lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N[C@@H](CC(=O)O)Cn1nnc(-c2ccc(Oc3ccc(Cl)cc3)cc2)n1
InChIKey: VSQILWJHLPJYGP-ZDUSSCGKSA-N
Target: Cytochrome P450 3A5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20815
Assay: Reversible inhibition of CYP3A5 in human liver microsomes using midazolam as substrate incubated for 10 mins in presence of NADPH by LC-MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 373.8, ALogP 2.59, HBA 7, HBD 2, PSA 116.15, QED 0.65
Compound (SMILES): CN(CCC=C1c2ccccc2CCc2ccccc21)C(CCN)C(=O)NCc1ccccc1Cl
InChIKey: JPAMFFFLVIJEBI-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 1230 nM (pChEMBL 5.909999847412109)
Descriptors: MW 488.08, ALogP 5.23, HBA 3, HBD 2, PSA 58.36, QED 0.43
Compound (SMILES): CC[C@H]1CN2CCc3c([nH]c4cccc(OC)c34)[C@@H]2C[C@@H]1/C(=C\OC)C(=O)OC
InChIKey: LELBFTMXCIIKKX-CYSPOEIOSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]5-CT from human recombinant 5-HT7A receptor expressed in HEK cells by radioligand completion assay
Measurement: Ki = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 398.5, ALogP 3.83, HBA 5, HBD 1, PSA 63.79, QED 0.47
Compound (SMILES): Cl.O=C(NO)c1ccc(CN2c3ccccc3Sc3ccccc32)nc1
InChIKey: PCGYBRQMPFDGRF-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human HDAC2 using fluorogenic substrate incubated for 1 hrs by fluorescence plate reader assay
Measurement: IC50 = 1962 nM (pChEMBL 5.710000038146973)
Descriptors: MW 349.42, ALogP 4, HBA 5, HBD 2, PSA 65.46, QED 0.55
Compound (SMILES): O=C(O)CCCO/N=C1C(=C2/C(=O)Nc3ccccc32)/Nc2ccccc2/1
InChIKey: FCWICHXUWNYHMX-LCLDVOFVSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombiant human HDAC6 using fluorogenic HDAC substrate 3 measured after 30 mins by fluorescence microplate reader assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 363.37, ALogP 3.06, HBA 5, HBD 3, PSA 100.02, QED 0.43
Compound (SMILES): Cc1ccncc1-c1ccc2nc(NC(=O)C3CC3(F)F)sc2c1
InChIKey: UDGIEQXDGLYLDV-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: c-KIT Kinase Assay: ADP-Glo assay kit was purchased from Promega. Magnesium chloride (MgCl2), Manganese(II) chloride (MnCl2), Bovine serum albumin (BSA) and dimethylsulfoxide (DMSO) were purchased from Sigma-Aldrich. Tris-HCl buffer was purchased from Biosesang. c-Kit kinase and Poly (4:1 Glu, Tyr) Peptide were purchased from Signalchem.c-Kit kinase activity was measured by Promega's ADP-Glo Assay. In this assay, Recombinant human c-Kit (100 ng) is incubated with 5 μL of compounds (0.5% DMSO), 5 μL of Poly (4:1 Glu, Tyr) (250 ng/μl) and 5 μL of ATP (250 μM) in buffer (40 mM Tris, 7.5; 20 mM MgCl2; 0.1 mg/ml BSA; 2 mM MnCl2; 50M DTT). The assay was started by incubating the reaction mixture in a 96-well plate at 30° C. for 2 hr. After the incubation, 25 μL ADP-Glo reagent was added and the reaction was incubated at 30° C. for 45 min to stop the reaction and degrade residual ATP. The ADP product was then converted to ATP by adding 50 μL per well of detection reagent. Luminescence was detected after 30 min room temperature incubation with the Molecular device I3X plate reader. The IC50 values were calculated from a series of percent inhibition values determined at a range of inhibitor concentration using software routines as implemented in the GraphPad Prism 7 software or SigmaPlot 13.0.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 345.37, ALogP 4.26, HBA 4, HBD 1, PSA 54.88, QED 0.77
Compound (SMILES): CC(Oc1cc(Cl)cc(Cl)c1)c1nc(N)nc(N2CCN(C)CC2)n1
InChIKey: QNJWSDSFSUZCCQ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated with compounds for 20 mins followed by substrate addition and measured after 5 mins by Ellman's method
Measurement: IC50 = 3950 nM (pChEMBL 5.400000095367432)
Descriptors: MW 383.28, ALogP 2.65, HBA 7, HBD 1, PSA 80.4, QED 0.87
Compound (SMILES): O=C(CCCCCCC(=O)Nc1ccc2c(c1)[C@@]13CCN4CC5=CCO[C@H]6CC(=O)N2[C@H]1[C@H]6[C@H]5C[C@H]43)Nc1ccc2c(c1)[C@@]13CCN4CC5=CCO[C@H]6CC(=O)N2[C@H]1[C@H]6[C@H]5C[C@H]43
InChIKey: FIDNROXWZXYOPU-LRMVCSOMSA-N
Target: Glycine receptor (alpha-1/beta) (PROTEIN COMPLEX), Homo sapiens
UniProt: P48167
Assay: Antagonist activity at human glycine receptor subunit alpha-1beta expressed in HEK293 cells assessed as reduction in glycine-induced currents by whole-cell patch-clamp assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 837.03, ALogP 5.42, HBA 8, HBD 2, PSA 123.76, QED 0.25
Compound (SMILES): COC(=O)c1cccc(COc2c(-c3ccc(OCCOCCOCCn4cc(CN(CCO)Cc5ccccc5)nn4)cc3)oc3ccccc3c2=O)c1
InChIKey: ITPZKJDGQFUXAL-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of mitoxantrone resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 817 nM (pChEMBL 6.090000152587891)
Descriptors: MW 748.83, ALogP 5.52, HBA 13, HBD 1, PSA 147.61, QED 0.07
Compound (SMILES): CO[C@H]1CC[C@H](c2nnc3cnc4ccc(-c5cncc(C(F)F)c5)cc4n32)CC1
InChIKey: JPOWZUHXAXNZNE-WJYNOGRTSA-N
Target: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of DNA-PK in human HT-144 cells assessed as reduction in gammaH2AX phosphorylation incubated for 30 mins by fluorescence assay
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 409.44, ALogP 4.95, HBA 6, HBD 0, PSA 65.2, QED 0.48
Compound (SMILES): CCOC(=O)c1cnc(CCc2c[nH]c3ccccc23)nc1NCCCNC(=S)NCCC(=O)O
InChIKey: QTVOPLNICFPHFV-UHFFFAOYSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human recombinant SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys(Su)-AMC as substrate incubated for 1 hr in presence of 50 uM NAD+ by fluorescence based analysis
Measurement: IC50 = 5040 nM (pChEMBL 5.300000190734863)
Descriptors: MW 498.61, ALogP 2.66, HBA 7, HBD 5, PSA 141.26, QED 0.14
Compound (SMILES): CS(=O)(=O)c1nccc(-c2c(-c3cccc(OCc4ccccc4)c3)nc3sccn23)n1
InChIKey: DQOWVAQFOQHAFL-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG incubated for 3 hrs by competitive fluorescence tracer binding based assay
Measurement: IC50 = 12410 nM (pChEMBL 4.909999847412109)
Descriptors: MW 462.56, ALogP 4.5, HBA 8, HBD 0, PSA 86.45, QED 0.35
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ncncc2C(=O)c2cc(C(O)c3cccc(Cl)c3)cs2)C[C@@H]1O
InChIKey: PLMYHNPIXAICML-MIYFUGHMSA-N
Target: SUMO-activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBE0
Assay: Inhibition of SAE in human HCT116 cells assessed as reduction in redistribution of SUMO2/3 proteins from nucleus to cytosol incubated for 4 hrs by immunofluorescence assay
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 539.04, ALogP 2.28, HBA 10, HBD 4, PSA 164.73, QED 0.3
Compound (SMILES): CCC(Oc1cc(Cl)ccc1Cl)c1nc(N)nc(N2CCN(C)CC2)n1
InChIKey: VHYWETKTNNZSJF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-Raclopride from human 5-HT1AR expressed in HEK293 cells by radioligand binding assay
Measurement: Ki = 4760 nM (pChEMBL 5.320000171661377)
Descriptors: MW 397.31, ALogP 3.04, HBA 7, HBD 1, PSA 80.4, QED 0.83
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3ccccc32)cc1
InChIKey: NQVDRCWYKLNRPA-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 282.34, ALogP 2.76, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): COc1ncc2cc1NS(=O)(=O)c1cccc(c1)C(=O)NCc1ccc(s1)-c1ncnc3c(C)c-2sc13
InChIKey: LPJAKJUVEMSSSX-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3K p110delta/p85alpha by HTRF assay
Measurement: Ki = 0.08 nM (pChEMBL 10.100000381469727)
Descriptors: MW 549.66, ALogP 4.84, HBA 9, HBD 2, PSA 123.17, QED 0.31
Compound (SMILES): COc1cccc(-c2n[nH]cc2N2CCCNCC2)c1
InChIKey: WUZZYGJHJAEWDD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P28222
Assay: Binding affinity to 5HT1B receptor (unknown origin)
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 272.35, ALogP 1.89, HBA 4, HBD 2, PSA 53.18, QED 0.9
Compound (SMILES): CCCCCNC(=O)/N=C(\N)NCCCc1sc(N)nc1C
InChIKey: ZRQMUCDHVVOENY-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Agonist activity at human histamine H2 receptor expressed in HEK293T cells co-expressing ELucC by beta arrestin2 recruitment assay
Measurement: EC50 = 177.83 nM (pChEMBL 6.75)
Descriptors: MW 326.47, ALogP 1.77, HBA 4, HBD 4, PSA 118.42, QED 0.33
Compound (SMILES): Cc1ccc2cccc(S(=O)(=O)N3CCN(c4nccc5sccc45)CC3)c2n1
InChIKey: KLZSXJJLMWSGOR-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of ABCG2 (unknown origin) expressed in MDCK2-BCRP cells assessed as reduction in pheophorbide A accumulation measured after 120 mins by flow cytometric analysis
Measurement: IC50 = 9070 nM (pChEMBL 5.039999961853027)
Descriptors: MW 424.55, ALogP 3.66, HBA 6, HBD 0, PSA 66.4, QED 0.5
Compound (SMILES): FC(F)c1cncc(-c2ccc3ncc4nnc(C5=CCCCCC5)n4c3c2)c1
InChIKey: GCHBEJBYMQHZEM-UHFFFAOYSA-N
Target: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of DNA-PK in human HT-144 cells assessed as reduction in gammaH2AX phosphorylation incubated for 30 mins by fluorescence assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 391.43, ALogP 5.62, HBA 5, HBD 0, PSA 55.97, QED 0.45
Compound (SMILES): Cl.NCc1ccc(NC(=O)c2cc3ccccc3cc2O)cc1
InChIKey: QQBHVGUCTQZKMZ-UHFFFAOYSA-N
Target: Kallikrein-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06870
Assay: Competitive inhibition of KLK1 (unknown origin) assessed as release of AMC fluorescent product using H-PFR-AMC as substrate incubated for 30 mins by microplate reader
Measurement: Ki = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 292.34, ALogP 3.26, HBA 3, HBD 3, PSA 75.35, QED 0.69
Compound (SMILES): CCNC(=O)[C@H]1O[C@@H](n2cnc3c(NCCCCc4ccccc4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: ZFCWTCGMLFOWCC-RQXXJAGISA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]ZM241385 from human adenosine A2A receptor expressed in HeLa cells by beta scintillation counting analysis
Measurement: IC50 = 26500 nM (pChEMBL 4.579999923706055)
Descriptors: MW 440.5, ALogP 1.02, HBA 9, HBD 4, PSA 134.42, QED 0.36
Compound (SMILES): Cc1noc(-c2cc(-c3cc(S(=O)(=O)NCC(C)(C)O)ccc3C)cnc2N)n1
InChIKey: HAWIAVPLXUYCRU-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using L-alpha-phosphatidylinositol as substrate incubated for 30 to 60 mins in presence of ATP by Kinase Glo luminescence kinase assay
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 417.49, ALogP 2.05, HBA 8, HBD 3, PSA 144.23, QED 0.55
Compound (SMILES): CC(C)(C)Nc1c(-c2cccc(-c3nc4cc(-c5noc(C(F)(F)F)n5)ccc4[nH]3)c2)nc2cnccn12
InChIKey: CBLVNPKXHYVYCY-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of N-terminal GST-tagged human HDAC7 (518 to end residues) expressed in baculovirus-infected Sf9 cells assessed as reduction in 7-amino-4-methylcoumarin release measured every 5 mins by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 518.5, ALogP 6.22, HBA 8, HBD 2, PSA 109.82, QED 0.29
Compound (SMILES): Cc1cc(C(=O)N2CCC(c3cn([C@H]4CC[C@H](O)CC4)c4nc(NCC5CCCCC5)ncc34)CC2)cc(C)n1
InChIKey: MLEGYBAUGFHNOW-MCZWQBSQSA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: Activity Assay: Activity Against Tyro3 Tyrosine Kinase.
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 544.74, ALogP 5.93, HBA 7, HBD 2, PSA 96.17, QED 0.4
Compound (SMILES): COc1cc(-c2noc(COc3cc(C)nc4cccc(C)c34)n2)cc(OC)c1OC
InChIKey: NAPXQVUQYOKUGS-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of ABCG2 (unknown origin) expressed in MDCK2-BCRP cells assessed as reduction in pheophorbide A accumulation measured after 120 mins by flow cytometric analysis
Measurement: IC50 = 1310 nM (pChEMBL 5.880000114440918)
Descriptors: MW 421.45, ALogP 4.51, HBA 8, HBD 0, PSA 88.73, QED 0.43
Compound (SMILES): CCCC[C@H](NC(=O)[C@H](C)c1c(C)[nH]c2ccc(O)cc12)c1ncc(-c2cc3ccccc3nc2OC)[nH]1
InChIKey: CZYALTGXIQQGCT-NSYGIPOTSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Inhibition of human 5HT2B receptor
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 511.63, ALogP 6.28, HBA 5, HBD 4, PSA 115.92, QED 0.19
Compound (SMILES): Fc1ccc2c(C3CCN(CCCOc4ccc(CCN5CCCCC5)cc4)CC3)noc2c1
InChIKey: WAIZFEIVFOBJJX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Binding affinity to 5-HT6 receptor (unknown origin)
Measurement: Ki = 149.2 nM (pChEMBL 6.829999923706055)
Descriptors: MW 465.61, ALogP 5.64, HBA 5, HBD 0, PSA 41.74, QED 0.38
Compound (SMILES): CC[C@@H](NC(=O)c1ccc(Cl)cc1)[C@H]1[C@@H]2C[C@@H](n3cnc4cc(F)c(F)cc43)C[C@@H]21
InChIKey: PJRNKUWABSYXJP-PZJWQNMWSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using sulfaphenazole as substrate incubated for 10 mins in presence of NADPH by LCMS/MS analysis
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 429.9, ALogP 5.37, HBA 3, HBD 1, PSA 46.92, QED 0.59
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(C3CCN(C(=O)c4ccc(N(C)C)cc4)CC3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: WTBRDNQZOOILBP-MZBJOSPHSA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: Activity Assay: Activity Against Tyro3 Tyrosine Kinase.
Measurement: IC50 = 275 nM (pChEMBL 6.559999942779541)
Descriptors: MW 532.73, ALogP 5.59, HBA 7, HBD 2, PSA 86.52, QED 0.39
Compound (SMILES): CC(F)(F)CN1Cc2cc(C(F)(F)F)ncc2C2=CN=C(NCc3c(F)ccc4c3CCO4)N3C=NC(C1=O)C23
InChIKey: TVSLZNVEFBHYOJ-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 19700 nM (pChEMBL 4.710000038146973)
Descriptors: MW 564.49, ALogP 3.75, HBA 7, HBD 1, PSA 82.42, QED 0.57
Compound (SMILES): CC(Oc1ccc(Cl)c(Cl)c1)c1nc(N)nc(N2CCN(C)CC2)n1
InChIKey: PZIGYQHVJAFLAI-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-raclopride from human D2L receptor expressed in HEK293 cells measured after 1 hr by microbeta counting method
Measurement: Ki = 754 nM (pChEMBL 6.119999885559082)
Descriptors: MW 383.28, ALogP 2.65, HBA 7, HBD 1, PSA 80.4, QED 0.87
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2nc(Cc3ccccc3)n[nH]2)COc2cccnc21
InChIKey: XUZICJHIIJCKQQ-ZDUSSCGKSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human RIPK1 by ADP-Glo kinase assay
Measurement: Ki = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 378.39, ALogP 0.94, HBA 6, HBD 2, PSA 113.1, QED 0.7
Compound (SMILES): CSc1ccccc1C1CC1CNCCCCOc1ccc2c(c1)NC(=O)CC2
InChIKey: VEFKQCVWZLAVCM-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T cells co-expressing GFP2-beta-arrestin2 assessed as beta-arrestin2 recruitment preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay
Measurement: EC50 = 35.48 nM (pChEMBL 7.449999809265137)
Descriptors: MW 410.58, ALogP 4.85, HBA 4, HBD 2, PSA 50.36, QED 0.43
Compound (SMILES): COCc1ccc(OC(F)(F)F)c(CNC(=O)Nc2c(-c3ccccc3)nc3c(C)nccn23)c1
InChIKey: KNZNJSNITSGMNY-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Binding affinity to human full length TRKA at active state expressed in rat PC-12 cells assessed as induction of kinase conformational change at 52 degree C by CETSA assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 485.47, ALogP 5.07, HBA 6, HBD 2, PSA 89.78, QED 0.38
Compound (SMILES): Cc1ccc(CNC(=O)C(CCN)N(C)CCC=C2c3ccccc3CCc3ccccc32)cc1
InChIKey: LTGIWDWJRRMWFN-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 2350 nM (pChEMBL 5.630000114440918)
Descriptors: MW 467.66, ALogP 4.88, HBA 3, HBD 2, PSA 58.36, QED 0.47
Compound (SMILES): C[C@H]1CC2(CCN(c3ccc(C(=O)N4CCC(CN5Cc6cc7c(cc6C5)C(=O)N(C5CCC(=O)NC5=O)C7=O)CC4)cc3)CC2)CN1c1ccc(C#N)c(Cl)c1
InChIKey: GAXWAKXJBZHVQF-ZVENJKCTSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate pretreated for 5 mins followed by substrate addition and measured after 20 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 788.35, ALogP 5.37, HBA 9, HBD 1, PSA 137.37, QED 0.33
Compound (SMILES): CCc1cc2cnc(CN3CCN(c4ccc(C(=O)NC)nc4F)CC3)cc2[nH]c1=O
InChIKey: XKSQRLIEJSXRFK-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2NL67
Assay: Fluorescence Anisotropy Binding Assay: PARP6: Recombinant full length GST tagged PARP6 protein was diluted to 160 nM with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl and incubated for four hours with an equivalent volume of 6 nM fluorescent probe diluted with 50 mM Tris pH 8, 0.001% Triton X100, 10 mM MgCl2, 150 mM NaCl. The final DMSO concentration of the probe was kept below 1% (v/v).
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 424.48, ALogP 1.7, HBA 6, HBD 2, PSA 94.22, QED 0.61
Compound (SMILES): CC(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: JFVISPBLQYTSHU-VZNYXHRGSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse melanocortin receptor 4 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay based Schild analysis
Measurement: Kd = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 841.76, ALogP 0.2, HBA 7, HBD 11, PSA 283.29, QED 0.03
Compound (SMILES): O=S1(=O)CC2(OCCO2)c2cc3nccc(Nc4ccc5scnc5c4)c3cc21
InChIKey: BGDMMVIAARSUKG-UHFFFAOYSA-N
Target: Activin receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: P36896
Assay: Inhibition of human ALK4 using ATP as substrate incubated for 60 mins by ADP-glo based luminescence assay
Measurement: IC50 = 3737 nM (pChEMBL 5.429999828338623)
Descriptors: MW 425.49, ALogP 3.58, HBA 8, HBD 1, PSA 90.41, QED 0.52
Compound (SMILES): CN(C)c1nccn2c(-c3cnn(C)c3)c(-c3ccc(F)cc3)nc12
InChIKey: KASWNWVAOVGTLI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase haspin (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TF76
Assay: Inhibition of recombinant human HASPIN (470 to 798 residues) expressed in bacterial expression system using ARTKQTARKSTGGKAPRKQLA as substrate in presence of ATP measured after 30 mins by ADP-Glo assay
Measurement: IC50 = 7350 nM (pChEMBL 5.130000114440918)
Descriptors: MW 336.37, ALogP 3, HBA 6, HBD 0, PSA 51.25, QED 0.58
Compound (SMILES): Nc1ccc(C(=O)CCCN2CCN(c3ccccn3)CC2)cc1
InChIKey: JPLZGZBACZPXMR-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from human dopamine D4 receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 575.44 nM (pChEMBL 6.239999771118164)
Descriptors: MW 324.43, ALogP 2.45, HBA 5, HBD 1, PSA 62.46, QED 0.65
Compound (SMILES): Cc1c(F)c(N)cc(C(=O)Nc2cc(-n3cc(C(=O)NCCCN4CCOCC4)nn3)ccc2N2CCN(C)CC2)c1Cl
InChIKey: MPTAUAHHFUFKAG-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase, H3 lysine-79 specific (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TEK3
Assay: Inhibition of DOT1L (unknown origin)-mediated H3K79 methylation using histone H3 and SAM as substrate incubated for 30 mins by AlphaScreen assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 614.13, ALogP 2.41, HBA 10, HBD 3, PSA 133.88, QED 0.25
Compound (SMILES): COc1ccc(C2CC(c3ccccc3C)=NN2c2ccc(C(=O)NCCO)cc2)cc1
InChIKey: IAANKOGQBDQYIA-UHFFFAOYSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q14432
Assay: Inhibition of recombinant GST-tagged PDE3A (669 to end residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using FAM-cAMP as substrate incubated for 1.5 hrs by IMAP-FP assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.52, ALogP 4.08, HBA 5, HBD 2, PSA 74.16, QED 0.59
Compound (SMILES): Cc1cc(C(=O)N2CCC(c3cn([C@H]4CC[C@H](O)CC4)c4nc(N[C@H]5CCc6ccccc65)ncc34)CC2)cc(C)n1
InChIKey: GAZFCMBOTHVCNP-HEWUYBSCSA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: Activity Assay: Activity Against Tyro3 Tyrosine Kinase.
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 564.73, ALogP 6.04, HBA 7, HBD 2, PSA 96.17, QED 0.31
Compound (SMILES): CC(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@H](CCCCN)C(N)=O
InChIKey: KJJYWTBWCJTCNW-BWFYGAPHSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse melanocortin receptor 4 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay based Schild analysis
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 843.77, ALogP 3.53, HBA 6, HBD 7, PSA 201.3, QED 0.05
Compound (SMILES): COc1cc2c(cc1OC)C(=O)C(CC1(F)CCN(Cc3ccccc3F)CC1)C2
InChIKey: DCZOKUPYRTZAFN-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 in human hepatocytes
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 415.48, ALogP 4.59, HBA 4, HBD 0, PSA 38.77, QED 0.69
Compound (SMILES): Cc1cc(F)ccc1-c1cc2cc(CCC(=O)O)ccc2[nH]1
InChIKey: NENQUZKBDKDCRF-UHFFFAOYSA-N
Target: Free fatty acid receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5NUL3
Assay: Agonist activity at FFAR4 (unknown origin)
Measurement: EC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 297.33, ALogP 4.3, HBA 1, HBD 2, PSA 53.09, QED 0.75
Compound (SMILES): O=C(O)C(=O)O.O=C1CCc2cc(OCCCN3CCCN(c4ccccn4)CC3)ccc2N1
InChIKey: YLEPKPGFWMXHHA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-Ketanserin from human 5-HT2A receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 1132 nM (pChEMBL 5.949999809265137)
Descriptors: MW 380.49, ALogP 2.95, HBA 5, HBD 1, PSA 57.7, QED 0.78
Compound (SMILES): C[C@H]1CN(C(=O)CC[C@@]2(C)NC(=O)NC2=O)CCN1c1ccc(Cl)c(Cl)c1
InChIKey: UJRBIZNZOPPPEC-BBATYDOGSA-N
Target: A disintegrin and metalloproteinase with thrombospondin motifs 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O75173
Assay: Inhibition of human recombinant ADAMTS-4 (AA1 to 520) assessed as cleavage of fluorescent substrate using as TBIS-1 substrate incubated for 180 mins by biochemical assay
Measurement: IC50 = 635 nM (pChEMBL 6.199999809265137)
Descriptors: MW 413.31, ALogP 2.41, HBA 4, HBD 2, PSA 81.75, QED 0.74
Compound (SMILES): Clc1ccccc1-c1n[nH]cc1N1CCNCC1
InChIKey: GOIXEVXDQZBSIL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Homo sapiens
UniProt: P28221
Assay: Binding affinity to 5HT1D receptor (unknown origin)
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 262.74, ALogP 2.14, HBA 3, HBD 2, PSA 43.95, QED 0.87
Compound (SMILES): N[C@@H](CC(=O)O)Cn1nnc(-c2ccc(Oc3ccc(Cl)cc3)cc2)n1
InChIKey: VSQILWJHLPJYGP-ZDUSSCGKSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Displacement of [3H]WIN35428 from recombinant human dopamine transporter by radioligand binding assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 373.8, ALogP 2.59, HBA 7, HBD 2, PSA 116.15, QED 0.65
Compound (SMILES): CN(CCC=C1c2ccccc2CCc2ccccc21)C(CCN)C(=O)NCc1ccccc1Cl
InChIKey: JPAMFFFLVIJEBI-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human recombinant BACE1 using Rh-EVNLDAEFK-quencher as substrate incubated for 60 mins by FRET assay
Measurement: IC50 = 5130 nM (pChEMBL 5.289999961853027)
Descriptors: MW 488.08, ALogP 5.23, HBA 3, HBD 2, PSA 58.36, QED 0.43
Compound (SMILES): CC[C@H]1CN2CCc3c([nH]c4cccc(OC)c34)[C@@H]2C[C@@H]1/C(=C\OC)C(=O)OC
InChIKey: LELBFTMXCIIKKX-CYSPOEIOSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DAPT from human recombinant 5-HT1A receptor expressed in HEK cells measured after 60 to 90 mins by radioligand completion assay relative to control
Measurement: Ki = 38.5 nM (pChEMBL 7.420000076293945)
Descriptors: MW 398.5, ALogP 3.83, HBA 5, HBD 1, PSA 63.79, QED 0.47
Compound (SMILES): Cl.O=C(NO)c1ccc(CN2c3ccccc3Sc3ccccc32)nc1
InChIKey: PCGYBRQMPFDGRF-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of human HDAC11 using fluorogenic substrate incubated for 1 hrs by fluorescence plate reader assay
Measurement: IC50 = 4304 nM (pChEMBL 5.369999885559082)
Descriptors: MW 349.42, ALogP 4, HBA 5, HBD 2, PSA 65.46, QED 0.55
Compound (SMILES): O=C(O)CCCO/N=C1C(=C2/C(=O)Nc3ccccc32)/Nc2ccccc2/1
InChIKey: FCWICHXUWNYHMX-LCLDVOFVSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of HDAC7 (unknown origin) measured after 30 mins by fluorescence microplate reader assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 363.37, ALogP 3.06, HBA 5, HBD 3, PSA 100.02, QED 0.43
Compound (SMILES): CC(=O)Nc1ccc(CCCCN2CCN(c3ccccn3)CC2)cc1
InChIKey: KQZXADGECOXBKU-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 incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 352.48, ALogP 3.18, HBA 4, HBD 1, PSA 48.47, QED 0.78
Compound (SMILES): Cc1ccncc1-c1ccc2nc(NC(=O)C3CC3(F)F)sc2c1
InChIKey: UDGIEQXDGLYLDV-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: PDGFRalpha Kinase Assay: ADP-Glo assay kit was purchased from Promega. Magnesium chloride (MgCl2), Bovine serum albumin (BSA) and dimethylsulfoxide (DMSO) were purchased from Sigma-Aldrich. Tris-HCl buffer was purchased from Biosesang. PDGFRα kinase and Poly (4:1 Glu, Tyr) Peptide were purchased from Signalchem.PDGFRα kinase activity was measured by Promega's ADP-Glo Assay. In this assay, Recombinant human PDGFRα (40 ng) is incubated with 5 μL of compounds (0.5% DMSO), 5 μL of Poly (4:1 Glu, Tyr) (0.5 μg/μl) and 5 μL of ATP (125 μM) in buffer (40 mM Tris, 7.5; 20 mM MgCl2; 0.1 mg/ml BSA; 50 μM DTT). The assay was started by incubating the reaction mixture in a 96-well plate at 30° C. for 1 hr. After the incubation, 25 μL ADP-Glo reagent was added and the reaction was incubated at room temperature for 45 min to stop the reaction and degrade residual ATP. The ADP product was then converted to ATP by adding 50 μL per well of detection reagent. Luminescence was detected after 30-min room temperature incubation with the Molecular device I3X plate reader. The IC50 values were calculated from a series of percent inhibition values determined at a range of inhibitor concentration using software routines as implemented in the GraphPad Prism 7 software or SigmaPlot 13.0.
Measurement: IC50 = 5760 nM (pChEMBL 5.239999771118164)
Descriptors: MW 345.37, ALogP 4.26, HBA 4, HBD 1, PSA 54.88, QED 0.77
Compound (SMILES): CC(Oc1cc(Cl)cc(Cl)c1)c1nc(N)nc(N2CCN(C)CC2)n1
InChIKey: QNJWSDSFSUZCCQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Binding affinity to human 5HT2A receptor expressed in CHO-K1 cells assessed as inhibition constant incubated for 1 hr radioligand binding assay
Measurement: Ki = 412 nM (pChEMBL 6.380000114440918)
Descriptors: MW 383.28, ALogP 2.65, HBA 7, HBD 1, PSA 80.4, QED 0.87
Compound (SMILES): COC(=O)c1cccc(COc2c(-c3ccc(OCCOCCOCCn4cc(CN(CCO)Cc5ccccc5)nn4)cc3)oc3ccccc3c2=O)c1
InChIKey: ITPZKJDGQFUXAL-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 (unknown origin) expressed in human 2008/MRP1 cells assessed as reversal of mitoxantrone resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 592 nM (pChEMBL 6.230000019073486)
Descriptors: MW 748.83, ALogP 5.52, HBA 13, HBD 1, PSA 147.61, QED 0.07
Compound (SMILES): CO[C@H]1CC[C@H](c2nnc3cnc4ccc(-c5cncc(C(F)F)c5)cc4n32)CC1
InChIKey: JPOWZUHXAXNZNE-WJYNOGRTSA-N
Target: Alpha-1-antitrypsin-related protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20848
Assay: Inhibition of ATR in human HT29 cells assessed as reduction in gammaH2AX phosphorylation incubated for 30 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 409.44, ALogP 4.95, HBA 6, HBD 0, PSA 65.2, QED 0.48
Compound (SMILES): CCOC(=O)c1cnc(CCc2c[nH]c3ccccc23)nc1NCCCNC(=S)NCCC(=O)O
InChIKey: QTVOPLNICFPHFV-UHFFFAOYSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human recombinant SIRT5 (34 to 269 residues) using 300 uM Ac-Leu-Gly-Ser-Lys(Su)-AMC as substrate incubated for 1 hr in presence of 400 uM NAD+ by fluorescence based analysis
Measurement: IC50 = 32220 nM (pChEMBL 4.489999771118164)
Descriptors: MW 498.61, ALogP 2.66, HBA 7, HBD 5, PSA 141.26, QED 0.14
Compound (SMILES): CS(=O)(=O)c1nccc(-c2c(-c3cccc(OCc4ccccc4)c3)nc3sccn23)n1
InChIKey: DQOWVAQFOQHAFL-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) using EOMCC as a substrate incubated for 20 mins by fluorescence based analysis
Measurement: IC50 > 90000 nM (pChEMBL 4.046000003814697)
Descriptors: MW 462.56, ALogP 4.5, HBA 8, HBD 0, PSA 86.45, QED 0.35
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ncncc2C(=O)c2cc(C(O)c3cccc(Cl)c3)cs2)C[C@@H]1O
InChIKey: PLMYHNPIXAICML-MIYFUGHMSA-N
Target: SUMO-activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBE0
Assay: Inhibition of SAE in human HCT116 cells assessed as redistribution of SUMO2/3 proteins from nucleus to cytosol preincubated for 2 hrs followed by compound washout and measured immediately by immunofluorescence assay
Measurement: IC50 = 1210 nM (pChEMBL 5.920000076293945)
Descriptors: MW 539.04, ALogP 2.28, HBA 10, HBD 4, PSA 164.73, QED 0.3
Compound (SMILES): CCC(Oc1cc(Cl)ccc1Cl)c1nc(N)nc(N2CCN(C)CC2)n1
InChIKey: VHYWETKTNNZSJF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-Raclopride from human 5-HT2AR expressed in HEK293 cells by radioligand binding assay
Measurement: Ki = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 397.31, ALogP 3.04, HBA 7, HBD 1, PSA 80.4, QED 0.83
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCNC(=N)NC(=O)NCCCN)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: TUUPHEADJNWDNN-JPRYDEJLSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [3H]propionyl-pNPY from human neuropeptide Y Y5 receptor in human HEC-1B cells measured after 90 mins by scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 1125.3
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3ccccc32)cc1
InChIKey: NQVDRCWYKLNRPA-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 = 11100 nM (pChEMBL 4.960000038146973)
Descriptors: MW 282.34, ALogP 2.76, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): COc1ncc2cc1NS(=O)(=O)c1cccc(c1)C(=O)NCc1ccc(s1)-c1ncnc3c(C)c-2sc13
InChIKey: LPJAKJUVEMSSSX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of human PI3Kgamma by HTRF assay
Measurement: Ki = 0.44 nM (pChEMBL 9.359999656677246)
Descriptors: MW 549.66, ALogP 4.84, HBA 9, HBD 2, PSA 123.17, QED 0.31
Compound (SMILES): COc1cccc(-c2n[nH]cc2N2CCCNCC2)c1
InChIKey: WUZZYGJHJAEWDD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Homo sapiens
UniProt: P28221
Assay: Binding affinity to 5HT1D receptor (unknown origin)
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 272.35, ALogP 1.89, HBA 4, HBD 2, PSA 53.18, QED 0.9
Compound (SMILES): CCCCCNC(=O)/N=C(\N)NCCCc1sc(N)nc1C
InChIKey: ZRQMUCDHVVOENY-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from human D2L receptor expressed in HEK293T cells co-expressing CRE-Luc incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 446.68 nM (pChEMBL 6.349999904632568)
Descriptors: MW 326.47, ALogP 1.77, HBA 4, HBD 4, PSA 118.42, QED 0.33
Compound (SMILES): FC(F)c1cncc(-c2ccc3ncc4nnc(C5=CCCCCC5)n4c3c2)c1
InChIKey: GCHBEJBYMQHZEM-UHFFFAOYSA-N
Target: Alpha-1-antitrypsin-related protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20848
Assay: Inhibition of ATR in human HT29 cells assessed as reduction in gammaH2AX phosphorylation incubated for 30 mins by fluorescence assay
Measurement: IC50 = 2890 nM (pChEMBL 5.539999961853027)
Descriptors: MW 391.43, ALogP 5.62, HBA 5, HBD 0, PSA 55.97, QED 0.45
Compound (SMILES): Cc1noc(-c2cc(-c3cc(S(=O)(=O)NCC(C)(C)O)ccc3C)cnc2N)n1
InChIKey: HAWIAVPLXUYCRU-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma in human U937 cells assessed as reduction in AKT phosphorylation preincubated for 30 mins followed by MIP1alpha stimulation for 3 mins by fluorescence analysis
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 417.49, ALogP 2.05, HBA 8, HBD 3, PSA 144.23, QED 0.55
Compound (SMILES): CC(C)(C)Nc1c(-c2cccc(-c3nc4cc(-c5noc(C(F)(F)F)n5)ccc4[nH]3)c2)nc2cnccn12
InChIKey: CBLVNPKXHYVYCY-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of C-terminal His-tagged human HDAC9 (604 to 1066 residues) expressed in baculovirus-infected Sf9 cells assessed as reduction in 7-amino-4-methylcoumarin release measured every 5 mins by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 518.5, ALogP 6.22, HBA 8, HBD 2, PSA 109.82, QED 0.29
Compound (SMILES): Fc1ccc2c(C3CCN(CCCOc4ccc(CCN5CCCCC5)cc4)CC3)noc2c1
InChIKey: WAIZFEIVFOBJJX-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Binding affinity to alpha1 adrenoceptor (unknown origin)
Measurement: Ki = 536.1 nM (pChEMBL 6.269999980926514)
Descriptors: MW 465.61, ALogP 5.64, HBA 5, HBD 0, PSA 41.74, QED 0.38
Compound (SMILES): CC[C@@H](NC(=O)c1ccc(Cl)cc1)[C@H]1[C@@H]2C[C@@H](n3cnc4cc(F)c(F)cc43)C[C@@H]21
InChIKey: PJRNKUWABSYXJP-PZJWQNMWSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of Tracer Red from human ERG measured after 4 hrs by fluorescence polarization assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 429.9, ALogP 5.37, HBA 3, HBD 1, PSA 46.92, QED 0.59
Compound (SMILES): CC(F)(F)CN1Cc2cc(C(F)(F)F)ncc2C2=CN=C(NCc3c(F)ccc4c3CCO4)N3C=NC(C1=O)C23
InChIKey: TVSLZNVEFBHYOJ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 564.49, ALogP 3.75, HBA 7, HBD 1, PSA 82.42, QED 0.57
Compound (SMILES): CN1C(=O)[C@@H](NC(=O)c2nc(Cc3ccccc3)n[nH]2)COc2cccnc21
InChIKey: XUZICJHIIJCKQQ-ZDUSSCGKSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of RIPK1-dependent necroptosis in human U-937 cells
Measurement: IC50 = 12.3 nM (pChEMBL 7.909999847412109)
Descriptors: MW 378.39, ALogP 0.94, HBA 6, HBD 2, PSA 113.1, QED 0.7
Compound (SMILES): Cc1ccc(CNC(=O)C(CCN)N(C)CCC=C2c3ccccc3CCc3ccccc32)cc1
InChIKey: LTGIWDWJRRMWFN-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human recombinant BACE1 using Rh-EVNLDAEFK-quencher as substrate incubated for 60 mins by FRET assay
Measurement: IC50 = 4030 nM (pChEMBL 5.389999866485596)
Descriptors: MW 467.66, ALogP 4.88, HBA 3, HBD 2, PSA 58.36, QED 0.47
Compound (SMILES): C[C@H]1CC2(CCN(c3ccc(C(=O)N4CCC(CN5Cc6cc7c(cc6C5)C(=O)N(C5CCC(=O)NC5=O)C7=O)CC4)cc3)CC2)CN1c1ccc(C#N)c(Cl)c1
InChIKey: GAXWAKXJBZHVQF-ZVENJKCTSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate pretreated for 5 mins followed by substrate addition and measured after 5 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 788.35, ALogP 5.37, HBA 9, HBD 1, PSA 137.37, QED 0.33
Compound (SMILES): CCc1cc2cnc(CN3CCN(c4ccc(C(=O)NC)nc4F)CC3)cc2[nH]c1=O
InChIKey: XKSQRLIEJSXRFK-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: hERG Electrophysiological Assay: Electrophysiological recordings (all performed at RT) from stably transfected CHO hKv11.1 cells were obtained using the Nanion Syncropatch 768PE. Test compounds, vehicle or positive controls were added with 6 compound plates each at a different concentration to allow cumulative dosing onto cells (10 mM, 3.167 mM, 1 mM, 0.3167 mM, 0.1 mM, 0.03167 mM). 600 Figure US11325906-20220510-P00001of compound is resuspended into 90 μl of reference buffer (in mM, NaCl 80, KCL 4, CaCl 5, MgCl 1, NMDG Cl 60, D-Glucose monohydrate 5, HEPES 10 (pH7.4 HCL, 298 mOsm) for a final compound concentration of 39.6 μM, 13.2 μM, 4.4 μM, 1.46 μM, 0.48 μM, 0.16 μM. For each Nanion Syncropatch 768PE run, the current amplitude in each cell in the presence of extracellular solution (in mM, NaCl 80, KCL 4, CaCl 5, MgCl 1, NMDG Cl 60, D-Glucose monohydrate 5, HEPES 10 (pH7.4 HCL, 298 mOsm) is measured with all liquid additions performed using the Syncropatch liquid handling system. Add 40 μL external solution (in mM, HBPS, CaCl2 2, MgCl2 1 (pH7.4, NaOH) to 384 well multihole medium resistance recording chip and perfuse internal buffer (in mM, KF 130, KCl 20, MgCl2 1, EGTA 10, HEPES 10, Escin 25 (all Sigma-Aldrich; pH 7.2-7.30 using 10 M KOH, 320 mOsm) to the underside of plate. Dispense 20 μL of cells at a density of 1e6 cells/ml maintained at 9° C. into each well of the chip followed by 20 μL of seal enhancer (in mM, NaCl 80, KCl 3, CaCl 10, HEPES 10, MgCl 1 (pH7.4 NaOH). Perform wash step leaving a residual volume of 40 μL. Dispense 40 μL of reference buffer to establish a stable baseline prior to the addition of test compounds, with a removal step of 40 μL after 3 min, repeat this step. Dispense 40 μL of compound concentration 1 (0.16 μM), real time recordings for 3 min exposure prior to removal of 40 μL. This step is repeated for 5 further subsequent compound plates to generate cumulative curve analysis. All data is leak subtracted, 2 pulses to −80 mV 100 ms with 100 ms delay. Outward K+ currents are then evoked by voltage step to +60 mV from a holding potential of −90 mV, Each pulse is delivered at a frequency of 2 Hz with a 15 s pulse interval.
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 424.48, ALogP 1.7, HBA 6, HBD 2, PSA 94.22, QED 0.61
Compound (SMILES): CC(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: JFVISPBLQYTSHU-VZNYXHRGSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse melanocortin receptor 4 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay based Schild analysis
Measurement: Ki = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 841.76, ALogP 0.2, HBA 7, HBD 11, PSA 283.29, QED 0.03
Compound (SMILES): O=S1(=O)CC2(OCCO2)c2cc3nccc(Nc4ccc5scnc5c4)c3cc21
InChIKey: BGDMMVIAARSUKG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF (unknown origin) in presence of ATP by Lanthascreen TR-FRET assay
Measurement: IC50 = 1362 nM (pChEMBL 5.869999885559082)
Descriptors: MW 425.49, ALogP 3.58, HBA 8, HBD 1, PSA 90.41, QED 0.52
Compound (SMILES): Nc1ccc(C(=O)CCCN2CCN(c3ccccn3)CC2)cc1
InChIKey: JPLZGZBACZPXMR-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 incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 324.43, ALogP 2.45, HBA 5, HBD 1, PSA 62.46, QED 0.65
Compound (SMILES): Cc1c(F)c(N)cc(C(=O)Nc2cc(-n3cc(C(=O)NCCCN4CCOCC4)nn3)ccc2N2CCN(C)CC2)c1Cl
InChIKey: MPTAUAHHFUFKAG-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 (unknown origin)-mediated H3K27 methylation using histone H3 and SAM as substrate incubated for 30 mins by AlphaScreen assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 614.13, ALogP 2.41, HBA 10, HBD 3, PSA 133.88, QED 0.25
Compound (SMILES): COc1ccc(C2CC(c3ccccc3C)=NN2c2ccc(C(=O)NCCO)cc2)cc1
InChIKey: IAANKOGQBDQYIA-UHFFFAOYSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q14432
Assay: Inhibition of recombinant GST-tagged PDE3A (669 to end residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using TAMRA-cGMP as substrate incubated for 1.5 hrs by IMAP-FP assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.52, ALogP 4.08, HBA 5, HBD 2, PSA 74.16, QED 0.59
Compound (SMILES): CC(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@H](CCCCN)C(N)=O
InChIKey: KJJYWTBWCJTCNW-BWFYGAPHSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Agonist activity at mouse MC4R expressed in HEK293 cells assessed as induction of cAMP level incubated for 2 hr by alphaScreen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 843.77, ALogP 3.53, HBA 6, HBD 7, PSA 201.3, QED 0.05
Compound (SMILES): COc1cc2c(cc1OC)C(=O)C(CC1(F)CCN(Cc3ccccc3F)CC1)C2
InChIKey: DCZOKUPYRTZAFN-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human hepatocytes
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 415.48, ALogP 4.59, HBA 4, HBD 0, PSA 38.77, QED 0.69
Compound (SMILES): O=C(O)C(=O)O.O=C1CCc2cc(OCCCN3CCCN(c4ccccn4)CC3)ccc2N1
InChIKey: YLEPKPGFWMXHHA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-Ketanserin from human 5-HT2A receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 1122.02 nM (pChEMBL 5.949999809265137)
Descriptors: MW 380.49, ALogP 2.95, HBA 5, HBD 1, PSA 57.7, QED 0.78
Compound (SMILES): C[C@H]1CN(C(=O)CC[C@@]2(C)NC(=O)NC2=O)CCN1c1ccc(Cl)c(Cl)c1
InChIKey: UJRBIZNZOPPPEC-BBATYDOGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 413.31, ALogP 2.41, HBA 4, HBD 2, PSA 81.75, QED 0.74
Compound (SMILES): Clc1ccccc1-c1n[nH]cc1N1CCNCC1
InChIKey: GOIXEVXDQZBSIL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1E (SINGLE PROTEIN), Homo sapiens
UniProt: P28566
Assay: Binding affinity to 5HT1E receptor (unknown origin)
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 262.74, ALogP 2.14, HBA 3, HBD 2, PSA 43.95, QED 0.87
Compound (SMILES): CC[C@H]1CN2CCc3c([nH]c4cccc(OC)c34)[C@@H]2C[C@@H]1/C(=C\OC)C(=O)OC
InChIKey: LELBFTMXCIIKKX-CYSPOEIOSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DAPT from human recombinant 5-HT1A receptor expressed in CHO cells measured after 60 to 90 mins by radioligand completion assay relative to control
Measurement: Ki = 95.5 nM (pChEMBL 7.019999980926514)
Descriptors: MW 398.5, ALogP 3.83, HBA 5, HBD 1, PSA 63.79, QED 0.47