lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(Nc1ccc(F)cc1-c1cc(Cl)cc(Cl)c1)OCC1CCNCC1
InChIKey: FDGDUTRHLLBSNR-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M2 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method
Measurement: Ki = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 397.28, ALogP 5.35, HBA 3, HBD 2, PSA 50.36, QED 0.73
Compound (SMILES): CC(=O)OCCC(/C=C/C=C/C#CC#C/C=C/CO)OC(=O)C=C(C)C
InChIKey: CQDVFBMTEZFKKY-JPSRSCNUSA-N
Target: Sterol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75908
Assay: Inhibition of human SOAT2-mediated [14C]Cholesterol ester synthesis in CHO cells after 6 hrs in presence of [14C]Oleic acid by TLC analysis
Measurement: IC50 = 36200 nM (pChEMBL 4.440000057220459)
Descriptors: MW 356.42, ALogP 2.49, HBA 5, HBD 1, PSA 72.83, QED 0.31
Compound (SMILES): CN[C@@H](C)C(=O)N[C@H](C(=O)N1C[C@@H](NC(=O)CCCCCCCN2CCN(c3ccc(Nc4ncc5c(C)c(C(C)=O)c(=O)n(C6CCCC6)c5n4)nc3)CC2)C[C@H]1C(=O)Nc1c(F)cccc1F)C(C)(C)C
InChIKey: OUTLYXINOACMSY-OYTRKBTESA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of human CDK6/cyclin-D3 using RB protein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 1011.23
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(SCCCN4CCOCC4)cc3)nc3ccsc23)c1
InChIKey: RVRZWPSRZFJAPX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) by ADP-Glo kinase assay
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 547.71, ALogP 6.17, HBA 9, HBD 2, PSA 88.61, QED 0.13
Compound (SMILES): C[N+](C)(C)C[C@@H]1COC[C@@H](c2ccc(Sc3ccccc3)cc2)O1.[I-]
InChIKey: KGZLPPBFBULZNG-XLCHORMMSA-M
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M2 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 194.98 nM (pChEMBL 6.710000038146973)
Descriptors: MW 344.5, ALogP 4, HBA 3, HBD 0, PSA 18.46, QED 0.76
Compound (SMILES): CN(C)CCCCCSC1=Nc2ccccc2C(CC(=O)NCc2ccc(F)cc2)N1c1ccc(-c2ccccc2)cc1
InChIKey: DOCPLAPSOWUOSM-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of human Cav3.2 expressed in tsA-201 cells by patch clamp electrophysiology
Measurement: IC50 = 3140 nM (pChEMBL 5.5)
Descriptors: MW 594.8, ALogP 8.21, HBA 5, HBD 1, PSA 47.94, QED 0.17
Compound (SMILES): CC1(NC(=O)COc2cccc(-c3nc4c(c(Nc5ccc(-c6cn[nH]c6)cc5)n3)CN(C3CC3)CC4)c2)CC1
InChIKey: AMQJEAXSVOXATE-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11169
Assay: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay
Measurement: IC50 = 211 nM (pChEMBL 6.679999828338623)
Descriptors: MW 535.65, ALogP 4.85, HBA 7, HBD 3, PSA 108.06, QED 0.28
Compound (SMILES): C[C@H](c1ccc(Cl)cc1Cl)n1nc(C#N)c2ncc(N3CC([C@H]4CCCN(CC(=O)O)C4)C3)nc21
InChIKey: CARIUAIHWHTGRD-CABCVRRESA-N
Target: C-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51679
Assay: Antagonist activity at CCR4 in human CCRF-CEM cells assessed as inhibition of CCL22-mediated chemotaxis preincubated for 30 mins followed by CCL22 addition and measured after 60 mins in presence of 100% human serum by CellTiter-Glo assay
Measurement: IC50 = 775 nM (pChEMBL 6.110000133514404)
Descriptors: MW 514.42, ALogP 3.85, HBA 8, HBD 1, PSA 111.17, QED 0.53
Compound (SMILES): CCNC(=O)c1ccc(Nc2nccc(N3CC4CC(C3)N4C(=O)C3CC3)n2)cc1
InChIKey: PGNNVAYXCHBCOZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human recombinant JAK1 assessed as level of phosphorylation in presence of peptide substrate 5FAM-KKSRGDYMTMQUID and ATP by mobility shift assay
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 406.49, ALogP 2.17, HBA 6, HBD 2, PSA 90.46, QED 0.76
Compound (SMILES): CN1CCC[C@H](NC(=O)[C@H]2CN(S(=O)(=O)c3ccccc3)C[C@@H]2NC(=O)c2cc(-c3ccccc3Cl)on2)C1
InChIKey: MVXOSGMOIIRSJP-XZOYJPPVSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay
Measurement: EC50 < 0.32 nM (pChEMBL 9.494999885559082)
Descriptors: MW 572.09, ALogP 2.62, HBA 7, HBD 2, PSA 124.85, QED 0.45
Compound (SMILES): C[C@H]1C(=O)C(C(N)=O)=C[C@@]2(C)c3nc(-c4ccncc4)nc(-c4ccccc4)c3CC[C@H]12
InChIKey: AHDKLJARQXFXTP-YJBDGANESA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4-positive T cells assessed as suppression of T cell differentiation to Th17 cells by reduction in measuring IL-17A secretion
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 424.5, ALogP 3.66, HBA 5, HBD 1, PSA 98.83, QED 0.65
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCNC(C)=S)NC(=O)[C@@H]1Cc2ccc(cc2)OCCCCCC(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N1)C(N)=O
InChIKey: CWPWATULNKVZGA-LJADHVKFSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of His6-tagged human SIRT2 deacetylation activity using SIRT1 acetyl-lysine as substrate in presence of beta-NAD+ after 12 mins by reversed-phase HPLC analysis
Measurement: IC50 = 1030 nM (pChEMBL 5.989999771118164)
Descriptors: MW 844.12, ALogP 1.96, HBA 10, HBD 8, PSA 238.53, QED 0.08
Compound (SMILES): COC(=O)[C@H](Cc1ccccc1)n1cc(COc2nc(Cl)nc(N3CCCC3)n2)nn1
InChIKey: SVNWXRNLNXIUEP-INIZCTEOSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX2 using arachidonic acid as substrate incubated for 10 mins followed by substrate addition and measured after 2 mins by EIA assay
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 443.9, ALogP 2.25, HBA 10, HBD 0, PSA 108.15, QED 0.48
Compound (SMILES): COc1ccc(Nc2nc(Nc3ccc(N4CCN(C)CC4)cn3)ncc2Cl)cc1
InChIKey: JJKRSPZQJWOKSJ-UHFFFAOYSA-N
Target: CDK9/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay
Measurement: IC50 = 1380 nM (pChEMBL 5.860000133514404)
Descriptors: MW 425.92, ALogP 3.77, HBA 8, HBD 2, PSA 78.44, QED 0.62
Compound (SMILES): Cc1ccccc1Nc1nc(Nc2ccc(N3CCCCC3)cn2)ncc1Cl
InChIKey: ALNCIPDHUNUCFA-UHFFFAOYSA-N
Target: CDK9/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 394.91, ALogP 5.31, HBA 6, HBD 2, PSA 65.97, QED 0.61
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CC(F)(F)C[C@@H]2C)c(C(F)F)c1F)C(F)(F)F
InChIKey: ZATVNPQFNUIWPP-FZMZJTMJSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human RORgammat LBD by M1H cell based assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 680.64, ALogP 4.88, HBA 7, HBD 3, PSA 128.7, QED 0.31
Compound (SMILES): O=C1Nc2c(O)cc(Cl)cc2C(C#CC2CC2)(C(F)(F)F)O1
InChIKey: OOVOMPCQLMFEDT-UHFFFAOYSA-N
Target: Cholesterol 24-hydroxylase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6A2
Assay: Binding affinity to recombinant human C-terminal 4His-tagged CYP46A1 delta(2 to 50) mutant expressed in Escherichia coli in presence of substrate by UV-spectrophotometric method
Measurement: Kd = 15900 nM (pChEMBL 4.800000190734863)
Descriptors: MW 331.68, ALogP 3.78, HBA 3, HBD 2, PSA 58.56, QED 0.56
Compound (SMILES): Cc1ccc2[nH]c(C(=O)N[C@@H]3CCN(S(=O)(=O)c4ccccc4)C[C@@H]3C(=O)NCCN(C)C)cc2c1
InChIKey: KDSBEDWVRJKILQ-JTHBVZDNSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Displacement of [His[125I]]-ghrelin from GHS-R1a (unknown origin) expressed in HEK293 cell membranes measured after 1 hr by microbeta counting method
Measurement: IC50 = 249 nM (pChEMBL 6.599999904632568)
Descriptors: MW 511.65, ALogP 1.96, HBA 5, HBD 3, PSA 114.61, QED 0.43
Compound (SMILES): O=C(NCCN1CCOCC1)c1ccc2c(c1)C(=O)c1ccc(Nc3ccc(F)c(/C=N/NC(=O)c4cccs4)c3)cc1CC2
InChIKey: WNIOTUHFBYIPNS-FDALDRLYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of NanoBRET kinase tracer K4 binding to full-length human C-terminal NanoLuc-tagged p38alpha MAPK expressed in HEK293T cells incubated for 2 hrs by NanoBRET NanoGlo substrate based NanoBRET assay
Measurement: IC50 = 15.5 nM (pChEMBL 7.809999942779541)
Descriptors: MW 625.73, ALogP 4.79, HBA 8, HBD 3, PSA 112.13, QED 0.18
Compound (SMILES): COc1cc2c(cc1OC)CN(CCc1ccc(NC(=O)/C=C/c3ccc(Oc4ccc(-c5ccccn5)c(Cl)c4)nc3)cc1)CC2
InChIKey: OMIMHQKYQZZELH-RIYZIHGNSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Reversal of Pgp-mediated DOX resistance in human SW620/AD300 cells assessed as concentration required to show half of DOX IC50 incubated for 48 hrs by SRB assay
Measurement: EC50 = 37.2 nM (pChEMBL 7.429999828338623)
Descriptors: MW 647.18, ALogP 7.86, HBA 7, HBD 1, PSA 85.81, QED 0.15
Compound (SMILES): CCCCCC(=O)N[C@@H](C(=O)NCc1ccc(NC(=N)N)cc1)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1.O=C(O)C(F)(F)F
InChIKey: YVVFRNAKGDTZMK-HZPIKELBSA-N
Target: Genome polyprotein (SINGLE PROTEIN), West Nile virus
UniProt: P06935
Assay: Inhibition of West Nile virus NS2B-NS3 protease expressed in Escherichia coli BL21 lambda (DE3) cells using Abz-Gly-Leu-Lys-Arg-Gly-Gly-3-(NO2)Tyr as substrate preincubated for 15 mins followed by substrate addition measured for 15 mins by fluorimetric analysis
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 569.63, ALogP 5.64, HBA 4, HBD 5, PSA 129.33, QED 0.1
Compound (SMILES): COc1ccc(CC(=O)Nc2ncc(-c3ccc(OCCCCN4CCN(Cc5ccccc5)CC4)cc3)s2)cc1OC
InChIKey: VEZTVGKHBFQQNH-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Canis lupus familiaris
UniProt: P32750
Assay: Inhibition of dog serum BChE using butrylthiocholine iodide as substrate by spectrophotometry based Ellman's method
Measurement: IC50 = 41030 nM (pChEMBL 4.389999866485596)
Descriptors: MW 600.79, ALogP 5.99, HBA 8, HBD 1, PSA 76.16, QED 0.18
Compound (SMILES): C=C(C(N)=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H](N)Cc1ccc(O)cc1)c1ccco1
InChIKey: GASMYTNMNVFTEF-ZJMAKVHZSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Displacement of [3H]-DAMGO from Wistar rat mu opioid receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 19.2 nM (pChEMBL 7.71999979019165)
Descriptors: MW 632.72, ALogP 0.23, HBA 8, HBD 9, PSA 251.68, QED 0.04
Compound (SMILES): O=C(Nc1ccc(C2(C(=O)Nc3ccc(F)cc3)COC2)cc1)c1cccc(Cl)c1
InChIKey: MFKLGMRXGXACFK-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma/LPS stimulated human whole blood assessed as unbound concentration using kynurenine/tryptophan as substrate preincubated with compound for 15 mins followed by incubation with IFNgamma/LPS for 18 hrs by LC/MS/MS analysis
Measurement: IC50 = 0.09 nM (pChEMBL 10.050000190734863)
Descriptors: MW 424.86, ALogP 4.64, HBA 3, HBD 2, PSA 67.43, QED 0.63
Compound (SMILES): N#C[C@]1(C2CC2)C(=O)N2C[C@H]1COC/C=C/COCc1cccc(n1)Nc1cc2ccn1
InChIKey: HTEKLZHVQBWTOT-RYYGKROTSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 (unknown origin)
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 431.5, ALogP 3.21, HBA 7, HBD 1, PSA 100.37, QED 0.69
Compound (SMILES): O=c1cc(C2CCCCC2)c2c[nH]nc2[nH]1
InChIKey: MCAQAKUWAWWANZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of N-terminal His-tagged human JAK2 catalytic domain incubated for 20 mins in presence of TK substrate-biotin by TR-FRET assay
Measurement: IC50 = 35000 nM (pChEMBL 4.460000038146973)
Descriptors: MW 217.27, ALogP 2.3, HBA 2, HBD 2, PSA 61.54, QED 0.77
Compound (SMILES): C=CC(=O)NCCOc1cc(Cc2ccc(OC)cc2)cc2[nH]c(-c3n[nH]c4cc(C(F)F)ccc34)cc12
InChIKey: UEXSPADOVNZDAB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) using TK as substrate incubated for 30 mins by HTRF assay
Measurement: IC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 516.55, ALogP 5.93, HBA 4, HBD 3, PSA 92.03, QED 0.16
Compound (SMILES): Cl.Clc1ncccc1OC[C@@H]1C[C@H]2C[C@H]2N1
InChIKey: JUYQSLIXKWROHJ-CTERPIQNSA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in IMR32 cell membrane by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 224.69, ALogP 1.86, HBA 3, HBD 1, PSA 34.15, QED 0.8
Compound (SMILES): Cc1c(Nc2cccc3c2CCN(C)C3)cnn(C)c1=O
InChIKey: YBLUEXMGRUAPAL-UHFFFAOYSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Binding affinity to human partial length BRD9 (R130 to V259 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Ki = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 284.36, ALogP 1.82, HBA 5, HBD 1, PSA 50.16, QED 0.91
Compound (SMILES): O=c1c2cc(-c3ccnc4[nH]ccc34)sc2ncn1Cc1cccc(F)c1
InChIKey: RCNSYAHCVQPUFD-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of recombinant human ROCK2 (11 to 552 residues) using KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK as substrate incubated for 40 mins in presence of [gamma-33P]ATP by radiometric scintillation assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 376.42, ALogP 4.19, HBA 5, HBD 1, PSA 63.57, QED 0.51
Compound (SMILES): C=CCN1CCc2cc(OC)c(O)cc2C(c2c(Cl)cccc2Cl)C1
InChIKey: NVFYXNDKOPANPI-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]SCH23390 from dopamine D5 receptor (unknown origin)
Measurement: Ki = 479.1 nM (pChEMBL 6.320000171661377)
Descriptors: MW 378.3, ALogP 4.88, HBA 3, HBD 1, PSA 32.7, QED 0.77
Compound (SMILES): CN(Cc1nc2ccsc2c(=O)[nH]1)C(=O)CCc1cccc(-c2nc3c(N)ncnc3[nH]2)c1
InChIKey: KFCAZHLXPKTXBJ-UHFFFAOYSA-N
Target: DNA (cytosine-5)-methyltransferase 3B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBC3
Assay: Inhibition of human recombinant DNMT3B expressed in baculovirus infected insect cells by DRONE assay
Measurement: IC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 460.52, ALogP 2.49, HBA 8, HBD 3, PSA 146.54, QED 0.35
Compound (SMILES): O=C(NC1CCS(=O)(=O)CC1)c1n[nH]c2ccc(-c3cccc(F)c3F)cc12
InChIKey: RLUSWBPHYRGQKM-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells assessed as reduction in tail current by measuring tail current amplitude measured after deploarization to +20 mV for 2s followed by 1s pulse to -40 mV by whole cell patch clamp assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 405.43, ALogP 2.82, HBA 4, HBD 2, PSA 91.92, QED 0.7
Compound (SMILES): Cc1ccc2[nH]c(C(=O)N[C@H]3CN(S(=O)(=O)c4cccnc4)C[C@@H]3C(=O)NCCN(C)C)cc2c1
InChIKey: CAEGAWNBFLCLSU-UGKGYDQZSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Displacement of [His[125I]]-ghrelin from GHS-R1a (unknown origin) expressed in HEK293 cell membranes measured after 1 hr by microbeta counting method
Measurement: IC50 = 14.26 nM (pChEMBL 7.849999904632568)
Descriptors: MW 498.61, ALogP 0.97, HBA 6, HBD 3, PSA 127.5, QED 0.42
Compound (SMILES): c1cn2cc(-c3cnc4nc[nH]c4n3)nc(Nc3ccc(N4CCN(C5COC5)CC4)cc3)c2n1
InChIKey: AQZVKSNGVJKVOL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK in human Ramos cells assessed as reduction in antihuman IgM F(ab)2-induced phosphorylation of BLNK at Y96 residue preincubated for 1 hr followed by antihuman IgM F(ab)2 stimulation for 5 mins by MSD high bind plate assay
Measurement: EC50 = 192 nM (pChEMBL 6.71999979019165)
Descriptors: MW 468.53, ALogP 2.33, HBA 10, HBD 2, PSA 112.39, QED 0.4
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3Cc2c[nH]c3ccccc23)cc(OC)c1OC
InChIKey: PHLKHQBIZZEZKO-MZADTFQBSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 463.58, ALogP 4.51, HBA 5, HBD 2, PSA 75.82, QED 0.54
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CCC[C@@H]2C)c(Cl)c1Cl)C(F)(F)F
InChIKey: XMVJSPSDBNHOFM-RYUDHWBXSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 631.53, ALogP 4.47, HBA 7, HBD 3, PSA 128.7, QED 0.39
Compound (SMILES): CC(=O)N[C@@H]1CCCc2c1cncc2N1C(=O)c2ccc(Cl)cc2[C@@H]1C
InChIKey: GELKDNJSUBLFHD-BBATYDOGSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Inhibition of human CYP11B1 expressed in human renal leiomyoblastoma cells harboring FDXR/FDX using 1-deoxycortisol as substrate by HTRF assay
Measurement: IC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 369.85, ALogP 3.97, HBA 3, HBD 1, PSA 62.3, QED 0.87
Compound (SMILES): C[C@]1(c2ccccc2)SC[C@@H](CN2CCC(Cc3ccccc3)CC2)S1.O=C(O)C(=O)O
InChIKey: HRWMQPOUIVAWQB-RFPXDPOKSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]-ditolylguanidine from human Sigma 2 receptor by radioligand displacement assay
Measurement: Ki = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 383.63, ALogP 5.66, HBA 3, HBD 0, PSA 3.24, QED 0.66
Compound (SMILES): O=C(NCCc1ccccc1)C(=O)c1ccc(Cl)cc1
InChIKey: QINSZKHSIICNNM-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 287.75, ALogP 2.88, HBA 2, HBD 1, PSA 46.17, QED 0.68
Compound (SMILES): CNC(=O)c1cc(C(=O)NC2CC2)cn(CC2CCOCC2)c1=O
InChIKey: DMFZQVFIJMQPMU-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to 6His-Thr-BRD4 (1 to 477 residues) BD1 domain (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 333.39, ALogP 0.53, HBA 5, HBD 2, PSA 89.43, QED 0.82
Compound (SMILES): COc1cc(C(=O)N2CC(F)C2)ccc1Nc1nc2ccc(-c3ccc(NC(=O)Cc4ccc(F)cc4)cc3)cn2n1
InChIKey: YQYUXBURDZCWLY-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Mps-1 Kinase Assay: For the assay 50 nl of a 100-fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (Greiner Bio-One, Frickenhausen, Germany), 2 μl of a solution of Mps-1 in assay buffer [0.1 mM sodium-ortho-vanadate, 10 mM MgCl2, 2 mM DTT, 25 mM Hepes pH 7.7, 0.05% BSA, 0.001% Pluronic F-127] were added and the mixture was incubated for 15 min at 22° C. to allow pre-binding of the test compounds to Mps-1 before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 μl of a solution of 16.7 adenosine-tri-phosphate (ATP, 16.7 μM=>final conc. in the 5 μl assay volume is 10 μM) and peptide substrate (1.67 μM=>final conc. in the 5 μl assay volume is 1 μM) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22° C. The concentration of Mps-1 in the assay was adjusted to the activity of the enzyme lot and was chosen appropriate to have the assay in the linear range, typical enzyme concentrations were in the range of about 1 nM (final conc. in the 5 μl assay volume). The reaction was stopped by the addition of 3 μl of a solution of HTRF detection reagents (100 mM Hepes pH 7.4, 0.1% BSA, 40 mM EDTA, 140 nM Streptavidin-XLent [#61GSTXLB, Fa. Cis Biointernational, Marcoule, France], 1.5 nM anti-phospho(Ser/Thr)-Europium-antibody [#AD0180, PerkinElmer LAS, Rodgau-Jügesheim, Germany].The resulting mixture was incubated 1 h at 22° C. to allow the binding of the phosphorylated peptide to the anti-phospho(Ser/Thr)-Europium-antibody. Subsequently the amount of phosphorylated substrate was evaluated by measurement of the resonance energy transfer from the Europium-labelled anti-phospho(Ser/Thr) antibody to the Streptavidin-XLent. Therefore, the fluorescence emissions at 620 nm and 665 nm after excitation at 350 nm was measured in a Viewlux TR-FRET reader (PerkinElmer LAS, Rodgau-Jügesheim, Germany). The “blank-corrected normalized ratio” (a Viewlux specific readout, similar to the traditional ratio of the emissions at 665 nm and at 622 nm, in which blank and Eu-donor crosstalk are subtracted from the 665 nm signal before the ratio is calculated) was taken as the measure for the amount of phosphorylated substrate. The data were normalised (enzyme reaction without inhibitor=0% inhibition, all other assay components but no enzyme=100% inhibition).
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 568.58, ALogP 5.26, HBA 7, HBD 2, PSA 100.86, QED 0.26
Compound (SMILES): [O-][S+](CCN1CCN(CC(O)Cc2ccc(C(F)(F)F)cc2)CC1)C(c1ccc(F)cc1)c1ccc(F)cc1
InChIKey: QYNMPWDKGXROKT-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]citalopram from SERT in Sprague-Dawley rat midbrain membranes incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 11600 nM (pChEMBL 4.940000057220459)
Descriptors: MW 566.64, ALogP 5.04, HBA 4, HBD 1, PSA 49.77, QED 0.28
Compound (SMILES): CCCCn1c(=O)sn(-c2cccc3ccccc23)c1=O
InChIKey: KHBILWSKMYQGPN-UHFFFAOYSA-N
Target: Sortase A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: Q9S446
Assay: Inhibition of Staphylococcus aureus SrtA delta N24 mutant expressed in Escherichia coli BL21 (DE3) using Abz-LPATG-Dnp substrate incubated for 20 mins by FRET-based assay
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 300.38, ALogP 3.01, HBA 5, HBD 0, PSA 44, QED 0.74
Compound (SMILES): COc1c(OCCOCCOCCOCCOCCOCCOCCOCCOc2ccc(C3CCN(c4ccn5c(CC6CC6)nnc5c4Cl)CC3)cc2)cccc1C(=O)C1CCN(CCc2ccc(F)cc2)CC1
InChIKey: KEOUMVRTMMZTEV-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Agonist activity at human mGlu2 receptor expressed in HEK293 cells co-expressing Gqo5 assessed as increase in intracellular Ca2+ mobilization incubated for 1 hr by Fluo-4 dye based fluorescence assay
Measurement: EC50 = 1548.82 nM (pChEMBL 5.809999942779541)
Descriptors: MW 1074.73
Compound (SMILES): COc1ccc(-c2c(C)nc3c(N4CC[C@@H](NC(C)=O)C4)ccnn23)cc1OC
InChIKey: OGNCVDCZXXFLIH-MRXNPFEDSA-N
Target: Sphingomyelin phosphodiesterase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NY59
Assay: Fluorescence Based Assay: The fluorescence based assay to monitor the activity of human nSMase2 in the presence or absence of potential inhibitors has been described recently. Figuera-Losada, et al. Lysate of cells expressing recombinant nSMase2 is used to catalyze the hydrolysis of sphingomyelin (SM) to ceramide and phosphorylcholine. Phosphorylcholine undergoes dephosphorylation in a reaction catalyzed by alkaline phosphatase (4 U/mL) to produce choline which in turn is oxidized by choline oxidase (0.1 U/mL) to betaine and hydrogen peroxide (H2O2). Hydrogen peroxide is made to react with Amplex red (50 μM) in the presence of horseradish peroxidase (HRP, 1 U/mL) to generate the fluorescent molecule resorufin. Generation of fluorescence is monitored by measuring relative florescence units (RFU) with excitation at 530 nm and emission at 590 nm. Extent of fluorescence is directly proportional to the extent of SM hydrolysis. Substrate stock solution is prepared in 2% Triton X-100 and sonicated for 1 min. Reactions are carried out for 1 h at 37° C. in 100 mM Tris-HCl pH 7.4, 10 mM MgCl2, 0.2% Triton X-100. This assay has been optimized in 384-well format (50 μL total volume per well) under conditions where nSMase2-catalyzed hydrolysis of SM is linear with respect to nSMase2 concentration, time of incubation and SM concentration (FIGS. 3A-3C). The assay has high reliability (Z′=0.8-0.9). It is used for compound screening, IC50 determinations and mode of inhibition studies
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 395.46, ALogP 2.44, HBA 7, HBD 1, PSA 80.99, QED 0.71
Compound (SMILES): COc1ccc(CCC(C)(C)NC[C@H](O)c2cc(O)cc3c2OCC(=O)N3)cc1.Cl
InChIKey: OIDAYKYKCHRSFN-FYZYNONXSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Agonist activity at human beta1 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay
Measurement: EC50 = 8.128 nM (pChEMBL 8.09000015258789)
Descriptors: MW 400.48, ALogP 2.77, HBA 6, HBD 4, PSA 100.05, QED 0.54
Compound (SMILES): CC1(C)C(/C=C/C=C/C=C2\N(CCCCCC(=O)NCCCCNc3c(NCCCOc4cccc(CN5CCCCC5)c4)c(=O)c3=O)c3ccccc3C2(C)C)=[N+](CCCCS(=O)(=O)[O-])c2ccccc21.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: APTAKTZLMIPLMI-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Binding affinity to human H2R expressed in human HEK293T cells incubated for 90 mins by flowcytometry
Measurement: Kd = 562.34 nM (pChEMBL 6.25)
Descriptors: MW 1001.35
Compound (SMILES): O=C(O)c1cc(-c2ccc(C34CCN(CC3)CC4)cc2)c2ccc(-c3ccc(C(F)(F)F)cc3)cc2c1
InChIKey: SSHPNRDLABGEOD-UHFFFAOYSA-N
Target: P2Y purinoceptor 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15391
Assay: Inhibition of MRS4174 binding to human P2Y14R expressed in CHO cells pre-incubated for 30 mins before MRS4174 addition and further incubated for 30 mins at pH 7.4 by flow cytomtery based competitive fluorescence assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 501.55, ALogP 7.63, HBA 2, HBD 1, PSA 40.54, QED 0.31
Compound (SMILES): CNC(=O)c1cc(C(=O)NC2CCC2)cn(Cc2ccncc2)c1=O
InChIKey: YHYKIXZUZVEISM-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to 6His-Thr-BRD4 (1 to 477 residues) BD1 domain (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 340.38, ALogP 0.93, HBA 5, HBD 2, PSA 93.09, QED 0.85
Compound (SMILES): C=CC(=O)NCCOc1cc(C(OCCS(C)(=O)=O)c2ccccc2)cc2[nH]c(-c3n[nH]c4cc(C(F)F)ccc34)cc12
InChIKey: XRXVQPNHFLSJCG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) using TK as substrate incubated for 30 mins by HTRF assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 608.67, ALogP 5.48, HBA 6, HBD 3, PSA 126.17, QED 0.12
Compound (SMILES): CCS(=O)(=O)N[C@@H]1CCCc2c1cncc2N1Cc2cc(Cl)ccc2C1=O
InChIKey: BDBOXLKCKSSACN-QGZVFWFLSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Inhibition of human CYP11B1 expressed in human renal leiomyoblastoma cells harboring FDXR/FDX using 1-deoxycortisol as substrate by HTRF assay
Measurement: IC50 = 1788 nM (pChEMBL 5.75)
Descriptors: MW 405.91, ALogP 3.21, HBA 4, HBD 1, PSA 79.37, QED 0.85
Compound (SMILES): Nc1ccccc1-c1cc(NC2CCCNC2)c2ccncc2c1
InChIKey: FKJNUFATJIQZEN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase D2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZL6
Assay: Inhibition of PKD2 (unknown origin)
Measurement: IC50 = 187 nM (pChEMBL 6.730000019073486)
Descriptors: MW 318.42, ALogP 3.65, HBA 4, HBD 3, PSA 62.97, QED 0.65
Compound (SMILES): CN1C(=O)N(c2ccc3[nH]ncc3c2)C2(CCN(C(=O)CNC(=O)c3cc(C(F)(F)F)ccc3F)CC2)C1=O
InChIKey: RTUNYIMDFLSMRE-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Autotaxin LPC Cascade Assay: The efficacy of the Examples described herein, as inhibitors of ATX are demonstrated and confirmed by pharmacological in vitro assays. The following assays and their respective methods are carried out with the compounds according to the present invention. Activity possessed by the compounds may be demonstrated in vivo. Those skilled in the art will appreciate that a variety of assay formats may be used to determine the activity of the compounds of this invention.Autotaxin LPC Cascade Assay:Assay Buffer:100 mM Tris-HCl, pH=9500 mM NaCl5 mM MgCl25 mM CaCl20.05% Triton X 100Reagents:Enzyme Source Stock conc Working conc. Final conc. Autotaxin X-Chem 4.6 μM 20 nM 5 nM LPC Sigma L5254 8 mM in assay buffer 400 μM 100 μM Choline Oxidase Sigma C5896 50 U/mL in water 0.8 U/mL 0.1 U/mL HRP Sigma P8375 1000 U/mL in water 8 U/mL 1 U/mL Ampliflu Red Sigma 90101 100 mM in DMSO 400 μM 50 μM.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 546.48, ALogP 2.91, HBA 5, HBD 2, PSA 118.71, QED 0.39
Compound (SMILES): C[N+]1(C)CCC(COC(=O)Nc2ccc(F)cc2-c2ccc(F)c(Cl)c2)CC1.O=C[O-]
InChIKey: WFJDEWRFSIRFAG-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M2 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method
Measurement: Ki = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 409.88, ALogP 5.32, HBA 2, HBD 1, PSA 38.33, QED 0.69
Compound (SMILES): CSCC[C@@H]1NC(=O)[C@@H](NC(=O)[C@H](CCCCNC(C)=S)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2c[nH]cn2)NC(C)=O)Cc2ccc(cc2)OCCCCCCCNC1=O
InChIKey: OWCFZCRQZWNKAO-LQWITFIISA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of His6-tagged human SIRT2 deacetylation activity using SIRT1 acetyl-lysine as substrate in presence of beta-NAD+ after 12 mins by reversed-phase HPLC analysis
Measurement: IC50 = 25500 nM (pChEMBL 4.590000152587891)
Descriptors: MW 901.21, ALogP 2.09, HBA 11, HBD 9, PSA 250.56, QED 0.06
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4nc(C)n([C@@H](COC)c5ccc(F)cc5)c(=O)c4c3)cc12
InChIKey: IWHVQSGPUREPKO-HKBQPEDESA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase in HCV genotype 1b by Taqman probe based RT-PCR analysis
Measurement: EC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 686.74, ALogP 6.05, HBA 8, HBD 1, PSA 123.74, QED 0.2
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2CCOC[C@H]2Cn2ccc(-c3ccc(F)cn3)n2)c1
InChIKey: OKROKECXNXWALA-GOSISDBHSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Antagonist activity at human recombinant OX2R expressed in CHOK1 cells assessed as inhibition of orexin A-induced intracellular Ca2+ release preincubated for 30 mins followed by orexin-A stimulation by Fluo-4AM dye based fluorescence analysis
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 447.47, ALogP 2.51, HBA 8, HBD 0, PSA 90.96, QED 0.47
Compound (SMILES): Cc1cccc(N2CCN(CCCC(=O)NCn3nc(CC(N)=O)c4ccccc4c3=O)CC2)c1C
InChIKey: JIXPXSOVIFRGMG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]mesulergine from 5-HT2C receptor (unknown origin) by cell based radioligand competitive binding analysis
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 490.61, ALogP 1.72, HBA 7, HBD 2, PSA 113.56, QED 0.47
Compound (SMILES): COc1ccc(C(=O)CSc2nccc(Nc3ccc(S(=O)(=O)Nc4cncs4)cc3)n2)cc1
InChIKey: HQXNZYLYIOQNNP-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 dye based stopped-flow CO2 hydration assay
Measurement: Ki = 880 nM (pChEMBL 6.059999942779541)
Descriptors: MW 513.63, ALogP 4.46, HBA 10, HBD 2, PSA 123.17, QED 0.18
Compound (SMILES): C[N+](C)(C)C[C@@H]1CO[C@@H](c2ccc(-c3ccccc3)cc2)CO1.[I-]
InChIKey: HLUWWAVNYXZULY-GZJHNZOKSA-M
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M2 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 3235.94 nM (pChEMBL 5.489999771118164)
Descriptors: MW 312.43, ALogP 3.52, HBA 2, HBD 0, PSA 18.46, QED 0.8
Compound (SMILES): N#C[C@]1(C2CC2)C(=O)N2C[C@H]1COCC(=O)NCCc1cccc(n1)Nc1cc2ccn1
InChIKey: VHPOHFDPEQHMMX-QMHKHESXSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 (unknown origin)
Measurement: IC50 = 910 nM (pChEMBL 6.039999961853027)
Descriptors: MW 432.48, ALogP 1.79, HBA 7, HBD 2, PSA 120.24, QED 0.7
Compound (SMILES): N#Cc1cccc(/C=C/C(=O)c2cc(O)c(O)c([N+](=O)[O-])c2)c1
InChIKey: RDFONYBBJNORFN-SNAWJCMRSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAOB using kynuramine as substrate by fluorescence based assay
Measurement: IC50 = 60600 nM (pChEMBL 4.21999979019165)
Descriptors: MW 310.27, ALogP 2.77, HBA 6, HBD 2, PSA 124.46, QED 0.29
Compound (SMILES): N#CN1CC(COCc2ccc(-c3ccccc3)cc2)C1
InChIKey: NBQWOCLGPPLYNW-UHFFFAOYSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition Assay: In order to have an assay method more conducive to high-throughput screening than those published for measuring the NAE hydrolyzing activity of NAAA, we developed the fluorogenic PEA analog N-(4-methyl coumarin)palmitamide (PAMCA), which is hydrolyzed to fluorescent 7-amino-4-methyl coumarin (AMC) and palmitic acid. For three point concentration inhibition assays with hNAAA the following procedure is used. Purified activated NAAA (final concentration of 0.25 μg/mL) is incubated in assay buffer (100 mM citrate-phosphate buffer, pH 4.5, 3 mM DTT, 0.1% Triton X-100, 0.05% BSA, and 150 mM NaCl) made up to a total volume of 180 μL, followed by addition of the compound dissolved in 10 μL DMSO (along with DMSO neat for the control sample) with the final concentrations for each compound of 100, 10, and 1 μM, in triplicate on a 96 well plate. These samples are allowed to incubate for 15 min at room temperature and then 10 μL of a PAMCA stock solution in DMSO (final PAMCA concentration [5 μM]) was added. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes, with fluorescence readings taken every 10 minutes at a wavelength of 460 nm (using an excitation wavelength of 360 nm) on a Synergy HT Plate Reader using Gen5 software from Bio-Tek. The enzyme activity is calculated by converting the relative fluorescence units to AMC formed, using a standard curve of AMC. For compounds that inhibit hNAAA in range IC50 <1 μM full inhibition curves using eight different concentrations of inhibitor (8 point assay) are generated. The assay procedure used is the same as the three point assay. For ostensibly covalent compounds (as observed by a significant decrease in the slope of a plot of fluorescence vs. time in three point screen) samples are allowed to incubate for 2 hours at 37° C., instead of 15 minutes, before addition of 10 μL of a PAMCA stock solution in DMSO for a final PAMCA concentration of 5 μM. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes Inhibition constants are calculated using pro Fit software (Quantum Soft, Uetikon am See, Switzerland) and a Levenberg-Marquardt algorithm.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 278.36, ALogP 3.28, HBA 3, HBD 0, PSA 36.26, QED 0.79
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc2c(n1)N(Cc1ccccc1)c1ccccc1C(=O)N2C
InChIKey: JVSJTGAAAMSIAW-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of recombinant human GST-tagged LRRK2 catalytic domain (970 to 2527 residues) expressed in baculovirus expression system using LRRKtide as substrate measured after 1 hr by Alexa fluor-647 ADP tracer-based ADAPTA assay
Measurement: IC50 = 141 nM (pChEMBL 6.849999904632568)
Descriptors: MW 535.65, ALogP 4.91, HBA 8, HBD 1, PSA 77.07, QED 0.37
Compound (SMILES): Cc1ccccc1CNc1cnn(C)c(=O)c1C
InChIKey: FFMGVTIFJAWKJQ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to BRD4 (1) (unknown origin) N-terminal bromodomain by TR-FRET assay
Measurement: IC50 = 25118.86 nM (pChEMBL 4.599999904632568)
Descriptors: MW 243.31, ALogP 2.01, HBA 4, HBD 1, PSA 46.92, QED 0.9
Compound (SMILES): C[C@H]1COc2c(N3CCN(C)CC3)c(F)cc3c(=O)c(C(=O)OCc4cn(CCCCCC(=O)NO)nn4)cn1c23
InChIKey: FSMZRUMFZQTTIO-KRWDZBQOSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human HDAC2 incubated for 30 mins by SpectraMax M2 microplate reader analysis
Measurement: IC50 = 134 nM (pChEMBL 6.869999885559082)
Descriptors: MW 571.61, ALogP 1.86, HBA 12, HBD 2, PSA 144.05, QED 0.16
Compound (SMILES): Clc1nc(OCc2cn(Cc3ccccc3)nn2)nc(N2CCCC2)n1
InChIKey: JAMGXUJTALDXFB-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX2 using arachidonic acid as substrate incubated for 10 mins followed by substrate addition and measured after 2 mins by EIA assay
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 371.83, ALogP 2.34, HBA 8, HBD 0, PSA 81.85, QED 0.66
Compound (SMILES): Nc1nc(NCC2CCN(CC(=O)NCCc3ccc(S(N)(=O)=O)cc3)CC2)nc2sc(-c3ccco3)nc12
InChIKey: HRFFVTWCZHFHFN-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]ZM241383 from human A2AR expressed in CHO cells by competitive binding assay
Measurement: Ki = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 570.7, ALogP 2.06, HBA 11, HBD 4, PSA 182.36, QED 0.22
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3cnc(CC(C)(C)C(=O)O)s3)nc2CC2CCC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: FQNXGRKEBPOPHJ-LBPRGKRZSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human whole blood assessed as reduction in IL-17a production
Measurement: IC50 = 2025 nM (pChEMBL 5.690000057220459)
Descriptors: MW 656.6, ALogP 7.47, HBA 7, HBD 2, PSA 109.25, QED 0.23
Compound (SMILES): C=CC(=O)Nc1cccc(Nc2nc(Nc3ccc4c(c3)B(O)OC4(C)C)ncc2C(F)(F)F)c1
InChIKey: IPDZMASQNCOZLU-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human N-terminal GST-tagged TYK2 (871 to 1187 residues) expressed in baculovirus expression system using Ulight-Poly GT as substrate incubated for 2 hrs by Lanthascreen TR-FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 483.26
Compound (SMILES): Cc1ccc2nc(-c3cccc([N+](=O)[O-])c3)[nH]c2c1
InChIKey: PACRMTWAYUPJIE-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 catalytic domain (Phe99 to Gln269 residues) expressed in Escherichia coli cells using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2/TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6'-TAMRA)-Ala-Lys-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 27000 nM (pChEMBL 4.570000171661377)
Descriptors: MW 253.26, ALogP 3.45, HBA 3, HBD 1, PSA 71.82, QED 0.56
Compound (SMILES): COc1ccccc1N1CCN(CCCCCCN2C(=O)[C@@H]3[C@H]4CC[C@H](C4)[C@@H]3C2=O)CC1
InChIKey: XACKNAOULJGCTD-XZOTUCIWSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from human 5HT1A receptor expressed in HEK293 cell membranes measured after 1 hr by microbeta counting method
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 439.6, ALogP 3.41, HBA 5, HBD 0, PSA 53.09, QED 0.44
Compound (SMILES): O=C(Nc1nccs1)/C(=N/N1CCCC1)c1ccc(S(=O)(=O)C2CC2)cc1
InChIKey: IDPHEZLKJAWRMK-LTGZKZEYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 17500 nM (pChEMBL 4.760000228881836)
Descriptors: MW 404.52, ALogP 2.52, HBA 7, HBD 1, PSA 91.73, QED 0.75
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nnc(C3CCCC3)o2)cc1
InChIKey: KFTFDFNRQGFJGJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 using 4-NPA as substrate measured for 3 mins by spectrophotometry
Measurement: Ki = 9.8 nM (pChEMBL 8.010000228881836)
Descriptors: MW 293.35, ALogP 2.04, HBA 5, HBD 1, PSA 99.08, QED 0.93
Compound (SMILES): Brc1cc2c(s1)CCC(NCCCCc1ccccc1)CC2
InChIKey: SYIKAIKFTMRTJJ-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from sigma1 receptor in guinea pig brain membranes incubated for 120 mins by scintillation counting method
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 378.38, ALogP 5.37, HBA 2, HBD 1, PSA 12.03, QED 0.53
Compound (SMILES): COCCOc1ccc(C2CCN(c3ccn4c(CC5CC5)nnc4c3Cl)CC2)cc1
InChIKey: KNQSTKIOHAWYMV-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Agonist activity at human mGlu2 receptor expressed in HEK293 cells co-expressing Gqo5 assessed as increase in intracellular Ca2+ mobilization incubated for 1 hr by Fluo-4 dye based fluorescence assay
Measurement: EC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 440.98, ALogP 4.74, HBA 6, HBD 0, PSA 51.89, QED 0.47
Compound (SMILES): CC(C)(C)c1cc(C(=O)NOCCCCCC(=O)NO)cc(C(C)(C)C)c1
InChIKey: PCYKSKSJYJIDFL-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant human HDAC4
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 378.51, ALogP 4.01, HBA 4, HBD 3, PSA 87.66, QED 0.36
Compound (SMILES): O=C1[C@@H]2[C@H]3CC[C@H](C3)[C@@H]2C(=O)N1CCCCCCN1CCN(c2ccccc2Cl)CC1
InChIKey: LRGSUAGMMWSFMF-ZIIYYELXSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from human 5HT1A receptor expressed in HEK293 cell membranes measured after 1 hr by microbeta counting method
Measurement: Ki = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 444.02, ALogP 4.05, HBA 4, HBD 0, PSA 43.86, QED 0.45
Compound (SMILES): CCOc1cc(Cl)c(-c2ncc(-c3nc4ccc(S(=O)(=O)C5CCN(C)CC5)cc4s3)c(=O)[nH]2)cc1N1CCOCC1
InChIKey: KGZNYDFUINOSHN-UHFFFAOYSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Displacement of [125I]-ghrelin from human GHS-R1a stably expressed in HEK cell membrane measured after 60 mins by gamma counter method
Measurement: IC50 > 18000 nM (pChEMBL 4.744999885559082)
Descriptors: MW 630.19, ALogP 4.47, HBA 10, HBD 1, PSA 117.72, QED 0.32
Compound (SMILES): NC(=O)C12CC3CC(C1)C(NC(=O)CN1CCCN(c4c(Cl)cc(C(F)(F)F)cc4Cl)S1(=O)=O)C(C3)C2
InChIKey: ALGBUNXBBMVLMQ-UHFFFAOYSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P50172
Assay: Inhibition of mouse 11beta-HSD1 expressed in CHOK1 cells using XL665-labeled cortisol as substrate measured after 24 hrs by HTRF assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 583.46, ALogP 3.57, HBA 4, HBD 2, PSA 112.81, QED 0.55
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2ccc(-c3cn(-c4ccc(OCCN5CCOCC5)cc4Cl)nn3)cc2)no1
InChIKey: MHITTXFPZXWLMH-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Binding affinity to recombinant human CSF1R (564 to 939 residues) expressed in bacterial expression system by Kinomescan method
Measurement: Kd = 100 nM (pChEMBL 7)
Descriptors: MW 566.06, ALogP 5.23, HBA 9, HBD 2, PSA 119.57, QED 0.3
Compound (SMILES): Cc1nn([C@H](C)c2ccc(Cl)cc2Cl)c2nc(N3CC([C@H]4CCCN(CCNC(=O)C(C)C)C4)C3)cnc12
InChIKey: CAMWZEJZATYASI-UXHICEINSA-N
Target: C-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51679
Assay: Antagonist activity at CCR4 in human CCRF-CEM cells assessed as inhibition of CCL22-mediated chemotaxis preincubated for 30 mins followed by CCL22 addition and measured after 60 mins in presence of 100% human serum by CellTiter-Glo assay
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 558.56, ALogP 4.97, HBA 7, HBD 1, PSA 79.18, QED 0.42
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(SCc4ncc(C(C)(C)C)o4)s3)C2)nc1
InChIKey: UVGATDDZBKJSAL-QGZVFWFLSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of recombinant human full-length His-tagged CDK7/Cyclin H/MNAT1 expressed in baculovirus infection system using Cdk7/9tide as substrate measured after 1 hr by Alexa Fluor 647 ADP Tracer-based Adapta assay
Measurement: IC50 = 3890 nM (pChEMBL 5.409999847412109)
Descriptors: MW 526.69, ALogP 4.96, HBA 9, HBD 2, PSA 113.25, QED 0.31
Compound (SMILES): CCN(C(=O)c1nc(C(=O)NCC(C)(C)O)sc1-c1ccc(S(=O)(=O)N[C@@H](C)C(F)(F)F)c(Cl)c1Cl)C1CCC1
InChIKey: GQVQGLYCTUATAE-LBPRGKRZSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 0.53 nM (pChEMBL 9.279999732971191)
Descriptors: MW 645.55, ALogP 4.86, HBA 7, HBD 3, PSA 128.7, QED 0.34
Compound (SMILES): CCOC(=O)C1=C(N)Oc2cc(O)ccc2C1c1ccc(OCCN2CCOCC2)cc1
InChIKey: WYRRSMDDEYVOMD-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Displacement of fluorescent estrogen ligand from recombinant human full length untagged ERbeta expressed in baculovirus infected insect cells incubated in dark for 2 hrs by Beacon single-tube fluorescent polarization assay
Measurement: IC50 = 2440 nM (pChEMBL 5.610000133514404)
Descriptors: MW 440.5, ALogP 2.36, HBA 8, HBD 2, PSA 103.48, QED 0.63
Compound (SMILES): O=C(CCCc1ccccc1)C(=O)NCCc1ccccc1
InChIKey: HAOXGZIOJIHAMB-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 295.38, ALogP 2.94, HBA 2, HBD 1, PSA 46.17, QED 0.76
Compound (SMILES): CN(C)Cc1ccc(-n2cc(-c3ccc4cc[nH]c4c3)c3c(Cl)ccnc32)cc1
InChIKey: MEHXWAPPUMNIFQ-UHFFFAOYSA-N
Target: Myeloperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P05164
Assay: Inhibition of human plasma myeloperoxidase
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 400.91, ALogP 5.89, HBA 3, HBD 1, PSA 36.85, QED 0.41