lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@@H]1C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@H](Cc2ccccc2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@H](C(N)=O)CSCc2cccc(c2)CSC1(C)C
InChIKey: GUWAZMLXUQIQKT-SIXPOYHZSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Displacement of [125I]NDP-alpha-MSH from human MC5R expressed in HEK293 cells by competitive binding assay
Measurement: IC50 = 93.5 nM (pChEMBL 7.03000020980835)
Descriptors: MW 1135.43
Compound (SMILES): COc1cc2c(cc1OCCN1CCCCC1)C(=O)C(Cc1cccnc1)C2
InChIKey: OUWASZTUNZDMFL-UHFFFAOYSA-N
Target: cGMP-dependent 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00408
Assay: Inhibition of PDE2A (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 380.49, ALogP 3.55, HBA 5, HBD 0, PSA 51.66, QED 0.74
Compound (SMILES): COc1cc(S(N)(=O)=O)ccc1OCCC(N)C1COc2ccccc2O1
InChIKey: KOIYEFLKONFTEX-UHFFFAOYSA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Inhibition of human recombinant CA5A assessed as inhibition constant pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 456 nM (pChEMBL 6.340000152587891)
Descriptors: MW 394.45, ALogP 1.28, HBA 7, HBD 2, PSA 123.1, QED 0.72
Compound (SMILES): C#CCN(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N2CCC(C(=O)OC)CC2)cc1
InChIKey: FMBRAYUCAAUXJJ-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition of recombinant human DHFR expressed in Escherichia coli BL21 (DE3) cells using dihydrofolate as substrate in presence of NADPH by spectrophotometric analysis
Measurement: IC50 = 78000 nM (pChEMBL 4.110000133514404)
Descriptors: MW 474.53, ALogP 1.25, HBA 10, HBD 2, PSA 153.45, QED 0.39
Compound (SMILES): CCn1c(CO)nn(-c2nc(O[C@@H](C)C(F)(F)F)c(C(=O)Nc3c(C)ccnc3Cl)cc2F)c1=O
InChIKey: XEDJGCIOZDHXOR-JTQLQIEISA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in HEK293 cells by radioligand binding assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 518.86, ALogP 3.02, HBA 9, HBD 2, PSA 124.16, QED 0.36
Compound (SMILES): COc1ccc(C2(C(=O)N3CS(=O)(=O)C[C@@H]3C(=O)Nc3cccc4[nH]ncc34)CCCC2)cc1
InChIKey: VWZAAFMUYDNGED-OAQYLSRUSA-N
Target: Histone acetyltransferase KAT7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95251
Assay: Inhibition of MYST2 (unknown origin) using biotinylated H4 (1 to 25)-GSGSK peptide as substrate incubated for 1 hr by AlphaLISA assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 482.56, ALogP 2.61, HBA 6, HBD 2, PSA 121.46, QED 0.58
Compound (SMILES): O=C1NC(NC2CCNCC2)=N/C1=C\c1ccc2c(c1)OCO2
InChIKey: QGGNWMQODZFHNG-GHXNOFRVSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of GST-fused human recombinant DYRK1A expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 314.35, ALogP 0.58, HBA 6, HBD 3, PSA 83.98, QED 0.7
Compound (SMILES): COc1ccc(Cc2nnc(Cc3c[nH]c4cc(F)ccc34)n2CCCc2c[nH]cn2)cc1
InChIKey: LYMDSJLOXOXMHN-UHFFFAOYSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Displacement of [125I]-Tyr-SRIF 14 from SST3 receptor (unknown origin) expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 444.51, ALogP 4.44, HBA 5, HBD 2, PSA 84.41, QED 0.35
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(Cl)c(O[C@@H]3CO[C@H]4[C@@H]3OC[C@H]4OC)n2)ccc1N(C)CCN(C)C
InChIKey: MXXJXRACSRJBKS-OHUMZHCVSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1
Measurement: IC50 = 4728 nM (pChEMBL 5.329999923706055)
Descriptors: MW 533.03, ALogP 2.56, HBA 10, HBD 2, PSA 110.31, QED 0.42
Compound (SMILES): Fc1ccc2c(Cc3nnc(Cc4cccc(C(F)(F)F)c4)n3CCCc3c[nH]cn3)c[nH]c2c1
InChIKey: HRMZYZYVRKSGFD-UHFFFAOYSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Displacement of [125I]-Tyr-SRIF 14 from SST3 receptor (unknown origin) expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki = 1613 nM (pChEMBL 5.789999961853027)
Descriptors: MW 482.49, ALogP 5.45, HBA 4, HBD 2, PSA 75.18, QED 0.29
Compound (SMILES): CCC(CC)CNC1CCN(C(=O)Nc2cc(Oc3ccncc3)cc(Oc3ccc(F)cc3)c2)CC1
InChIKey: JLZBHJGZPHUQKG-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Binding affinity to S1PR5 (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis
Measurement: Kd > 100 nM (pChEMBL 7)
Descriptors: MW 506.62, ALogP 6.83, HBA 5, HBD 2, PSA 75.72, QED 0.32
Compound (SMILES): FC(F)(F)c1cccc(COC2CCN(Cc3cc4ccc(Cl)cc4[nH]3)CC2)c1
InChIKey: UAYVZHLRDFXTFC-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 211 nM (pChEMBL 6.679999828338623)
Descriptors: MW 422.88, ALogP 6.02, HBA 2, HBD 1, PSA 28.26, QED 0.54
Compound (SMILES): COc1ccc(Oc2ccc(CN(Cc3ccccc3)Cc3cnc4nc(N)nc(N)c4n3)cc2)cc1
InChIKey: OBAQLSSSQKPYLE-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition of recombinant human DHFR expressed in Escherichia coli BL21 (DE3) cells using dihydrofolate as substrate in presence of NADPH by spectrophotometric analysis
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 493.57, ALogP 4.59, HBA 9, HBD 2, PSA 125.3, QED 0.3
Compound (SMILES): Cn1cc(NC(=O)c2cc(C(=O)c3c(Cl)ccc(Cl)c3F)c[nH]2)cn1
InChIKey: LIEUQFMVFKJKHX-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Binding affinity to wild-type human partial length CSF1R (I564 to S939 residues) expressed in bacterial expression system by Kinomescan assay
Measurement: Kd = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 381.19, ALogP 3.68, HBA 4, HBD 2, PSA 79.78, QED 0.53
Compound (SMILES): NS(=O)(=O)c1ccc(CCN2C(=O)c3ccc(C(=O)O)cc3C2=O)cc1
InChIKey: GYAMADYYIZTRHJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human recombinant CA9 assessed as inhibition constant incubated for 10 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 54.1 nM (pChEMBL 7.269999980926514)
Descriptors: MW 374.37, ALogP 0.87, HBA 5, HBD 2, PSA 134.84, QED 0.75
Compound (SMILES): N#Cc1ccc(S[C@H]2O[C@H](CO)[C@H](O)[C@H](n3cc(-c4cc(F)c(F)c(F)c4)nn3)[C@H]2O)cc1Cl
InChIKey: RXISTOYAZFSXTN-OBJCFNGXSA-N
Target: Galectin-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56470
Assay: Binding affinity to C-terminal domain of human Galectin-4 assessed as dissociation constant by fluorescence polarization
Measurement: Kd = 191 nM (pChEMBL 6.71999979019165)
Descriptors: MW 512.9, ALogP 2.66, HBA 9, HBD 3, PSA 124.42, QED 0.45
Compound (SMILES): Cc1cc(N)c(S(N)(=O)=O)cc1C(=O)Nc1cc(F)c(F)c(F)c1
InChIKey: RLCJNRRDMJQHSR-UHFFFAOYSA-N
Target: Core antigen (SINGLE PROTEIN), Hepatitis B virus
UniProt: Q03732
Assay: Modulation of capsid assembly in HBV genotype B infected in human HepG2.2.15 cells assessed as inhibition of viral DNA replication
Measurement: EC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 359.33, ALogP 1.89, HBA 4, HBD 3, PSA 115.28, QED 0.57
Compound (SMILES): CCn1c(CO)nn(-c2nc(O[C@@H](C)C(F)(F)F)c(C(=O)Nc3c(C)cnc(OC)c3Cl)cc2F)c1=O
InChIKey: FJYNLQXYLQBCRQ-JTQLQIEISA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in HEK293 cells by radioligand binding assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 548.88, ALogP 3.03, HBA 10, HBD 2, PSA 133.39, QED 0.41
Compound (SMILES): O=C(Nn1c(=O)c(=O)[nH]c2cc(C(F)(F)F)c(F)cc21)c1ccccc1O
InChIKey: MCKOVZZCGOMMIB-UHFFFAOYSA-N
Target: Glutamate receptor ionotropic, kainate 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16478
Assay: Binding affinity to GluK5 receptor (unknown origin)
Measurement: Ki = 26400 nM (pChEMBL 4.579999923706055)
Descriptors: MW 383.26, ALogP 1.94, HBA 5, HBD 3, PSA 104.19, QED 0.46
Compound (SMILES): CC1(N)CCN(Cc2ccn3ncnc(Nc4cc(O)cc(Br)c4)c23)CC1
InChIKey: DBMRETDBROLHGL-UHFFFAOYSA-N
Target: Tau-tubulin kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6IQ55
Assay: Inhibition of TTBK2 (unknown origin)
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 431.34, ALogP 3.25, HBA 7, HBD 3, PSA 91.71, QED 0.59
Compound (SMILES): CCCCCCCCCCSC[C@H](NC(=O)[C@H](CO)NC(=O)CN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)C(C)C
InChIKey: YOMFCYWNOCWSBC-QUHOFJIWSA-N
Target: Appetite-regulating hormone (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBU3
Assay: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay
Measurement: EC50 = 1.622 nM (pChEMBL 8.789999961853027)
Descriptors: MW 3401.06
Compound (SMILES): C=CC(=O)N1CCC(C(=O)O)(c2ccc(Cl)cc2)CC1
InChIKey: BBISGFJIKYHGHR-UHFFFAOYSA-N
Target: CXXC-type zinc finger protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2H0
Assay: Inhibition of GST-tagged human IDAX (130 to 181 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay
Measurement: IC50 = 33000 nM (pChEMBL 4.480000019073486)
Descriptors: MW 293.75, ALogP 2.47, HBA 2, HBD 1, PSA 57.61, QED 0.87
Compound (SMILES): COc1cc(OC)c(Cl)c(Nc2ncccc2-c2ncnc(Nc3cnn(C4CCN(C(C)C)CC4)c3)n2)c1Cl
InChIKey: QPGRMRIBWAFOOC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 V561M mutant (unknown origin) by radiometric kinase activity assay
Measurement: IC50 = 262.5 nM (pChEMBL 6.579999923706055)
Descriptors: MW 584.51, ALogP 5.99, HBA 11, HBD 2, PSA 115.14, QED 0.24
Compound (SMILES): NC(=O)c1ccc(C(=O)OC(CCCN2CCC(O)(c3ccc(Cl)cc3)CC2)c2ccc(F)cc2)cc1
InChIKey: WLSKNVLLQXLXOI-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]-U69593 from Dunkin-Hartley guinea pig brain membrane kappa opioid receptor incubated for 30 mins by liquid scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 525.02, ALogP 5.24, HBA 5, HBD 2, PSA 92.86, QED 0.37
Compound (SMILES): Cc1nc(NC(=O)NC(=O)C(C)C)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: LDFPZTVJHCRSKV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) measured by spectrophotometric analysis
Measurement: IC50 > 3300 nM (pChEMBL 5.480999946594238)
Descriptors: MW 394.44, ALogP 3.28, HBA 7, HBD 2, PSA 111.03, QED 0.69
Compound (SMILES): c1cc2ccc(CN3CCCCC3)ccc-2c1
InChIKey: XYMIGUUUODRJDC-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate preincubated with compound followed by NADPH addition by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 225.33, ALogP 3.78, HBA 1, HBD 0, PSA 3.24, QED 0.75
Compound (SMILES): O=C1NC(=O)/C(=C\c2ccc(OCC(=O)N3N=C(c4ccccc4)CC3c3ccc(Cl)c(Cl)c3)cc2)S1
InChIKey: JTPZHEMUSATIFE-WYMPLXKRSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of C-terminal His-tagged recombinant human HDAC3 (1 to 428 residues)/N-terminal GST-tagged recombinant human NCoR2 (395 to 489 residues) co-expressed in baculovirus infected Sf9 cells using Boc-Lys(acetyl)-AMC as substrate incubated for 30 mins by fluorescence assay
Measurement: IC50 = 9100 nM (pChEMBL 5.039999961853027)
Descriptors: MW 552.44, ALogP 6.07, HBA 6, HBD 1, PSA 88.07, QED 0.38
Compound (SMILES): COc1cc(C(=O)c2csc(-c3ccc(NCC(=O)Nc4ccccc4N)cc3)n2)cc(OC)c1OC
InChIKey: LZQWFCVURBGBJM-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of full length C-terminal his-tagged human recombinant HDAC8 (142 to 143 residues) expressed in baculovirus in Sf9 insect cells using Ac-Leu-Gly-Lys (Tfa)-AMC as substrate pretreated for 5 mins followed by substrate addition and measured after 30 mins
Measurement: IC50 = 9110 nM (pChEMBL 5.039999961853027)
Descriptors: MW 518.6, ALogP 4.7, HBA 9, HBD 3, PSA 124.8, QED 0.2
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)C/C=C(\F)[C@@H](N)Cc1ccc(O)cc1)C(N)=O
InChIKey: JRQWLWZTKLOPSQ-ICXILOJFSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P32300
Assay: Agonist activity at FLAG-tagged mouse delta opioid receptor expressed in human HEK293 cells assessed as inhibition of forskolin stimulated cAMP production preincubated for 20 mins followed by forskolin stimulation and measured after 15 mins by GloSensor assay
Measurement: IC50 = 46.6 nM (pChEMBL 7.329999923706055)
Descriptors: MW 555.65, ALogP 1.37, HBA 6, HBD 6, PSA 176.64, QED 0.19
Compound (SMILES): CCCC[C@@H]1NC(=O)[C@@H]2CSCc3ccccc3CSC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@H](Cc3cnc[nH]3)NC(=O)CNC1=O)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c3ccccc13)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: FIPGSBWOMGALGM-WPTGWSDQSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Antagonist activity at human MC4R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay
Measurement: EC50 = 1.38 nM (pChEMBL 8.859999656677246)
Descriptors: MW 2159.55
Compound (SMILES): O=C(NO)c1ccc(/C=N/NC(=O)c2cc(N3CCOCC3)nc(-c3cccc(O)c3)n2)cc1
InChIKey: QIXCKSONTDMMTH-ZVHZXABRSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of HDAC11 (unknown origin)
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 462.47, ALogP 1.57, HBA 9, HBD 4, PSA 149.27, QED 0.24
Compound (SMILES): CCc1nc(NC(=O)NC(=O)C(C)(C)C)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: URZFDLKDKFIRGI-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of N-terminal His-Glu-TEV-tagged MET (unknown origin) (1050 to 1360 residues) measured by spectrophotometric analysis
Measurement: IC50 > 3300 nM (pChEMBL 5.480999946594238)
Descriptors: MW 422.49, ALogP 3.93, HBA 7, HBD 2, PSA 111.03, QED 0.64
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](N)CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]2CSSC[C@H](NC(=O)[C@H](CCC(N)=O)NC2=O)C(=O)N2CCC[C@H]2C(=O)N2CCC[C@H]2C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)O
InChIKey: SZCLBSHELXLOEC-OXOGCWQMSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in CHO cells by Topcount beta counter analysis
Measurement: Ki = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 2969.59
Compound (SMILES): COc1cc(-c2cc3c(N[C@H]4CCN(C(=O)C5CCC5)C4)ncnc3s2)cnc1OC
InChIKey: XIPMIAQFOCCQEU-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in IgM stimulated human Raji cells incubated for 10 mins by AlphaLISA assay
Measurement: IC50 = 33.7 nM (pChEMBL 7.46999979019165)
Descriptors: MW 439.54, ALogP 3.58, HBA 8, HBD 1, PSA 89.47, QED 0.63
Compound (SMILES): COc1ccc(C2NCCc3c2[nH]c2ccc(F)cc32)c(OC)c1.Cl
InChIKey: UZUPBDVDHKDGQH-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5HT2B receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 97.72 nM (pChEMBL 7.010000228881836)
Descriptors: MW 326.37, ALogP 3.56, HBA 3, HBD 2, PSA 46.28, QED 0.77
Compound (SMILES): c1cc(CNc2ncc(-c3ccncc3)c3nncn23)c2c(c1)OCC2
InChIKey: ADDFHWGEAOKELS-UHFFFAOYSA-N
Target: Polycomb protein EED (SINGLE PROTEIN), Homo sapiens
UniProt: O75530
Assay: EED-H3K27Me3 Peptide Competition Binding Assay by AlphaScreen: To assess the compounds potency in the EED-H3K27Me3 competition binding assay, compounds were serially diluted 3-fold in DMSO to obtain a total of twelve concentrations. Then compounds at each concentration (75 nL of each) were transferred by Mosquito into a 384-well Perkin Elmer ProxiPlate 384 plus plates. 8 uL of solutions containing 30 nM EED (1-441)-His protein and 15 nM biotin-H3K27Me3 (19-33) peptide in the buffer (25 mM HEPES, pH 8, 0.02% Tween-20, 0.5% BSA) were added to the wells and then incubated with compound for 20 min. AlphaScreen detection beads mix was prepared immediately before use by mixing nickel chelate acceptor beads and streptavidin donor beads in a 1:1 ratio (Perkin Elmer, Product No. 6760619C/M/R) into the buffer described above. Then 4 μL of detection beads mix was added to the plate and incubate in the dark at the rt for 1 h. The final concentration of donor and acceptor beads was 10 μg/mL for each. Plates were read on EnVision (PerkinElmer) using the AlphaScreen setting adapted for optimal signal detection with a 615 nm filter, after sample excitation at 680 nm. The emission signal at 615 nm was used to quantify compounds inhibition. AlphaScreen signals were normalized based on the reading coming from the positive (maximum signal control) and negative controls (minimum signal control) to give percentage of activities left. The data were then fit to a dose response equation using the program Helios (Novartis) to get the IC50 values. Helios is a Novartis in-house assay data analysis software using the methods described by Normolle, D. P., Statistics in Medicine, 12:2025-2042 (1993); Formenko, I. et al, Computer Methods and Programs in Biomedicine, 82, 31-37 (2006); Sebaugh, J. L., Pharmaceutical Statistics, 10:128-134 (2011); Kelly, C. et al., Biometrics, 46(4):1071-1085 (1990); and Kahm, M. et al., Journal of Statistical Software, 33(7): (2010) (grofit: Fitting Biological Growth Curves with R, pages 1-21, available at http://www.jstatsoft.org/).Each compound was counterscreened to determine if it interfered with the AlphaScreen beads. Compounds were diluted as described in the preceding section, and the assay was performed by adding 12 μL of 10 nM biotin-miniPEG-His6 peptide in the above buffer and incubating for 20 min at rt prior to addition of the beads to 10 μg/mL each. The plates were then incubated for 1 h at rt in dark before being read on EnVison.
Measurement: IC50 = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 344.38, ALogP 2.73, HBA 7, HBD 1, PSA 77.23, QED 0.61
Compound (SMILES): Cc1c(C#N)cccc1[C@@H](C)Nc1nnc(C)c2cnc(N3CCOCC3)cc12
InChIKey: ILPWEAHQRAWJIU-OAHLLOKOSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Binding affinity to recombinant human N-terminal Avi tagged biotin-labelled SOS1 (564 to 1049 residues) by SPR assay
Measurement: Kd = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 388.48, ALogP 3.52, HBA 7, HBD 1, PSA 86.96, QED 0.73
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)CC[C@H](NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1)C(=O)O)C(=O)N[C@H](C(N)=O)C(C)C
InChIKey: DZZXXJLXJQWTGY-WFXMLNOXSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of human recombinant MMP-9 (Ala20 to Asp707 residues) using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 658.1, ALogP 1.14, HBA 7, HBD 6, PSA 213.86, QED 0.15
Compound (SMILES): O=c1[nH][nH]c(=O)c2cc(OCC3CCCC3)ccc12
InChIKey: KIMPACVVSQUMHL-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human PARP2 using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 260.29, ALogP 1.79, HBA 3, HBD 2, PSA 74.95, QED 0.88
Compound (SMILES): O=C(NO)c1ccc(CN(C2CC2)S(=O)(=O)c2cc(F)c(F)c(F)c2F)cc1
InChIKey: HYEWQOQZANKATO-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant full length human HDAC2 expressed in insect Sf9 cells by EMSA analysis
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 418.37, ALogP 2.72, HBA 4, HBD 2, PSA 86.71, QED 0.25
Compound (SMILES): N#Cc1ccc2c(c1)C[C@H](CO)N[C@@H]2c1cc(F)cc(Cl)c1
InChIKey: UOCQJHUNCIRIPU-NVXWUHKLSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Agonist activity at human TRPV1
Measurement: EC50 > 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 316.76, ALogP 2.95, HBA 3, HBD 2, PSA 56.05, QED 0.9
Compound (SMILES): Fc1c(-c2cccc3cccc(Cl)c23)ncc2c(N3CC4CCC(C3)N4)nc(OCC34CCCN3CCC4)nc12
InChIKey: FAKQXUSMRNQDHM-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: KRas G12D Binding Assay: Table 2: The ability of a compound to bind to KRAS G12D was measured using a TR-FRET displacement assay. Biotinylated GDP-loaded recombinant human KRAS G12D (corresponding to amino acids 1:169, produced at Array BioPharma) was incubated with a custom-made Cy5 labelled tracer, europium labelled streptavidin and compound (2% DMSO final) in buffer (50 mM HEPES [pH 7.5], 5mM MgCl2, 0.005% Tween-20 & 1 mM DTT). After a 60 minute incubation at 22° C., the reaction was measured using a PerkinElmer EnVision multimode plate reader via TR-FRET dual wavelength detection, and the percent of control (POC) calculated using a ratiometric emission factor. 100 POC is determined using no test compound and 0 POC is determined using a concentration of control compound that completely inhibits binding of the tracer to KRAS. The POC values were fit to a 4-parameter logistic curve and the IC50 value was determined as the concentration where the curve crosses 50 POC.
Measurement: IC50 = 840 nM (pChEMBL 6.079999923706055)
Descriptors: MW 559.09, ALogP 5.59, HBA 7, HBD 1, PSA 66.41, QED 0.34
Compound (SMILES): Cc1nc(N)sc1-c1ccc(N/C(N)=N/C(=O)NCC(C)CCCc2ccccc2)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: RANHYVDDWVKRSF-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]Nalpha-methylhistamine from human histamine H3 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing G-alphai2 and G-beta1gamma2 incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 450.61, ALogP 4.8, HBA 4, HBD 4, PSA 118.42, QED 0.29
Compound (SMILES): O=C(CCCCC/C=C\c1csc(Br)n1)NO
InChIKey: WLRUIAIHXAKVSH-XQRVVYSFSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of full length N-terminal GST/C-terminal his-tagged human recombinant HDAC4 (627 to 1084 residues) expressed in Sf9 insect cells
Measurement: IC50 = 7200 nM (pChEMBL 5.139999866485596)
Descriptors: MW 319.22, ALogP 3.37, HBA 4, HBD 2, PSA 62.22, QED 0.46
Compound (SMILES): Nc1ncc(-c2ccc(CN3CCC(N4CCOCC4)CC3)cc2Cl)nc1C(=O)NC12CCC(O)(CC1)CC2
InChIKey: RIGIHWPKCOSNDD-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of wild type ALK5 (unknown origin) assessed as enzymatic activity by microfluidic mobility shift assay
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 555.12, ALogP 3.24, HBA 8, HBD 3, PSA 116.84, QED 0.5
Compound (SMILES): Cc1nc(-c2cnc(NC(C)C)[nH]c2=O)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: UREZAFQRYNPCHA-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of CSF1R in CSF1-stimulated human THP-1 cells assessed as inhibition of CSF1R phosphorylation measured by ELISA assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 417.47, ALogP 3.55, HBA 8, HBD 2, PSA 110.61, QED 0.49
Compound (SMILES): CN(C)S(=O)(=O)c1ccc(OCCNCC2COc3ccccc3O2)cc1.Cl
InChIKey: ZLVODBUBXKSGHQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant CA9 assessed as inhibition constant pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 392.48, ALogP 1.75, HBA 6, HBD 1, PSA 77.1, QED 0.69
Compound (SMILES): C=CC(=O)N1CCC([C@@H]2CCNC3C(C(N)=O)C(c4ccc(Oc5ccccc5)cc4)=NN32)CC1
InChIKey: PZWSKESWDIFAFK-MUKMJDFVSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 473.58, ALogP 2.71, HBA 6, HBD 2, PSA 100.26, QED 0.63
Compound (SMILES): COc1ccc(Cc2nnc(Cc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)cc1
InChIKey: NNWKRTWKYDLFJC-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of [125I]-Tyr-SRIF 14 from SST5 receptor (unknown origin) expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 426.52, ALogP 4.31, HBA 5, HBD 2, PSA 84.41, QED 0.37
Compound (SMILES): Cn1cc(-c2ccc(N(C(=O)NCc3ccccc3)C3CCC(Nc4ccc(C#N)cn4)CC3)cc2)ccc1=O
InChIKey: HDJBGURZVALLMD-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14004
Assay: Inhibition of CDK13 (unknown origin)
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 532.65, ALogP 5.46, HBA 6, HBD 2, PSA 103.05, QED 0.33
Compound (SMILES): O=C1NC(Nc2ccc(N3CCCCC3)cc2)=N/C1=C\c1ccc2c(c1)OCO2
InChIKey: LZEXMGAAHJOEIB-PDGQHHTCSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of GST-fused human recombinant DYRK2 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 390.44, ALogP 3.34, HBA 6, HBD 2, PSA 75.19, QED 0.79
Compound (SMILES): COC1CCC(NC[C@@H](C(=O)N2CCN(c3ncnc4c3[C@H](C)CC(=O)N4)[C@H]3C[C@H]32)c2ccc(Cl)cc2)CC1
InChIKey: WZXPKDANYCNRFJ-HRZJXZCXSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes at 0.01 to 30 uM using mephenytoin as substrate in presence of NADPH by UPLC-MS/MS analysis
Measurement: IC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 553.11, ALogP 3.7, HBA 7, HBD 2, PSA 99.69, QED 0.54
Compound (SMILES): Cc1c(Br)cn(CCCc2cn(CCCCCn3c(C)c(Br)cc(C(=O)NC4CCCCCC4)c3=O)nn2)c(=O)c1NC(=O)C1CCCCCC1
InChIKey: XKLDAFLDOWXEFH-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]-CP55,940 from human CB1R expressed in CHO-K1 cell membranes assessed as inhibition constant incubated for 2 hrs by liquid scintillation spectrometry analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 831.69, ALogP 7.61, HBA 9, HBD 2, PSA 132.91, QED 0.13
Compound (SMILES): CNC(=O)N(c1ccc(S(=O)(=O)Nc2ncccn2)cn1)c1cc(F)c(-c2ccc(F)c(OC(F)(F)F)c2)cc1OC
InChIKey: GOQUVLJOFUKMGN-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human Nav1.7 by PatchXpress assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 610.52, ALogP 5, HBA 8, HBD 2, PSA 135.64, QED 0.27
Compound (SMILES): CC(=O)Nc1ccc(Nc2ncnc(N[C@@H](Cc3ccccc3)C(=O)OC(C)(C)C)n2)cc1
InChIKey: KJCRKFYABCQISR-FQEVSTJZSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate preincubated for 10 mins followed by NADPH addition and measured after 10 mins by LC/MS/MS analysis
Measurement: IC50 = 17700 nM (pChEMBL 4.75)
Descriptors: MW 448.53, ALogP 3.94, HBA 8, HBD 3, PSA 118.13, QED 0.44
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@@H]1C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@H](Cc2ccccc2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@H](C(N)=O)CSCc2cccc(c2)CSC1(C)C
InChIKey: GUWAZMLXUQIQKT-SIXPOYHZSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Agonist activity at human MC3R expressed in HEK293 cells assessed as maximal intracellular cAMP accumulation by fluorescence based analysis
Measurement: EC50 = 9.4 nM (pChEMBL 8.029999732971191)
Descriptors: MW 1135.43
Compound (SMILES): COc1cc2c(cc1OCCN1CCCCC1)C(=O)C(Cc1cccnc1)C2
InChIKey: OUWASZTUNZDMFL-UHFFFAOYSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13370
Assay: Inhibition of PDE3B (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 380.49, ALogP 3.55, HBA 5, HBD 0, PSA 51.66, QED 0.74
Compound (SMILES): COc1cc(S(N)(=O)=O)ccc1OCCC(N)C1COc2ccccc2O1
InChIKey: KOIYEFLKONFTEX-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Inhibition of human recombinant CA5B assessed as inhibition constant pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 409.7 nM (pChEMBL 6.389999866485596)
Descriptors: MW 394.45, ALogP 1.28, HBA 7, HBD 2, PSA 123.1, QED 0.72
Compound (SMILES): CCn1c(CO)nn(-c2nc(O[C@@H](C)C(F)(F)F)c(C(=O)Nc3c(C)ccnc3Cl)cc2F)c1=O
InChIKey: XEDJGCIOZDHXOR-JTQLQIEISA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes incubated for 10 mins by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 518.86, ALogP 3.02, HBA 9, HBD 2, PSA 124.16, QED 0.36
Compound (SMILES): COc1ccc(C2(C(=O)N3CS(=O)(=O)C[C@@H]3C(=O)Nc3cccc4[nH]ncc34)CCCC2)cc1
InChIKey: VWZAAFMUYDNGED-OAQYLSRUSA-N
Target: Histone acetyltransferase KAT6B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WYB5
Assay: Inhibition of MYST4 (unknown origin) using biotinylated H4 (1 to 25)-GSGSK peptide as substrate incubated for 1 hr by AlphaLISA assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 482.56, ALogP 2.61, HBA 6, HBD 2, PSA 121.46, QED 0.58
Compound (SMILES): O=C1NC(NC2CCNCC2)=N/C1=C\c1ccc2c(c1)OCO2
InChIKey: QGGNWMQODZFHNG-GHXNOFRVSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of GST-fused human recombinant DYRK1B expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 314.35, ALogP 0.58, HBA 6, HBD 3, PSA 83.98, QED 0.7
Compound (SMILES): COc1ccc(Cc2nnc(Cc3c[nH]c4cc(F)ccc34)n2CCCc2c[nH]cn2)cc1
InChIKey: LYMDSJLOXOXMHN-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of [125I]-Tyr-SRIF 14 from SST5 receptor (unknown origin) expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 444.51, ALogP 4.44, HBA 5, HBD 2, PSA 84.41, QED 0.35
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(Cl)c(O[C@@H]3CO[C@H]4[C@@H]3OC[C@H]4OC)n2)ccc1N(C)CCN(C)C
InChIKey: MXXJXRACSRJBKS-OHUMZHCVSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human JAK2
Measurement: IC50 = 2028 nM (pChEMBL 5.690000057220459)
Descriptors: MW 533.03, ALogP 2.56, HBA 10, HBD 2, PSA 110.31, QED 0.42
Compound (SMILES): Fc1ccc2c(Cc3nnc(Cc4cccc(C(F)(F)F)c4)n3CCCc3c[nH]cn3)c[nH]c2c1
InChIKey: HRMZYZYVRKSGFD-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of [125I]-Tyr-SRIF 14 from SST5 receptor (unknown origin) expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki = 6526 nM (pChEMBL 5.179999828338623)
Descriptors: MW 482.49, ALogP 5.45, HBA 4, HBD 2, PSA 75.18, QED 0.29
Compound (SMILES): FC(F)(F)c1cccc(COC2CCN(Cc3cc4ccc(Cl)cc4[nH]3)CC2)c1
InChIKey: UAYVZHLRDFXTFC-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 208.93 nM (pChEMBL 6.679999828338623)
Descriptors: MW 422.88, ALogP 6.02, HBA 2, HBD 1, PSA 28.26, QED 0.54
Compound (SMILES): Cn1cc(NC(=O)c2cc(C(=O)c3c(Cl)ccc(Cl)c3F)c[nH]2)cn1
InChIKey: LIEUQFMVFKJKHX-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase DCLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: O15075
Assay: Binding affinity to wild-type human partial length DCLK1 (L270 to A662 residues) expressed in mammalian expression system by Kinomescan assay
Measurement: Kd = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 381.19, ALogP 3.68, HBA 4, HBD 2, PSA 79.78, QED 0.53
Compound (SMILES): N#Cc1ccc(S[C@H]2O[C@H](CO)[C@H](O)[C@H](n3cc(-c4cc(F)c(F)c(F)c4)nn3)[C@H]2O)cc1Cl
InChIKey: RXISTOYAZFSXTN-OBJCFNGXSA-N
Target: Galectin-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P17931
Assay: Binding affinity to recombinant human Galectin-3 expressed in Escherichia coli assessed as dissociation constant by fluorescence polarization
Measurement: Kd = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 512.9, ALogP 2.66, HBA 9, HBD 3, PSA 124.42, QED 0.45
Compound (SMILES): Cc1cc(N)c(S(N)(=O)=O)cc1C(=O)Nc1cc(F)c(F)c(F)c1
InChIKey: RLCJNRRDMJQHSR-UHFFFAOYSA-N
Target: Core antigen (SINGLE PROTEIN), Hepatitis B virus
UniProt: Q03732
Assay: Modulation of capsid assembly in HBV genotype C infected in human HepG2.2.15 cells assessed as inhibition of viral DNA replication
Measurement: EC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 359.33, ALogP 1.89, HBA 4, HBD 3, PSA 115.28, QED 0.57
Compound (SMILES): CCn1c(CO)nn(-c2nc(O[C@@H](C)C(F)(F)F)c(C(=O)Nc3c(C)cnc(OC)c3Cl)cc2F)c1=O
InChIKey: FJYNLQXYLQBCRQ-JTQLQIEISA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes incubated for 10 mins by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 548.88, ALogP 3.03, HBA 10, HBD 2, PSA 133.39, QED 0.41
Compound (SMILES): C=CC(=O)N1CCC(C(=O)O)(c2ccc(Cl)cc2)CC1
InChIKey: BBISGFJIKYHGHR-UHFFFAOYSA-N
Target: F-box/LRR-repeat protein 19 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6PCT2
Assay: Inhibition of GST-tagged human FBXL19 (31 to 86 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay
Measurement: IC50 = 31000 nM (pChEMBL 4.510000228881836)
Descriptors: MW 293.75, ALogP 2.47, HBA 2, HBD 1, PSA 57.61, QED 0.87
Compound (SMILES): COc1cc(OC)c(Cl)c(Nc2ncccc2-c2ncnc(Nc3cnn(C4CCN(C(C)C)CC4)c3)n2)c1Cl
InChIKey: QPGRMRIBWAFOOC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 V564F mutant (unknown origin) by radiometric kinase activity assay
Measurement: IC50 = 189.1 nM (pChEMBL 6.71999979019165)
Descriptors: MW 584.51, ALogP 5.99, HBA 11, HBD 2, PSA 115.14, QED 0.24
Compound (SMILES): Cc1nc(NC(=O)NC(=O)C(C)C)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: LDFPZTVJHCRSKV-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of N-terminal His-Glu-TEV-tagged MET (unknown origin) (1050 to 1360 residues) measured by spectrophotometric analysis
Measurement: IC50 > 3300 nM (pChEMBL 5.480999946594238)
Descriptors: MW 394.44, ALogP 3.28, HBA 7, HBD 2, PSA 111.03, QED 0.69
Compound (SMILES): O=C1NC(=O)/C(=C\c2ccc(OCC(=O)N3N=C(c4ccccc4)CC3c3ccc(Cl)c(Cl)c3)cc2)S1
InChIKey: JTPZHEMUSATIFE-WYMPLXKRSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 using Boc-Lys(acetyl)-AMC as substrate incubated for 30 mins by fluorescence assay
Measurement: IC50 = 39000 nM (pChEMBL 4.409999847412109)
Descriptors: MW 552.44, ALogP 6.07, HBA 6, HBD 1, PSA 88.07, QED 0.38
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)C/C=C(\F)[C@@H](N)Cc1ccc(O)cc1)C(N)=O
InChIKey: JRQWLWZTKLOPSQ-ICXILOJFSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human delta opioid receptor expressed in CHO cells co-expressing beta-arrestin2 assessed as beta-arrestin2 recruitment measured after 90 mins by PathHunter assay
Measurement: EC50 = 954.99 nM (pChEMBL 6.019999980926514)
Descriptors: MW 555.65, ALogP 1.37, HBA 6, HBD 6, PSA 176.64, QED 0.19
Compound (SMILES): CCCC[C@@H]1NC(=O)[C@@H]2CSCc3ccccc3CSC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@H](Cc3cnc[nH]3)NC(=O)CNC1=O)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c3ccccc13)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: FIPGSBWOMGALGM-WPTGWSDQSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Agonist activity at human MC5R expressed in HEK2936E cells assessed as cAMP production in presence of IBMX by time resolved fluorescence assay
Measurement: IC50 = 204.17 nM (pChEMBL 6.690000057220459)
Descriptors: MW 2159.55
Compound (SMILES): O=C(NO)c1ccc(/C=N/NC(=O)c2cc(N3CCOCC3)nc(-c3cccc(O)c3)n2)cc1
InChIKey: QIXCKSONTDMMTH-ZVHZXABRSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin)
Measurement: IC50 = 72.8 nM (pChEMBL 7.139999866485596)
Descriptors: MW 462.47, ALogP 1.57, HBA 9, HBD 4, PSA 149.27, QED 0.24
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](N)CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]2CSSC[C@H](NC(=O)[C@H](CCC(N)=O)NC2=O)C(=O)N2CCC[C@H]2C(=O)N2CCC[C@H]2C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)O
InChIKey: SZCLBSHELXLOEC-OXOGCWQMSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P33032
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC5R expressed in CHO cells by Topcount beta counter analysis
Measurement: Ki = 28.84 nM (pChEMBL 7.539999961853027)
Descriptors: MW 2969.59
Compound (SMILES): COc1cc(-c2cc3c(N[C@H]4CCN(C(=O)C5CCC5)C4)ncnc3s2)cnc1OC
InChIKey: XIPMIAQFOCCQEU-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Mus musculus
UniProt: P42337
Assay: Inhibition of PI3Kalpha in IGF-1 stimulated mouse C2C12 cells incubated for 10 mins by AlphaLISA assay
Measurement: IC50 = 20777.8 nM (pChEMBL 4.679999828338623)
Descriptors: MW 439.54, ALogP 3.58, HBA 8, HBD 1, PSA 89.47, QED 0.63
Compound (SMILES): c1cc(CNc2ncc(-c3ccncc3)c3nncn23)c2c(c1)OCC2
InChIKey: ADDFHWGEAOKELS-UHFFFAOYSA-N
Target: Polycomb protein EED (SINGLE PROTEIN), Homo sapiens
UniProt: O75530
Assay: EED LC-MS Assay: Representative compounds of the present disclosure were serially and separately diluted 3-fold in DMSO to obtain a total of eight or twelve concentrations. Then the test compounds at each concentration (120 nL of each) were transferred by Mosquito into a 384-well Perkin Elmer ProxiPlate 384 plus plates. Solutions (6 μL) of 24 nM the wild type PRC2 (wtPRC2) complex and 2 μM SAM in reaction buffer (20 mM Tris, pH 8.0, 0.1% BSA, 0.01% Triton, 0.5 mM DTT) were added to the wells that were then incubated with the test compound for 20 min. A 6 μL solution of 3 μM of the peptide substrate H3K27Me0 (histone H3[21-44]-biotin) in reaction buffer was added to initiate each reaction. The final components in the reaction solution include 12 nM wtPRC2 complex, 1 μM SAM, and 1.5 μM H3K27me0 peptide with varying concentration of the compounds. A positive control consisted of the enzyme, 1 μM SAM and 1.5 μM substrate in the absence of the test compound, and a negative control consisted of 1 μM SAM and 1.5 μM substrate only. Each reaction was incubated at rt for 120 min, then stopped by addition of 3 μL per of quench solution (2.5% TFA with 320 nM d4-SAH). The reaction mixture was centrifuged (Eppendorf centrifuge 5810, Rotor A-4-62) for 2 min at 2000 rpm and read on an API 4000 triple quadrupole mass spec with Turbulon Spray (Applied Biosystem) coupled with Prominence UFLC (Shimadzu). The levels of SAH production were then normalized based on the values coming from the positive and negative controls to give percent enzyme activities. The data were then fit to a dose response equation using the program Helios to get the IC50 values of the test compound.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 344.38, ALogP 2.73, HBA 7, HBD 1, PSA 77.23, QED 0.61
Compound (SMILES): Cc1c(C#N)cccc1[C@@H](C)Nc1nnc(C)c2cnc(N3CCOCC3)cc12
InChIKey: ILPWEAHQRAWJIU-OAHLLOKOSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibition of SOS1 in human NCI-H358 cells harboring KRAS G12C mutant assessed as reduction in ERK phosphorylation measured after 1 hr by HTRF assay
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 388.48, ALogP 3.52, HBA 7, HBD 1, PSA 86.96, QED 0.73
Compound (SMILES): CC(C)C[C@H](NC(=O)CNC(=O)CC[C@H](NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1)C(=O)O)C(=O)N[C@H](C(N)=O)C(C)C
InChIKey: DZZXXJLXJQWTGY-WFXMLNOXSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of human recombinant MMP-12 (Leu17 to Cys470 residues) using MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 658.1, ALogP 1.14, HBA 7, HBD 6, PSA 213.86, QED 0.15
Compound (SMILES): O=c1[nH][nH]c(=O)c2cc(OCC3CCCC3)ccc12
InChIKey: KIMPACVVSQUMHL-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of human N-terminal 6His-tagged TNKS2 (1030 to 1317 residues) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 260.29, ALogP 1.79, HBA 3, HBD 2, PSA 74.95, QED 0.88
Compound (SMILES): O=C(NO)c1ccc(CN(C2CC2)S(=O)(=O)c2cc(F)c(F)c(F)c2F)cc1
InChIKey: HYEWQOQZANKATO-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant full length human HDAC4 expressed in insect Sf9 cells by EMSA analysis
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 418.37, ALogP 2.72, HBA 4, HBD 2, PSA 86.71, QED 0.25
Compound (SMILES): N#Cc1ccc2c(c1)C[C@H](CO)N[C@@H]2c1cc(F)cc(Cl)c1
InChIKey: UOCQJHUNCIRIPU-NVXWUHKLSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Agonist activity at human TRPM8 expressed in HEK cells assessed as increase in intracellular calcium level measured for 5 mins by FLIPR assay
Measurement: EC50 > 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 316.76, ALogP 2.95, HBA 3, HBD 2, PSA 56.05, QED 0.9
Compound (SMILES): Cc1nc(N)sc1-c1ccc(N/C(N)=N/C(=O)NCC(C)CCCc2ccccc2)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: RANHYVDDWVKRSF-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]UR-PI294 from human histamine H3 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing G-alphai2 and G-beta1gamma2 incubated for 60 mins by scintillation counting analysis
Measurement: Ki = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 450.61, ALogP 4.8, HBA 4, HBD 4, PSA 118.42, QED 0.29
Compound (SMILES): Nc1ncc(-c2ccc(CN3CCC(N4CCOCC4)CC3)cc2Cl)nc1C(=O)NC12CCC(O)(CC1)CC2
InChIKey: RIGIHWPKCOSNDD-UHFFFAOYSA-N
Target: Bone morphogenetic protein receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: O00238
Assay: Inhibition of wild type ALK6 (unknown origin) assessed as enzymatic activity using chemiluminescent substrate by ADP-Glo assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 555.12, ALogP 3.24, HBA 8, HBD 3, PSA 116.84, QED 0.5
Compound (SMILES): C=CC(=O)N1CCC([C@@H]2CCNC3C(C(N)=O)C(c4ccc(Oc5ccccc5)cc4)=NN32)CC1
InChIKey: PZWSKESWDIFAFK-MUKMJDFVSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of ERBB2 (unknown origin)
Measurement: IC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 473.58, ALogP 2.71, HBA 6, HBD 2, PSA 100.26, QED 0.63
Compound (SMILES): COc1ccc(Cc2nnc(Cc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)cc1
InChIKey: NNWKRTWKYDLFJC-UHFFFAOYSA-N
Target: Somatostatin receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P32745
Assay: Activity Assays: Measurement of forskolin stimulated inhibition of cAMP was performed via time-resolved fluorescence resonance energy transfer (TR-FRET) LANCE assay (AD0262, PerkinElmer Life Science, Inc., Boston Mass.). Recombinant Chinese hamster ovary (CHO-K1) cells expressing human somatostatin SSTR4 cells (ES-524-CF, PerkinElmer Life Science, Inc., Boston Mass.) were thawed (37° C.), resuspended in 10 mL Hanks' balanced salt solution no phenol red (HBSS, Invitrogen, Carlsbad Calif.), and then centrifuged (150×g, 5 minutes). Cellular pellet resuspended in stimulation buffer containing HBSS 1×, HEPES 5 mM, Protease free BSA 0.1% (PerkinElmer), and 3-Isobutyl-1-methylxanthine 0.5 mM (pH 7.4) and seeded in 96-well plates at 4000 cells/well. LANCE cAMP assay was performed per manufacture instruction with assessment of respective compound, somatostatin-28 (Sigma-Aldrich Co., St. Louis, Mo.) as control agonist, against 5 μM forskolin, performed in triplicate across concentration curve. Fluorescence signal was measured at 20 hours (excitation 340 nm and emission 665 nm, 400-μs delay) via TR-FRET (FLUOSTAR Omega-F, BMG Labtech, Inc., Cary, N.C.). Data was calculated via GraphPad PRISM-5 software.
Measurement: EC50 = 7.27 nM (pChEMBL 8.140000343322754)
Descriptors: MW 426.52, ALogP 4.31, HBA 5, HBD 2, PSA 84.41, QED 0.37
Compound (SMILES): Cn1cc(-c2ccc(N(C(=O)NCc3ccccc3)C3CCC(Nc4ccc(C#N)cn4)CC3)cc2)ccc1=O
InChIKey: HDJBGURZVALLMD-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 532.65, ALogP 5.46, HBA 6, HBD 2, PSA 103.05, QED 0.33