compounds that were to be tested were then plated in to a 96-well white clear bottom Isoplate-96 SPA plate (Perkin Elmer). To the compounds, 88 uL of the buffer solution was then added, the plate was covered with a plastic cover and then aluminum foil, placed onto a shaker and equilibrated for 1 hour. After equilibration, 10 uL of a 2 mg/mL solution of YSi Cu His tagged SPA beads (Perkin Elmer) were then added to each well of the plate, covered and equilibrated for another 2 hours. The plates were then removed from the shaker, placed into a 1450 LSC and luminescence counter MicroBeta Trilux (Perkin Elmer) to measure the extent of probe displacement.
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 383.35, ALogP 3.29, HBA 5, HBD 1, PSA 87.39, QED 0.88
Compound (SMILES): CNC1=N[C@@H]2C[C@H](O)[C@@H](CO)O[C@@H]2S1
InChIKey: UMXYJFMLLLIFPW-XZBKPIIZSA-N
Target: Protein O-GlcNAcase (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8VIJ5
Assay: Inhibition of OGA in rat PC12 cells assessed as OGlcNAcylated protein level incubated for 24 hrs by ELISA
Measurement: EC50 = 33.1 nM (pChEMBL 7.480000019073486)
Descriptors: MW 218.28, ALogP -0.85, HBA 6, HBD 3, PSA 74.08, QED 0.53
Compound (SMILES): O=C(CCCN1CCCN(c2ncccn2)CC1)c1ccc(F)cc1
InChIKey: GUOJTYBMIRVPKO-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement [3H]-Pentazocine from sigma 1 receptor (unknown origin) expressed in HEK cell membranes
Measurement: Ki = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 342.42, ALogP 2.79, HBA 5, HBD 0, PSA 49.33, QED 0.76
Compound (SMILES): O=C(O)c1ccc2c(c1)CCCC(c1ccccc1Cl)=C2c1ccc(O[C@H]2CCN(CCCF)C2)cc1
InChIKey: XOVGWMBSIUWRAG-VWLOTQADSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Estrogen Receptor Coactivator Assay: It is a competition assay, where binding of a test compound to a complex comprised of (i) His6-ERα298-554 protein representing ERα ligand-binding domain, (ii) Tb-labeled His6 antibody, (iii) a fluorescein-labeled PGC1α coactivator peptide (EAEEPSLLKKLLLAPANTQ), and (iv) estradiol, results in a decrease of the TR-FRET signal due to dissociation of the coactivator peptide. His6-ERα298-554 proteins were expressed as WT or D538G or Y537S mutants in E. coli and purified by affinity chromatography. The assay works in a homogeneous mix-and-read format. In a typical experiment, a 4 μL mixture of 0.5 nM His6-ERα298-554, 0.5 nM Tb-labeled His6 antibody, 250 nM PGC1a peptide, and 3 nM estradiol in 100 mM potassium phosphate, pH 7.4, 0.01% Tween-20, 0.02% NaN3, 5 mM DTT, was added to 40 nL test compound in DMSO and incubated overnight at room temperature. The TR-FRET 520:495 nm emission ratio was calculated and used to determine the IC50 value from a dose response curve fit to the 4-parameter logistic equation. The antagonist activity with respect to estrogen receptors in this test is given by the concentration which inhibits 50% of the estrogen receptor activity (or IC50) in nM.
Measurement: IC50 = 618 nM (pChEMBL 6.210000038146973)
Descriptors: MW 520.04, ALogP 7.15, HBA 3, HBD 1, PSA 49.77, QED 0.34
Compound (SMILES): N#Cc1ccc(-c2csc(N3N=C(c4ccc(N5CCOCC5)cc4)CC3c3ccc(Cl)cc3)n2)cc1
InChIKey: MFRSLBCAYUHKEI-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15303
Assay: Inhibition of recombinant human N-terminal GST-tagged HER4 (682 to 993 residues) expressed in baculovirus infected Sf9 insect cells using Poly (4:1 Glu, Tyr) peptide as substrate incubated for 1 hr by ADP-Glo assay
Measurement: IC50 = 4680 nM (pChEMBL 5.329999923706055)
Descriptors: MW 526.07, ALogP 6.53, HBA 7, HBD 0, PSA 64.75, QED 0.3
Compound (SMILES): CC(C)(C)C(=O)Nc1ccc2c(-c3ccccc3)ccnc2c1O
InChIKey: LGYGXRFUBXECRS-UHFFFAOYSA-N
Target: DNA topoisomerase 2-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P11388
Assay: Inhibition of topoisomerase 2alpha in human SW620 organoids transfected with EcadPro-RFP reporter assessed as reversion of epithelial-mesenchymal transition by measuring increase in E-cadherin expression after 72 hrs by Hoechst 33342 staining based mCherryRFP reporter gene assay
Measurement: EC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 320.39, ALogP 4.59, HBA 3, HBD 2, PSA 62.22, QED 0.68
Compound (SMILES): CC(C)NC[C@H](O)COc1ccccc1CCCn1cc(CNCc2cn(CCCc3ccccc3OC[C@@H](O)CNC(C)C)nn2)nn1
InChIKey: NBTZMFMFCAFRPY-HEVIKAOCSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Displacement of [3H]DHA from beta1 adrenergic receptor (unknown origin) stably expressed in HEK293 cell membranes measured after 90 mins by scintillation counting analysis
Measurement: Ki = 1.096 nM (pChEMBL 8.960000038146973)
Descriptors: MW 677.9, ALogP 2.9, HBA 13, HBD 5, PSA 156.43, QED 0.07
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC(=O)O)c2)o1)[C@@H](CC)N(C=O)OC(=O)c1ccccc1C(C)C
InChIKey: HCWOWZJNPLCQNU-CCNCKIRNSA-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 808.84, ALogP 4.2, HBA 11, HBD 6, PSA 268.18, QED 0.03
Compound (SMILES): COCC#C[C@]1(O)CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3[C@@H](c3ccc(N(C)C)cc3)C[C@@]21C
InChIKey: NAGHPXVIWRQPIX-BLZQOCCISA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Antagonist activity at human progesterone receptor expressed in CHO-K1 cells harboring firefly luciferase gene after 20 hrs by One-Glo luciferase reporter gene assay
Measurement: IC50 = 4242 nM (pChEMBL 5.369999885559082)
Descriptors: MW 475.67, ALogP 5.36, HBA 4, HBD 1, PSA 49.77, QED 0.6
Compound (SMILES): CC(C)(C)S(=O)(=O)c1cc2c(Nc3ccc4scnc4c3)ncnc2cc1OCCO
InChIKey: UHDOJINBFLDQJM-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: G3V783
Assay: Inhibition of fluorescent-labelled ligand binding to rat RIP2K preincubated for 10 mins followed by fluorescent-labelled ligand addition and measured after 10 mins by fluorescence polarization assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 458.57, ALogP 3.93, HBA 9, HBD 2, PSA 114.3, QED 0.45
Compound (SMILES): CN1C(=O)/C(=N\Nc2ccc(S(N)(=O)=O)cc2)c2ccccc21
InChIKey: XTNNORMRVRBNIN-JXAWBTAJSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 19.1 nM (pChEMBL 7.71999979019165)
Descriptors: MW 330.37, ALogP 1.13, HBA 5, HBD 2, PSA 104.86, QED 0.82
Compound (SMILES): COc1ccc(F)cc1C1CC1CN(C)CCCSc1nnc(-c2ccccc2)n1C.Cl
InChIKey: WPBGQWOUJGQJTR-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from recombinant human D4 receptor stably expressed in HEK cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 85.1 nM (pChEMBL 7.070000171661377)
Descriptors: MW 440.59, ALogP 4.85, HBA 6, HBD 0, PSA 43.18, QED 0.33
Compound (SMILES): Cc1cc(-c2nc3sc4c(c3c(=O)[nH]2)CCN(C)C4)cc(C)c1OCCCCCC(=O)NO
InChIKey: BBFKONWWIAFKEJ-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of HDAC7 (unknown origin) using biotinylated histone H3 KAc peptide (1 to 21 residues) as substrate by HTRF assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 470.6, ALogP 3.7, HBA 7, HBD 3, PSA 107.55, QED 0.26
Compound (SMILES): C#CCOc1ccc(/C=N/Cc2ccc(S(N)(=O)=O)cc2)cc1OC
InChIKey: JLWBKVGGJRNENA-DEDYPNTBSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human carbonic anhydrase 1 incubated for 10 mins prior to testing measured for 5 to 10 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 358.42, ALogP 1.97, HBA 5, HBD 1, PSA 90.98, QED 0.61
Compound (SMILES): C[C@@H]1C(=O)N/C(=C\c2ccccc2)c2nc3c(O)cccc3c(=O)n21
InChIKey: JKOZPSNPSQBQCF-UXEDPAHQSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of recombinant human SHP2 expressed in Escherichia coli using pNPP as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 333.35, ALogP 2.29, HBA 5, HBD 2, PSA 84.22, QED 0.72
Compound (SMILES): COc1ccc(-c2cccc(Nc3cc(=O)n(O)c(=O)n3C)c2)c(OC)c1
InChIKey: MZRNYYBXGJIEKS-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of re-constituted HIV1 reverse transcriptase RNase H domain fragment
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 369.38, ALogP 2.21, HBA 8, HBD 2, PSA 94.72, QED 0.67
Compound (SMILES): CC(C)CN1CCC(NC(=O)Cc2nc3cnc4[nH]ccc4c3n2[C@H]2CC[C@H](CC#N)CC2)CC1
InChIKey: SFRSQEVTJXTTHI-XUTJKUGGSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3-JH1/JH2 domain (512 to 1124 residues) (unknown origin) pre-incubated before NH2-KGGEEEEYFELVKK-CO2 substrate addition and measured after 45 mins by MS analysis
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 475.64, ALogP 4.34, HBA 6, HBD 2, PSA 102.63, QED 0.53
Compound (SMILES): C[C@H]1CCCOc2ccccc2C(=O)Nc2cccc(n2)-c2nncn21
InChIKey: LZTAURWQYWWPLU-ZDUSSCGKSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: TR-FRET Assay: Table 2: Alternatively, the protein kinase activity of the compounds described herein were tested using the ASK1/MAP3K5 assay by Reaction Biology Corp. The assay procedure can be found on Reaction Biology Corp.website at http://www.reactionbiology.com/webapps/site/KinasePDFs/ASK1_MAP3K5.pdf. ASK1/MAP3K5 was used as the protein kinase and 20 μM of myelin basic protein (MBP) and 10 μM ATP were used as the substrate.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 349.39, ALogP 3.33, HBA 6, HBD 1, PSA 81.93, QED 0.67
Compound (SMILES): CC(C)(C)Oc1cc(S(C)(=O)=O)cc(S(=O)(=O)c2ccc(CN)s2)c1
InChIKey: MAYGEFZADXBJTC-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB expressed in baculovirus infected BTI insect cells incubated for 1 hr by luminescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 403.55, ALogP 2.62, HBA 7, HBD 1, PSA 103.53, QED 0.82