lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=c1cc(/C=C/c2nc3ccccc3o2)occ1O
InChIKey: XQHYAPZLHHEVHY-AATRIKPKSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of self-induced amyloid beta (1 to 42) (unknown origin) aggregation by ThT fluorescence assay
Measurement: IC50 = 7050 nM (pChEMBL 5.150000095367432)
Descriptors: MW 255.23, ALogP 2.66, HBA 5, HBD 1, PSA 76.47, QED 0.76
Compound (SMILES): COc1cc(C=C2C(=O)OC(c3ccccc3)OC2=O)cc(C(=O)OCc2ccccc2)c1O
InChIKey: HYLKQZQTQDNEDN-MOSHPQCFSA-N
Target: NAD-dependent protein deacetylase sirtuin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96EB6
Assay: Inhibition of N-terminal hexa-His-tagged human SIRT1 (156 to 664 residues) expressed in Escherichia coli BL21 (DE3) assessed as deacetylation of Abz-labeled acetyl peptide using Abz-GVLKacAYNO2GY-NH2 peptide as substrate incubated for 30 mins in presence of NAD+ by fluorescence microplate reader assay
Measurement: IC50 = 2660 nM (pChEMBL 5.579999923706055)
Descriptors: MW 460.44, ALogP 3.94, HBA 8, HBD 1, PSA 108.36, QED 0.33
Compound (SMILES): CN1C[C@@H](c2ccccc2Br)[C@@]2(CSc3ccccc3C2=O)C12C(=O)c1ccccc1C2=O
InChIKey: INXVSGLSCYSPBK-RXFWQSSRSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE (unknown origin) using acetylthiocholine chloride as substrate preincubated with enzyme for 15 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 27100 nM (pChEMBL 4.570000171661377)
Descriptors: MW 518.43, ALogP 5.27, HBA 5, HBD 0, PSA 54.45, QED 0.41
Compound (SMILES): Cc1ccc2nc(NC(=O)c3ncn(CC(=O)NCc4ccc5c(c4)OCO5)n3)[nH]c2c1
InChIKey: FPKFIIPMUISEER-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase, H3 lysine-79 specific (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TEK3
Assay: Inhibition of recombinant human N-terminal GST-tagged DOT1L (1 to 420 residues) expressed in Escherichia coli BL21 (DE3) using histone as substrate incubated for 1 hr by MTase-glo based luminescence assay
Measurement: IC50 = 55600 nM (pChEMBL 4.25)
Descriptors: MW 433.43, ALogP 1.76, HBA 8, HBD 3, PSA 136.05, QED 0.42
Compound (SMILES): COc1ccc(C[C@@H]2NC(=O)[C@H](Cc3cnc[nH]3)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc3c[nH]c4ccc(F)cc34)NC(=O)[C@H](Cc3c[nH]c4ccc(F)cc34)NC(=O)[C@@H](C)NC(=O)[C@H](CCCCN(C)C)NC(=O)CCSCc3cccc(c3)CSCCNC(=O)[C@]3(C)CCCN3C2=O)cc1
InChIKey: UILDURBDBOXHFF-WGGATNBXSA-N
Target: Proprotein convertase subtilisin/kexin type 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NBP7
Assay: Inhibition of AlexaFluor647-tagged cyclic peptide binding to avi-tagged-biotinylated human PCSK9 measured after 2 hrs by Lance Streptavidin Europium based FRET assay
Measurement: Ki = 4.2 nM (pChEMBL 8.380000114440918)
Descriptors: MW 1443.71
Compound (SMILES): O=c1c2cc(F)ccc2n2c(=S)[nH]nc2n1CCP(=O)(O)O
InChIKey: KTUNLJXBRLDWKB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of biotin-Ahx-CETFDPPLHSpTAI-NH2 binding to recombinant human full-length HA-EGFP-tagged Plk1 PBD expressed in HEK293A cells preincubated for 30 mins followed by biotin-Ahx-CETFDPPLHSpTAI-NH2 addition and measured after 1 hr by 3,3',5,5'-tetramethylbenzidine substrate based ELISA
Measurement: IC50 = 21700 nM (pChEMBL 4.659999847412109)
Descriptors: MW 344.26, ALogP 1.02, HBA 6, HBD 3, PSA 112.62, QED 0.48
Compound (SMILES): CC(C)C(c1ccc(-c2ccc3cccc(F)c3c2)[nH]c1=O)C1C(=O)NC(=O)N1C
InChIKey: OXVFJOAEQVCXLP-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Displacement of [3H]-PGE2 from human EP3 expressed in Chem-1 cell membranes incubated for 2 hrs by TopCount scintillation plate reader analysis
Measurement: Ki = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 407.45, ALogP 3.62, HBA 3, HBD 2, PSA 82.27, QED 0.65
Compound (SMILES): O=C(NCCO)c1cccc2c1CCN2c1nccc(C(O)c2cc(F)cc(C(F)(F)F)c2)n1
InChIKey: HALHLDJMKQYAIR-UHFFFAOYSA-N
Target: G-protein coupled receptor 52 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2T5
Assay: Agonist activity at human GPR52 expressed in HEK293 cells assessed as increase in cAMP levels incubated for 15 mins by Glosensor cAMP assay
Measurement: EC50 = 399 nM (pChEMBL 6.400000095367432)
Descriptors: MW 476.43, ALogP 3.13, HBA 6, HBD 3, PSA 98.58, QED 0.47
Compound (SMILES): CCC[C@@H](NC(=N)NC(=O)Cc1ccc(OC)c(OC)c1)C(=O)Nc1cc(S(N)(=O)=O)ccc1C.O=C(O)C(F)(F)F
InChIKey: HBEUXKTXZMENHE-UNTBIKODSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of human liver Cathepsin D preincubated for 10 mins followed by substrate addition and further incubated for 2 hrs in dark by fluorimetric analysis
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 505.6, ALogP 1.65, HBA 7, HBD 5, PSA 172.7, QED 0.24
Compound (SMILES): C[C@@H](c1nc2ccc(Cl)cc2[nH]1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: WGMKPGXMULYDDV-OAGGEKHMSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma/LPS-stimulated human whole blood preincubated for 4 hrs followed by IFNgamma/LPS stimulation and incubated for 18 hrs by Rapid-fire mass spectrometry analysis
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 407.92, ALogP 6.98, HBA 2, HBD 1, PSA 41.57, QED 0.4
Compound (SMILES): CCCCCCCCCCn1cc(-c2noc([C@@H]3CCCN3C(=N)N)n2)c2ccccc21.Cl
InChIKey: AKMMADIWBSJCSQ-FTBISJDPSA-N
Target: Sphingosine kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYA1
Assay: Inhibition of recombinant human Sphk1 expressed in baculovirus infected Sf9 insect cells using d-erythro-sphingosine as substrate measured after 20 mins in presence of [gamma-32P]ATP by liquid scintillation counting analysis
Measurement: Ki > 10 nM (pChEMBL 8)
Descriptors: MW 436.6, ALogP 5.86, HBA 5, HBD 2, PSA 96.96, QED 0.22
Compound (SMILES): O=C(Nc1cncc(-c2ccc3[nH]nc(-c4cc5c(-c6cccnc6)cncc5[nH]4)c3c2)c1)C1CCCC1
InChIKey: WYWUKSHABYDIOO-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 499.58, ALogP 6.36, HBA 5, HBD 3, PSA 112.24, QED 0.26
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1C(=O)Nc1ccc(C(=O)O)cc1F
InChIKey: LCFQGSRRJKESSW-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 10 mins in presence of NADPH generating system by LC-MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 479.31, ALogP 6.06, HBA 3, HBD 2, PSA 79.29, QED 0.37
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2c(F)cccc2OC)[nH]1
InChIKey: PUQQLJRQMBGCFT-GGAORHGYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 512.67, ALogP 5.43, HBA 5, HBD 2, PSA 87.32, QED 0.35
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2ccc(C(=O)Nc3cc(C(F)(F)F)ccn3)cc2OC)[nH]1
InChIKey: AECGLXAAHBEOEW-IZLXSDGUSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 119 nM (pChEMBL 6.920000076293945)
Descriptors: MW 682.79, ALogP 6.96, HBA 7, HBD 3, PSA 129.31, QED 0.15
Compound (SMILES): CCS(=O)(=O)c1ccc(CNc2nc3cnc(-c4c(OC(C)C)ncnc4C4CC4)nc3n(C(C)C)c2=O)nc1
InChIKey: DJDBLWDBBWTLMC-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Reporter Gene Assay: A nuclear receptor transactivation assay is performed to quantitate the ability of test compounds to inhibit RORγ transactivation of a luciferase reporter. A similar assay is described in: Khan et al., Bioorganic & Medicinal Chemistry Letters 23 (2013), 532-536. The system uses transiently transfected HEK 293 cells cotransfected with two plasmids (pGL4.3, luc2P/GAL4UAS/Hygro, and pBIND, Gal4DBD hRORC LBD1-3). The positive control is co-transiently transfected with both plasmids, and the negative control contains the pGL4.3 promoter sequence. Assays are assembled in 384 well plates where transiently transfected cells and test compound at varying concentrations are incubated for 20-24 h.The next day, assays plates are taken out and equilibrated at RT for 20-30 minutes. Bright-Glo Luciferase Assay System is used to detect Luciferase production. After addition of Bright GLO detection reagent, the plates are incubated at RT for 20 minutes. The plates are read on an Envision plate reader to measure luminescence signal. The RLU signal is converted to POC relative to control and blank wells.
Measurement: IC50 = 235 nM (pChEMBL 6.630000114440918)
Descriptors: MW 564.67, ALogP 3.69, HBA 12, HBD 1, PSA 154.74, QED 0.3
Compound (SMILES): CN(CCc1ccccc1)c1nc(C(=O)NCC2CC2)cc(N2CCC(N(C)C)C2)n1
InChIKey: JAVRTYXUFDNXSM-UHFFFAOYSA-N
Target: N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (SINGLE PROTEIN), Homo sapiens
UniProt: Q6IQ20
Assay: Inhibition of full length human NAPE-PLD expressed in HEK293T cell lysate using PED6 as substrate preincubated for 30 mins followed by substrate addition and measured at 2 mins interval for 1 hr by tecan-plate reader analysis
Measurement: IC50 = 9549.93 nM (pChEMBL 5.019999980926514)
Descriptors: MW 422.58, ALogP 2.44, HBA 6, HBD 1, PSA 64.6, QED 0.67
Compound (SMILES): c1cc2cc(-c3ccc4oc(C5=NCCN5)cc4c3)[nH]c2cc1C1=NCCN1
InChIKey: YGJRBLKDKDPKDV-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99873
Assay: Inhibition of recombinant human His-tagged PRMT1 expressed in Escherichia coli BL21 (DE3) using biotin-labeled histone H4-20 as substrate incubated for 8 mins in presence of [3H]-SAM cofactor by scintillation proximity assay
Measurement: IC50 = 18700 nM (pChEMBL 4.730000019073486)
Descriptors: MW 369.43, ALogP 3.28, HBA 5, HBD 3, PSA 77.71, QED 0.52
Compound (SMILES): O=C(Nc1cncc(-c2cnc3[nH]nc(-c4cc5c(-c6cccnc6)cccc5[nH]4)c3c2)c1)C1CCC1
InChIKey: GDDQFUSNJNXLDU-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 485.55, ALogP 5.97, HBA 5, HBD 3, PSA 112.24, QED 0.28
Compound (SMILES): CCCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCCN)NC(=O)CCOCCOCCOCCOCCOCCOCCOCCOC)C(=O)NC(C)(C)C(=O)N[C@@H](Cc1ccc(Br)cc1)C(=O)O
InChIKey: LUIWSXCBCKMYNM-KBTGXBQNSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Activation of APJ receptor (unknown origin) expressed in Chem-5 cells assessed as stimulation of Ca2+ mobilization by Calcium 6-GF dye based fluorescence based assay
Measurement: EC50 = 8.128 nM (pChEMBL 8.09000015258789)
Descriptors: MW 2595.92
Compound (SMILES): CNC(=O)c1cccc(NC(=O)COc2ccc(C(=O)c3cc(Cl)ccc3Br)cc2)c1
InChIKey: NRWUEASWCKSIJP-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from human ERG stably expressed in HEK293 cell membranes assessed as unlabelled dofetilide IC50 at 10 uM measured after 60 mins by microbeta liquid scintillation counting method (Rvb = 9.1 to 11.7 nM)
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 501.76, ALogP 4.71, HBA 4, HBD 2, PSA 84.5, QED 0.46
Compound (SMILES): COc1cc2c(=O)c3c4ccc(C#N)cc4[nH]c3n(C(C)C)c2cc1N1CCN(C)CC1
InChIKey: ZUVNFZPWAOEUKH-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST tagged wild-type human ALK cytoplasmic domain (1058-1620 amino acids) expressed Sf9 cells pre-incubated for 30 mins before addition of Ulight-CKKSRGDYMTMQIG substrate and measured after 90 mins by fluorescence based assay
Measurement: IC50 = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 429.52, ALogP 3.85, HBA 6, HBD 1, PSA 77.29, QED 0.54
Compound (SMILES): CC(C)=CCC/C(C)=C/Cc1c(O)c(CC=C(C)C)c2c(c1O)C(=O)C1=CC3CC4C(C)(C)OC(C/C=C(\C)C(=O)O)(C3=O)C14O2
InChIKey: RCWNBHCZYXWDOV-WRXOINPPSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Binding affinity to EZH2 (unknown origin)
Measurement: Kd = 182 nM (pChEMBL 6.739999771118164)
Descriptors: MW 630.78, ALogP 7.27, HBA 7, HBD 3, PSA 130.36, QED 0.18
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](C(=O)NCCCF)[C@@H](O)[C@H]1O
InChIKey: VEXAKFSPTGBXJQ-QRIDJOKKSA-N
Target: Endoplasmin (SINGLE PROTEIN), Homo sapiens
UniProt: P14625
Assay: Displacement of FITC-geldanamycin from GRP94 (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: Kd = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 340.32, ALogP -1.5, HBA 9, HBD 4, PSA 148.41, QED 0.48
Compound (SMILES): O=C(CCN1CCC2c3ccccc3NC2C1)Oc1ccc(/C=C2\CCn3c2nc2ccccc2c3=O)cc1
InChIKey: NKGAOXISUWKUFF-ZBJSNUHESA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocytes AChE by Ellman's method
Measurement: IC50 = 0.93 nM (pChEMBL 9.029999732971191)
Descriptors: MW 518.62, ALogP 4.92, HBA 7, HBD 1, PSA 76.46, QED 0.3
Compound (SMILES): Cc1ccc(C(=O)Nc2cccc(OC(F)(F)F)c2)cc1-n1cc(-c2cncn2C)nn1
InChIKey: QWPCZUKJTQIWDU-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 142 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z601
Assay: Agonist activity at human GPR142 receptor expressed in HEK293 cells assessed as increase in IP1 to accumulation incubated for 60 mins by HTRF assay
Measurement: EC50 = 0.21 nM (pChEMBL 9.680000305175781)
Descriptors: MW 442.4, ALogP 4.13, HBA 7, HBD 1, PSA 86.86, QED 0.5
Compound (SMILES): O=C(O)CC1CC(=O)N1C(=O)NCc1ccccc1
InChIKey: XTNLRPMBRFOVIZ-UHFFFAOYSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Agonist activity at alphaVbeta3 in human SK-MEL-24 cells assessed as increase in cell adhesion to fibronectin pre-incubated for 30 mins before fibronectin and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 262.26, ALogP 0.97, HBA 3, HBD 2, PSA 86.71, QED 0.79
Compound (SMILES): CC1(C)C(=O)Nc2nc(-n3nc(Cc4c(F)ccc(F)c4F)c4ccccc43)nc(N)c21
InChIKey: NXIBFDKAAHJUKJ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 438.41, ALogP 3.64, HBA 6, HBD 2, PSA 98.72, QED 0.48
Compound (SMILES): O=C(Nc1ccc(S(=O)(=O)N2CCC[C@@H]2C(=O)NO)cc1)OCc1ccccc1
InChIKey: YHJQUVBJZRCTFG-QGZVFWFLSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of MMP2 (unknown origin) using Mca-Lys-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 5 min followed by substrate addition and measured for 30 mins by fluorescence based assay
Measurement: Ki = 2.16 nM (pChEMBL 8.670000076293945)
Descriptors: MW 419.46, ALogP 2.09, HBA 6, HBD 3, PSA 125.04, QED 0.49
Compound (SMILES): COc1cc2nccc(Oc3ccc(C(=O)Nc4ccccn4)cc3)c2cc1NC(=O)C#CCCN1CCOCC1
InChIKey: KPZGJWPPVXZLDN-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) expressed in baculovirus system using fluorescein labeled PDGFR-tide substrate peptide preincubated for 60 mins followed by ATP addition and measured after 60 mins by IMAP assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 551.6, ALogP 4.35, HBA 8, HBD 2, PSA 114.91, QED 0.31
Compound (SMILES): Cc1oc([C@@H]2CC[C@@H](C)N(C(=O)c3ccccc3-n3nccn3)C2)nc1C(C)(C)O
InChIKey: BCWFFIRXHYZBQY-GDBMZVCRSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Antagonist activity at human OX1R expressed in CHO cells assessed as inhibition of orexin A-induced intracellular Ca2+ release by FLIPR assay
Measurement: IC50 = 815 nM (pChEMBL 6.090000152587891)
Descriptors: MW 409.49, ALogP 3.2, HBA 7, HBD 1, PSA 97.28, QED 0.71
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2ccc3[nH]c(C(=O)c4cc5cc(O)ccc5o4)cc3c2)no1
InChIKey: XDLPFNWFWDSNMJ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human FLT3 ITD mutant EAIYAAPFAKKK peptide as substrate in presence of 33P-gamma ATP by hotspot kinase assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 458.47, ALogP 5.78, HBA 6, HBD 4, PSA 133.39, QED 0.25
Compound (SMILES): C[C@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)[C@@H](N)Cc1ccccc1)[C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(N)=O
InChIKey: RHMALYOXPBRJBG-NWDBMMEWSA-N
Target: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: Agonist activity at NOP (unknown origin) expressed in HEK293 cell membranes co-expressing Gbeta1-RGFP protein assessed as induction of G protein activation incubated for 15 mins by BRET assay
Measurement: EC50 = 23.44 nM (pChEMBL 7.630000114440918)
Descriptors: MW 1381.61
Compound (SMILES): Cc1cccc2nc([C@@H]3CC4(CC4)CN3c3ncnc4[nH]cnc34)n(-c3ccccc3)c(=O)c12
InChIKey: DYLVFNHADYPTIY-IBGZPJMESA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of human full-length recombinant His-tagged PI3K p110delta/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 2 hrs by ADP-Glo luminescence assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 449.52, ALogP 4.09, HBA 7, HBD 1, PSA 92.59, QED 0.45
Compound (SMILES): C[C@H](NC(=O)Cn1nc2cccc(N3CCNCC3)n2c1=O)c1ccc(OC(F)(F)F)cc1
InChIKey: YJQAFSSYEUQZMD-AWEZNQCLSA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as increase in calcium flux by calcium 5 dye based FLIPR assay
Measurement: EC50 = 10 nM (pChEMBL 8)
Descriptors: MW 464.45, ALogP 1.68, HBA 8, HBD 2, PSA 92.9, QED 0.58
Compound (SMILES): CCNC(=S)NNC(=O)CSc1nc2ccccc2c(=O)n1CCc1ccccn1
InChIKey: PJTFRIRBVFGSRR-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX1 assessed as reduction in PGF2alpha production using arachidonic acid as substrate preincubated with enzyme for 5 mins followed by substrate addition and measured after 2 mins by colorimetric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 442.57, ALogP 1.64, HBA 7, HBD 3, PSA 100.94, QED 0.22
Compound (SMILES): Cc1cc(NC2=NC(=O)CS2)no1
InChIKey: BNXWXAJEMKYCOS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR-TK (unknown origin) relative to control
Measurement: IC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 197.22, ALogP 1.02, HBA 5, HBD 1, PSA 67.49, QED 0.73
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(N)=O)[C@@H](C)O
InChIKey: GUFUXNJWSBAVDU-DLCHSWNNSA-N
Target: Furin (SINGLE PROTEIN), Homo sapiens
UniProt: P09958
Assay: Inhibition of recombinant soluble human furin using pyroGlu-Arg-Thr-Lys-Arg-methyl-coumaryl-7-amide as substrate measured after 1 hr
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 1225.52
Compound (SMILES): COc1cc(C(=O)N/N=C/c2ccc(OC(=O)N(C)C)cc2)ccc1O
InChIKey: PALIUEBDNXQUME-YBFXNURJSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine chloride as substrate preincubated for 15 mins followed by substrate addition and measured after 4 mins by Ellman's method
Measurement: IC50 = 21860 nM (pChEMBL 4.659999847412109)
Descriptors: MW 357.37, ALogP 2.23, HBA 6, HBD 2, PSA 100.46, QED 0.63
Compound (SMILES): CCCCCNC(=O)n1cc(-c2ccc(F)c(C3CCN(C)CC3)c2)oc1=O
InChIKey: GGZPYDOTOBEPAF-UHFFFAOYSA-N
Target: Acid ceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q13510
Assay: Inhibition of human acid ceramidase using N-lauroyl ceramide incubated for 1 hr by LC/MS analysis
Measurement: IC50 = 1923 nM (pChEMBL 5.71999979019165)
Descriptors: MW 389.47, ALogP 3.8, HBA 5, HBD 1, PSA 67.48, QED 0.76
Compound (SMILES): CCC(=O)c1ccc(-c2cn(-c3ccc(CCN4CCc5cc(OC)c(OC)cc5C4)cc3)nn2)cc1NC(=O)c1ccc2c(n1)CCCC2
InChIKey: XBHKBDDBBJHPDK-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of human ABCG2 in human MCF7/Topo cells assessed as accumulation of substrate Hoechst 33345 stain measured after 2 hrs by fluorometric microplate reader assay
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 670.81, ALogP 6.67, HBA 9, HBD 1, PSA 111.47, QED 0.16
Compound (SMILES): Br.N=C(N)[Se]Cc1ccc(CN2C(=O)C(=O)c3cc(Br)ccc32)cc1
InChIKey: DJMMWIXOYIFBPE-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of ALDH1A1 (unknown origin) assessed as NADH formation using propionaldehyde as substrate
Measurement: IC50 = 333 nM (pChEMBL 6.480000019073486)
Descriptors: MW 451.18
Compound (SMILES): Cc1cc(F)cnc1N1CCN(C(=O)CCCc2cccc3ncccc23)CC1
InChIKey: OCECXOHPPIBWHP-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Antagonist activity at human recombinant muscarinic receptor M1 expressed in CHO-K1 cells assessed as EC80 acetylcholine-induced calcium flux incubated for 30 mins
Measurement: IC50 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 392.48, ALogP 3.75, HBA 4, HBD 0, PSA 49.33, QED 0.66
Compound (SMILES): O=C(c1ccc(-c2nc3ccccc3s2)o1)N(Cc1ccco1)Cc1ccco1
InChIKey: GBOFAXCTGHAAKG-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Displacement of [3H]-SB67404 from human orexin 1 receptor expressed in CHO cells incubated for 2 hrs by whole cell radioligand binding assay
Measurement: Ki = 3548.13 nM (pChEMBL 5.449999809265137)
Descriptors: MW 404.45, ALogP 5.58, HBA 6, HBD 0, PSA 72.62, QED 0.37
Compound (SMILES): CNC(=O)c1cccc(-c2cnc3[nH]cc(-c4cc(C#N)c(Cl)c(NS(C)(=O)=O)c4)c3c2)c1
InChIKey: DXCOOOSNZJTJIQ-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Inhibition of TNIK (unknown origin)
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 479.95, ALogP 4.15, HBA 5, HBD 3, PSA 127.74, QED 0.4
Compound (SMILES): NC(=O)c1cc(Cl)c2ccc(-c3ccc(CN4CCCC4)cc3)nn12
InChIKey: FKBZKZYPVUMLNM-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 (unknown origin)
Measurement: IC50 = 432.39 nM (pChEMBL 6.360000133514404)
Descriptors: MW 354.84, ALogP 3.35, HBA 4, HBD 1, PSA 63.63, QED 0.78
Compound (SMILES): CN(CCc1ccccc1)c1nc(C(=O)NCc2ccccc2)cc(N2CCOCC2)n1
InChIKey: YYBQKHNMTPWGNB-UHFFFAOYSA-N
Target: N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (SINGLE PROTEIN), Homo sapiens
UniProt: Q6IQ20
Assay: Inhibition of full length human NAPE-PLD expressed in HEK293T cell lysate using PED6 as substrate preincubated for 30 mins followed by substrate addition and measured at 2 mins interval for 1 hr by tecan-plate reader analysis
Measurement: IC50 = 23442.29 nM (pChEMBL 4.630000114440918)
Descriptors: MW 431.54, ALogP 2.92, HBA 6, HBD 1, PSA 70.59, QED 0.59
Compound (SMILES): Cc1cc2c(Nc3ccccc3S(=O)(=O)C(C)C)nc(Nc3cc(C)c(C4CCN(C)CC4)cc3OC(C)C)nc2[nH]1
InChIKey: FAPJXRFDCACRNM-UHFFFAOYSA-N
Target: NPM/ALK (Nucleophosmin/ALK tyrosine kinase receptor) (CHIMERIC PROTEIN), Homo sapiens
UniProt: P06748
Assay: Inhibition of NMP-ALK (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 2 to 3 days by Bright-Glo luciferase assay
Measurement: IC50 = 1298 nM (pChEMBL 5.889999866485596)
Descriptors: MW 590.79, ALogP 6.84, HBA 8, HBD 3, PSA 112.24, QED 0.19
Compound (SMILES): O=C(CS(=O)(=O)Nc1ccccc1)Nc1c2c(cc3c1CCC3)CCC2
InChIKey: KSNLDJYJRHNURS-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 in human PBMC cells assessed as inhibition of LPS and ATP-induced IL-1beta production
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 370.47, ALogP 3.04, HBA 3, HBD 2, PSA 75.27, QED 0.85
Compound (SMILES): O=C1C=CC2(C=C1)OCC(=O)N2c1nc(-c2cccc3ccccc23)nn1-c1ccccc1
InChIKey: NSWXPDNYWQZXRX-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of AURKA (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 434.46, ALogP 3.84, HBA 6, HBD 0, PSA 77.32, QED 0.49
Compound (SMILES): C=CC(=O)Nc1cc(Nc2nccc(-c3cn(C4COC4)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: QHMWSARDRXHJRH-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human N-terminal GST-tagged EGFR T790M/L858R double mutant using biotinylated TK peptide as substrate measured after 30 mins by HTRF assay
Measurement: IC50 = 0.95 nM (pChEMBL 9.020000457763672)
Descriptors: MW 541.66, ALogP 4.54, HBA 9, HBD 2, PSA 96.78, QED 0.27
Compound (SMILES): CN(c1ccccc1)c1cc[n+](Cc2ccccc2)c2cc(Cl)ccc12.[Br-]
InChIKey: KRBZLQWSZXWRBW-UHFFFAOYSA-M
Target: Choline kinase alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35790
Assay: Binding affinity to human CKalpha1 assessed as dissociation constant by spectroflurometry
Measurement: Kd = 890 nM (pChEMBL 6.050000190734863)
Descriptors: MW 359.88, ALogP 5.6, HBA 1, HBD 0, PSA 7.12, QED 0.43
Compound (SMILES): Cc1cc(-c2ncnc3[nH]ccc23)ccc1CNC(=O)c1ccc(C(C)(C)C)cc1
InChIKey: KGJGITMOPYWSNC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of recombinant human full-length N-terminal His6-tagged BTK expressed in baculovirus infected Sf21 insect cells using fluorescein-labeled polyGAT peptide substrate measured after 30 mins by TR-FRET assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 398.51, ALogP 5.16, HBA 3, HBD 2, PSA 70.67, QED 0.5
Compound (SMILES): Cc1ccc(COc2nc(N3CCC[C@@H](CC(=O)O)C3)ccc2C(=O)NC2CCCCC2)cc1
InChIKey: WHHPUCFMIVQSED-NRFANRHFSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H mutant (unknown origin) using alpha-ketoglutarate and NADPH incubated for 30 mins by fluorescence based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 465.59, ALogP 4.72, HBA 5, HBD 2, PSA 91.76, QED 0.59
Compound (SMILES): CC(C)(C)NS(=O)(=O)c1cccc2c(NC(=O)C(Cc3ccccc3)NC(=O)c3ccccc3)cccc12
InChIKey: GIXYSOPAEGHVQN-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of USP30 (unknown origin)
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 529.66, ALogP 4.9, HBA 4, HBD 3, PSA 104.37, QED 0.3
Compound (SMILES): O=C(Nc1ccc(N2CCC(O)CC2)nc1)c1n[nH]c2ccc(-c3cncc(CN4CCCCC4)c3)cc12
InChIKey: HYSPWTPOQIWRHX-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 511.63, ALogP 4.22, HBA 7, HBD 3, PSA 110.27, QED 0.36
Compound (SMILES): Cc1cc([C@H]2CC[C@H](c3nnc4n3-c3ccc(Br)cc3CCC4)CC2)no1
InChIKey: UPNVUOYNFOUGKU-SHTZXODSSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Displacement of [3H]AVP from human V1a receptor expressed in 1132N1 cells assessed as dissociation constant by radioligand binding assay
Measurement: Ki = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 427.35, ALogP 5.26, HBA 5, HBD 0, PSA 56.74, QED 0.56
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nc2ccc(F)cn2c1-c1cccc(S(C)(=O)=O)c1
InChIKey: TYLDIOXQNAOHRU-LBPRGKRZSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant full length N-terminal polyHis-tagged PI3K p110beta/p85alpha (unknown origin) expressed in baculovirus infected Sf9 cells using PIP2 as substrate in presence of ATP incubated for 20 mins by Alphascreen assay
Measurement: IC50 = 5510 nM (pChEMBL 5.260000228881836)
Descriptors: MW 451.49, ALogP 2.96, HBA 9, HBD 2, PSA 139.06, QED 0.47
Compound (SMILES): O=S(=O)(/C=C/c1ccc(Cl)nc1)c1ccc(F)cc1
InChIKey: PXXLNUATIRHBOO-BQYQJAHWSA-N
Target: Nuclear factor erythroid 2-related factor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16236
Assay: Activation of Nrf2 (unknown origin) expressed in human U2OS cells co-expressing Keap1 assessed as increase in Nrf2 nuclear translocation incubated for 6 hrs under dark condition by pathhunter assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 297.74, ALogP 3.32, HBA 3, HBD 0, PSA 47.03, QED 0.64
Compound (SMILES): Cn1c(C(=O)Nc2cccc3c2N(Cc2ccc(OCc4ccc(C(N)=O)cc4)cc2)CCC3)cc2sccc21
InChIKey: ISZPZXCGJWMRNZ-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of human recombinant LSD1 using fluorogenic ADHP based substrate preincubated for 30 mins followed by substrate addition measured after 10 mins by horseradish peroxidase coupled fluorescence assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 550.68, ALogP 6.12, HBA 6, HBD 2, PSA 89.59, QED 0.24
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2cccc3cccnc23)CC1
InChIKey: GQUKVOGAZWDTMK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from human 5-HT1A receptor stably expressed in CHO-K1 cell membranes measured after 60 mins by Microbeta2 scintillation counting method
Measurement: Ki = 0.06026 nM (pChEMBL 10.220000267028809)
Descriptors: MW 459.92, ALogP 4.64, HBA 4, HBD 1, PSA 54.46, QED 0.52
Compound (SMILES): COc1cccc(-c2nc(C(=O)OCc3cccnc3)c(C)[nH]2)c1
InChIKey: KMRVKAXRRAJLOD-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Displacement of [3H]-SB67404 from human orexin 1 receptor expressed in CHO cells incubated for 2 hrs by whole cell radioligand binding assay
Measurement: Ki = 14791.08 nM (pChEMBL 4.829999923706055)
Descriptors: MW 323.35, ALogP 3.15, HBA 5, HBD 1, PSA 77.1, QED 0.73
Compound (SMILES): CCc1nccc2cc(Nc3n[nH]c4cccnc34)ccc12
InChIKey: LWNMUAQSSXQMHE-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14833
Assay: Metabotropic Glutamate Receptor Activity: The disclosed compounds and compositions can be evaluated for their ability to act as a potentiator of metabotropic glutamate receptor activity, in particular mGluR4 activity, by any suitable known methodology known in the art. For example, Chinese Hamster Ovary (CHO) cells transfected with human mGluR4 or HEK cells co-transfected with rat mGluR4 and the G-protein regulated Inwardly Rectifying Potassium channel (GIRK) were plated in clear bottom assay plates for assay in a Hamamatsu FDSS Fluorometric Plate Reader. The cells were loaded with either a Ca2+-sensitive fluorescent dye or the thallium responsive dye and the plates were washed and placed into a suitable kinetic plate reader. For human mGluR4 assays, a fluorescence baseline was established for 3-5 seconds, the disclosed compounds were then added to the cells, and the response in cells was measured. Approximately two and a half minutes later, a concentration of mGluR4 orthosteric agonist (e.g. glutamate or L-AP4) eliciting approximately 20% (EC20) of the maximal agonist response was added to the cells, and the response was measured. Two minutes later, a concentration of mGluR4 agonist (e.g. glutamate or L-AP4) eliciting 80% (EC80) of the maximal agonist response was added to the cells, and the response was measured. For rat mGluR4/GIRK experiments, a baseline was established for approximately five seconds, disclosed compounds were added, and either an EC20 or EC80 concentration of agonist was added approximately two and one half minutes later. Potentiation of the agonist response of mGluR4 by the disclosed compounds was observed as an increase in response to the EC20 concentration of agonist in the presence of compound compared to the response to agonist in the absence of compound. Similarly, antagonism of the agonist response of mGluR4 by the disclosed compounds was observed as a decrease in response to the EC80 concentration of agonist in the presence of compound compared to the response to agonist in the absence of compound.
Measurement: EC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 289.34, ALogP 3.81, HBA 4, HBD 2, PSA 66.49, QED 0.6
Compound (SMILES): Cc1ccc(Oc2ccc(Nc3ncnc4cc(OCCCN5CCOCC5)c(NC(=O)c5cc([N+](=O)[O-])ccc5F)cc34)cc2Cl)cn1
InChIKey: KESYYPPAVUQGCO-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant human N-terminal GST tagged EGFR d746-750 mutant (669 to 1210 residues) expressed in insect expression system using peptide as substrate incubated for 2 hrs followed by substrate addition and measured after 30 mins by TR-FRET assay
Measurement: IC50 = 419 nM (pChEMBL 6.380000114440918)
Descriptors: MW 688.12, ALogP 6.92, HBA 11, HBD 2, PSA 153.87, QED 0.08
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnc4n3CCC4)c(Cl)cn2)C1
InChIKey: OHJQYFCYYWSDGL-UONOGXRCSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of recombinant full length human N-terminal GST-fused CDK9 (1 to 372 residues)/His-tagged CyclinT1 (1 to 726 residues) expressed in baculovirus infected insect cells using FITC-X-GSRTPMY-NH2 as substrate preincubated for 10 mins followed by MgCl2 addition and measured after 90 mins in presence of 5 mM ATP by mobility shift assay
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 401.9, ALogP 3.18, HBA 5, HBD 2, PSA 88.91, QED 0.82
Compound (SMILES): COc1ccc(NC(=O)CC2COc3ccccc3C2)cc1Cl
InChIKey: ARWIUUOQIIJYSA-UHFFFAOYSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Allosteric inhibition of human wild-type full-length MALT1 (329 to 824 residues) protease activity using Ac-Leu-Arg-Ser-Arg Rh110-dPro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 331.8, ALogP 3.93, HBA 3, HBD 1, PSA 47.56, QED 0.92
Compound (SMILES): CCOc1ccc(-c2c(C(C)(C)O)oc(=O)c3ccccc23)cc1OC1CCCC1
InChIKey: FEEDBHIHBIWFMR-UHFFFAOYSA-N
Target: High affinity 3',5'-cyclic-AMP phosphodiesterase 7A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13946
Assay: Inhibition of recombinant PDE7A1 (130 to 482 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) using [3H]cAMP as substrate incubated for 15 mins by liquid scintillation method
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 408.49, ALogP 5.41, HBA 5, HBD 1, PSA 68.9, QED 0.59
Compound (SMILES): COc1cc(/C=C/C(=O)N2CCCCC2)ccc1OC(=O)N(c1ccccc1)c1ccccc1
InChIKey: FRTYPMGQTQZTSS-FBMGVBCBSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A
Measurement: IC50 = 46200 nM (pChEMBL 4.329999923706055)
Descriptors: MW 456.54, ALogP 6.06, HBA 4, HBD 0, PSA 59.08, QED 0.42
Compound (SMILES): N#Cc1cccc([C@H](CC(=O)O)C(=O)N2CC[C@@H](CCc3ccc4c(n3)NCCC4)C2)c1
InChIKey: LKLFMSIRSSIJBV-VGSWGCGISA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of integrin alphavbeta3 (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 432.52, ALogP 3.35, HBA 5, HBD 2, PSA 106.32, QED 0.69
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(C(C)(C)C)cc2c1C(=O)Nc1ccc(C(=O)O)cc1F
InChIKey: OCYFYABJSPCSCT-UHFFFAOYSA-N
Target: Prostaglandin F2-alpha receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43088
Assay: In Vitro Test of Inhibition of Human FP Receptor Activity (B-1A): For the characterization of test substances in respect of FP antagonism, PGF2α-induced calcium flux in FP-expressing CHEM1 cells (Millipore, HTS093C) was used.3000 cells in 25 μl of full medium [DMEM F12, 10% FCS, 1.35 mM sodium pyruvate, 20 mM HEPES, 4 mM GlutaMAX, 2% sodium bicarbonate, 1% Pen/Strep, 1% 100× non-essential amino acids] are sown per well of a 384 multititer plate (from Greiner, TC plate, black with clear base) and incubated at 37° C./5% CO2 for 24 hours. Prior to the measurement, the medium is replaced by 30 μl of Fluo-8 AM loading buffer [calcium-free Tyrode (130 mM NaCl, 5 mM KCl, 20 mM HEPES, 1 mM MgCl2, 4.8 mM NaHCO3, pH 7.4), 2 mM CaCl2, 1× SmartBlock (from CANDOR Bioscience GmbH), 4.5 mM Probenecid, 5 μM Fluo-8 AM, 0.016% Pluronic, 0.04% Brilliant black] and incubated at 37° C./5% CO2 for 30 minutes. The test substance is prepared in DMSO in various concentrations as a dose-response curve (starting concentration 10 mM, dilution factor 3.16) and prediluted 1:50 with calcium-free Tyrode/2 mM CaCl2. 10 μl of the prediluted substance solution are added to the Fluo-8-laden cells and incubated at 37° C./5% CO2 for 10 minutes. The FP receptor is activated by adding 20 μl of 3 nM (final concentration) PGF2α in calcium-free Tyrode/2 mM CaCl2/0.04% Brilliant black, and the calcium flux is determined by measuring the fluorescence at ex. 470 nm/em. 525 nm in a fluorescence measuring instrument (FLIPR Tetra, Molecular Devices) for 120 seconds.
Measurement: IC50 = 131 nM (pChEMBL 6.880000114440918)
Descriptors: MW 456.52, ALogP 6.6, HBA 3, HBD 2, PSA 79.29, QED 0.36
Compound (SMILES): O=C1N=C(NCc2ccc(O)cc2)S/C1=C\c1ccc(-c2ccc(C(F)(F)F)cc2)o1
InChIKey: VJLAKUDODUOYBK-ODLFYWEKSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of PIM1 (unknown origin) by coupled kinetic assay
Measurement: IC50 = 53.7 nM (pChEMBL 7.269999980926514)
Descriptors: MW 444.43, ALogP 5.43, HBA 5, HBD 2, PSA 74.83, QED 0.53
Compound (SMILES): O=C(O)C[C@@H]1CCCN(c2ccc(C(=O)NC3CCCCC3)c(OCC3CCCCC3)n2)C1
InChIKey: HPXWECDTINZFEY-FQEVSTJZSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H mutant (unknown origin) using alpha-ketoglutarate and NADPH incubated for 30 mins by fluorescence based assay
Measurement: IC50 = 9700 nM (pChEMBL 5.010000228881836)
Descriptors: MW 457.62, ALogP 4.79, HBA 5, HBD 2, PSA 91.76, QED 0.58
Compound (SMILES): Fc1ccccc1-c1nccc2[nH]c(-c3n[nH]c4cnc(-c5cncc(CN6CCCC6)c5)cc34)cc12
InChIKey: DSGKKKTWVMQQSA-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 489.56, ALogP 5.97, HBA 5, HBD 2, PSA 86.38, QED 0.31
Compound (SMILES): CS(=O)(=O)N1CCN(Cc2cc3c(N4CCOCC4)nc(-c4ccc(NC(=O)Nc5ccc(F)cc5)cc4)nn3c2)CC1
InChIKey: ZOEXBICCWJEIHU-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of human PI3Kalpha using PIP2 as substrate in presence of ATP measured after 30 mins by HTRF assay
Measurement: IC50 = 105.3 nM (pChEMBL 6.980000019073486)
Descriptors: MW 608.7, ALogP 3.09, HBA 9, HBD 2, PSA 124.41, QED 0.33
Compound (SMILES): CC[C@@H]1c2nncn2-c2cnc(Nc3ccc(C(=O)NC4CCN(C)CC4)cc3OC)nc2N1Cc1ccco1
InChIKey: YLWCWWXFUDMWQL-JOCHJYFZSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of full length human PLK1 using casein as substrate incubated for 40 mins in presence of [gamma-33P]-ATP by radiometric assay
Measurement: IC50 = 6375 nM (pChEMBL 5.199999809265137)
Descriptors: MW 543.63, ALogP 3.7, HBA 11, HBD 2, PSA 126.47, QED 0.34
Compound (SMILES): C[C@H]1NC(=O)[C@H](CCCCN)NC(=O)CCSCc2cc(F)cc(c2)CSC[C@@H](C(N)=O)NC(=O)[C@]2(C)CCCN2C(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2c[nH]c3ccc(F)cc23)NC(=O)[C@H](Cc2c[nH]c3ccc(F)cc23)NC1=O
InChIKey: YGYMSEGRFBIXIG-RNFNLGEGSA-N
Target: Proprotein convertase subtilisin/kexin type 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NBP7
Assay: Inhibition of AlexaFluor647-tagged cyclic peptide binding to avi-tagged-biotinylated human PCSK9 measured after 2 hrs by Lance Streptavidin Europium based FRET assay
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 1408.64
Compound (SMILES): O=C(Nc1ccc(C(F)(F)F)c(F)c1)NC1CCN(C(=O)C2CC2)CC1
InChIKey: IIGBRXYVEOEPDV-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: FRET-displacement assay: FRET assays to determine Ki for the compounds of Table I were carried out as described previously (Lee et al. Analytical Biochemistry 434 (2013) 259-268). In order to prevent leaching of fluorescence impurities from the plastic tube and non-specific binding to sEH inhibitors, the inhibitor stock solution (10 mM, DMSO) was stored in glass vials. In addition, sEH was diluted to desired concentration (20 nM) with sodium phosphate buffer (PB) (100 mM sodium phosphate, pH 7.4, 0.01% gelatin) to avoid loss of protein from non-specific binding to the cuvette surface. All buffer used in this assay was filtered by sterilized filtration unit (Millipore Durapore PVDF Membrane, pore size: 0.22 um).Measurement in 96-Well PlatesAll the measurement for FRET-based displacement assay in 96-well plate format were done in TECAN Infinite M1000 Pro 96 well fluorescence plate reader.Pre-Treatment of 96-Well PlateIn order to prevent non-specific binding of sEH or inhibitor on the 96-well plate, the 96 well plates were pre-incubated with PB with 0.1% gelatin overnight at rt. The gelatin coats the plate and prevents non-specific binding of sEH and sEH inhibitors to the plate. The buffer was discarded and the plate was dried before use.Assay ProcedureThe sEH stock was diluted to the desired concentration (20 nM) by PB (100 mM sodium phosphate, 0.1% gelatin, pH 7.4). ACPU (one equivalent to sEH, 10 mM, Ethanol) was added to the sEH solution and was incubated for 2 h at rt. The sEH-ACPU mixture (20 nM, 100 mM sodium phosphate, 0.1% gelatin, pH 7.4, 150 uL) was added to each well.The baseline fluorescence (F0) (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured after the z-position and gain were optimized automatically by the fluorometers. The z and gain value was noted and will be used for the later fluorescent measurement. Because DMSO has been known to quench fluorescence. 1% DMSO in PB was served as a control (FDMSO). The desired concentration of inhibitors which is the concentration that 100% of sEH was bound to inhibitor, was added at the first well and was further diluted by 2-fold across the rest of the wells. Based on our study, 12 datum points which correspond to 12 different concentrations of the inhibitor, provide significant data to calculate the accurate Ki for the inhibitors. The samples were incubated at 30° C. for 1.5 h. Then, the fluorescence (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured using the z-position and gain values that previously obtained.
Measurement: Ki = 0.38 nM (pChEMBL 9.420000076293945)
Descriptors: MW 373.35, ALogP 3.37, HBA 2, HBD 2, PSA 61.44, QED 0.8
Compound (SMILES): CC(C)(N)CN(C1CCC1)C1(c2cccc(C(F)(F)F)c2)CC1
InChIKey: JUZLGOJRWYZRGA-UHFFFAOYSA-N
Target: Intermediate conductance calcium-activated potassium channel protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15554
Assay: Inhibition of Kca3.1 in human erythrocytes
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 326.41, ALogP 4.29, HBA 2, HBD 1, PSA 29.26, QED 0.87
Compound (SMILES): OC[C@H]1O[C@@H](c2cc(Cc3cc4ccccc4s3)c(Cl)cc2O)[C@H](O)[C@@H](O)C1(F)F
InChIKey: URGFAONHCWSEQV-FUMNGEBKSA-N
Target: Sodium/glucose cotransporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13866
Assay: Inhibition of human SGLT1 expressed in CHO cells assessed as reduction in [14C]-methyl-alpha -D-glucopyranoside accumulation
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 456.89, ALogP 3.64, HBA 6, HBD 4, PSA 90.15, QED 0.48
Compound (SMILES): C[C@@H]1Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3(C)CN(CCCF)C3)cn2)N1CC(F)(F)F
InChIKey: HVUZKCRFWNESKY-MWTRTKDXSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Induction of ERalpha degradation in human MCF7 cells assessed as decrease in ER-alpha level incubated for 18 to 24 hrs by Alexa fluor 488/Hoechst staining based immunofluorescence imaging analysis
Measurement: IC50 = 3.162 nM (pChEMBL 8.5)
Descriptors: MW 490.55, ALogP 4.7, HBA 5, HBD 2, PSA 60.08, QED 0.47
Compound (SMILES): Cc1c(-c2ccccc2)nc2ccc(Br)cc2c1CNc1ccc(C(=O)O)cc1F
InChIKey: XYXZUMVOWFXLHT-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 10 mins in presence of NADPH generating system by LC-MS/MS analysis
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 465.32, ALogP 6.42, HBA 3, HBD 2, PSA 62.22, QED 0.36
Compound (SMILES): COc1cc(/C=c2\sc3nc4ccc(NC(C)=O)cc4n3c2=O)cc(OC)c1OC
InChIKey: UOHQSYSWVJOIOT-NVMNQCDNSA-N
Target: DNA topoisomerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11387
Assay: Inhibition of human topoisomerase-1 beta incubated for 2 hrs by ELISA
Measurement: IC50 = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 425.47, ALogP 2.44, HBA 8, HBD 1, PSA 91.16, QED 0.53
Compound (SMILES): C=CC(=O)Nc1ccc(-c2cc(Nc3cnn(CCOC)c3)ncn2)cc1
InChIKey: MVKOIQROLYNKGI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human GST-tagged JAK3 cytoplasmic domain (781 to 1124 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 364.41, ALogP 2.85, HBA 7, HBD 2, PSA 93.96, QED 0.6
Compound (SMILES): O=C(Nc1ccccc1F)N1CCN(c2ccnc(Cl)n2)CC1
InChIKey: SPPREJSGHSHQMF-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Antagonist activity at human TRPV1 assessed as inhibition of capsaicin-induced channel activation
Measurement: IC50 = 787 nM (pChEMBL 6.099999904632568)
Descriptors: MW 335.77, ALogP 2.62, HBA 4, HBD 1, PSA 61.36, QED 0.86