lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(-c2cc3occ(CNC4CCNC4)c3cc2-c2ccc(C#N)cc2)cc1
InChIKey: LOVNJYFCBFUYEC-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of N-terminal FLAG-tagged human recombinant MAO-A expressed in baculovirus-infected Sf9 cells by flow cytometry
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 407.52, ALogP 5.4, HBA 4, HBD 2, PSA 60.99, QED 0.47
Compound (SMILES): COc1cc2c(NC3CCN(Cc4ccc(C(=O)NO)cc4)CC3)cc(-c3ccc(C)o3)nc2cc1OCCCN1CCCC1
InChIKey: BRSOLPMHTWMRJJ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length human N-terminal GST-tagged HDAC6 using fluorogenic acetylated peptide as substrate incubated for 30 mins by fluorescence plate reader assay
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 613.76, ALogP 5.87, HBA 9, HBD 3, PSA 112.33, QED 0.1
Compound (SMILES): O=C1c2cc(Cl)c(Cl)cc2CC1CCN1CCN(c2ccccn2)CC1
InChIKey: PKODMLACMGNJDC-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from human dopamine D2 receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 3090.3 nM (pChEMBL 5.510000228881836)
Descriptors: MW 390.31, ALogP 3.96, HBA 4, HBD 0, PSA 36.44, QED 0.79
Compound (SMILES): CC(C)(C)c1cc(-c2oc(CCC(=O)O)nc2-c2ccccc2)cc(C(C)(C)C)c1
InChIKey: XNQOHHNGUXKESF-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P28702
Assay: Agonist activity at human RXRbeta transfected in human HEK293T cells co-expressing pFR/pRL-Luc incubated for 14 to 16 hrs by hybrid reporter gene assay
Measurement: EC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 405.54, ALogP 6.62, HBA 3, HBD 1, PSA 63.33, QED 0.52
Compound (SMILES): O=S(=O)(c1ccccc1)n1ccc2c(OCCNCC3CCCCC3)cccc21
InChIKey: MBFYHWHICKMNAR-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using BTC as substrate preincubated with enzyme for 5 mins followed by substrate addition for 5 mins by Ellman's method
Measurement: IC50 = 89.9 nM (pChEMBL 7.050000190734863)
Descriptors: MW 412.56, ALogP 4.43, HBA 5, HBD 1, PSA 60.33, QED 0.56
Compound (SMILES): CC(=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NCC(=O)NC1CCN(CC(=O)N2c3ccccc3NC(=O)c3ccccc32)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: BXNMTJSTNGIVGO-CGUOMVHUSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 832.97, ALogP -1.37, HBA 11, HBD 12, PSA 321.95, QED 0.04
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCNC(=N)N)C(C)C)C(=O)N1Cc2ccc(O)cc2C[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)O
InChIKey: HCFQEEUXFTYOPJ-MUVJKTISSA-N
Target: Type-2 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P50052
Assay: Displacement of [125-I]-[Sar1, Ile8] from recombinant human AT2R transfected in human HEK293 cells incubated for 2 hrs by liquid scintillation counter analysis
Measurement: IC50 = 315.4 nM (pChEMBL 6.5)
Descriptors: MW 969.15, ALogP 1.14, HBA 11, HBD 11, PSA 322.7, QED 0.04
Compound (SMILES): Clc1cnc(CNc2ccc3cnsc3c2)s1
InChIKey: IFAKEEVLFSLZPW-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Agonist activity at human TRPV4 expressed in HEK cells assessed as increase in GSK1016790A-induced intracellular calcium level measured after 1 hr by FLIPR assay
Measurement: EC50 > 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 281.79, ALogP 4.02, HBA 5, HBD 1, PSA 37.81, QED 0.79
Compound (SMILES): c1ccc2c(-c3ccc4c(c3)nnn4CC3CCNC3)c[nH]c2c1
InChIKey: AKKJQCHKYMPZSR-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO2 expressed in mouse P815B cells assessed as kynurenine concentration formation using L-tryptophan as substrate incubated for 7 hrs by UPLC analysis
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 317.4, ALogP 3.19, HBA 4, HBD 2, PSA 58.53, QED 0.61
Compound (SMILES): Cc1ccc([C@@H](NC(=O)Cn2nnc3ccccc3c2=O)C(C)C)cc1
InChIKey: CFJYBXKIJZZNRP-IBGZPJMESA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Displacement of (S)-N-(1-(2-[3H]-4-methoxyphenyl)propan-2-yl)-2-(2,3-dimethyl-7-oxothieno[2,3-d]pyridazin-6(7H)-yl)acetamide from human GPR139 expressed in CHO-TRex membranes incubated for 20 mins by scintillation counting assay
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 350.42, ALogP 2.61, HBA 5, HBD 1, PSA 76.88, QED 0.77
Compound (SMILES): Cc1cc(NC(=O)[C@H](O)c2cc(F)cc(F)c2)ccc1-c1cncc(C(=O)NC(C)C)c1
InChIKey: RPSNLKRQONAZHZ-JOCHJYFZSA-N
Target: Eukaryotic translation initiation factor 2 subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P05198
Assay: Inhibition of eIF2alpha (unknown origin) assessed as eIF2alpha phosphorylation by TR-FRET assay
Measurement: IC50 = 181 nM (pChEMBL 6.739999771118164)
Descriptors: MW 439.46, ALogP 4.15, HBA 4, HBD 3, PSA 91.32, QED 0.54
Compound (SMILES): COc1cc2c(cc1O)CN(Cc1ccccc1CNC(=O)c1cccc(Cl)c1)CC2
InChIKey: DJIHVEIRASRGEQ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-methylspiperone from dopamine D3 receptor (unknown origin)
Measurement: Ki = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 436.94, ALogP 4.54, HBA 4, HBD 2, PSA 61.8, QED 0.6
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN3C(=O)Cc2ccc(OC(F)(F)F)cc2)nc1-c1cnn(C(C)C)c1
InChIKey: HPZFOGKSPCGFKI-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human TYK2 (875 to end residues) using GGMEDIYFEFMGG as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting based radiometry assay
Measurement: IC50 = 51.06 nM (pChEMBL 7.289999961853027)
Descriptors: MW 536.56, ALogP 6, HBA 7, HBD 1, PSA 85.17, QED 0.31
Compound (SMILES): CC(C)CNC(=O)/C=C/C(=O)NC12CC3CC(C)(CC(C)(C3)C1)C2
InChIKey: OUIPJZLMWJGINA-AATRIKPKSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Mus musculus
UniProt: P34914
Assay: Inhibition of mouse recombinant sEH using PHOME as substrate measured after 10 mins by fluorescent based assay
Measurement: IC50 = 21120.3 nM (pChEMBL 4.670000076293945)
Descriptors: MW 332.49, ALogP 3.18, HBA 2, HBD 2, PSA 58.2, QED 0.76
Compound (SMILES): O=C(N[C@H](Cc1ccccc1)C(=O)O)c1cc(F)cc2cc(-c3ccc(Cl)cc3)oc12
InChIKey: MIUAQLGAIXHIPR-HXUWFJFHSA-N
Target: Endoplasmic reticulum aminopeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P179
Assay: Inhibition of ERAP2 (unknown origin) using Arg-AMC as substrate
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 437.85, ALogP 5.32, HBA 3, HBD 2, PSA 79.54, QED 0.43
Compound (SMILES): O=C(N/C=C/C=C/c1ccc2c(c1)OCO2)Nc1ccccc1C(=O)O
InChIKey: HRFYBSGCABRAKM-OXWOXFIQSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 measured after 15 mins by stopped flow carbon dioxide anhydrase assay
Measurement: Ki = 79500 nM (pChEMBL 4.099999904632568)
Descriptors: MW 352.35, ALogP 3.46, HBA 4, HBD 3, PSA 96.89, QED 0.72
Compound (SMILES): Cn1ncc(C(=O)Nc2cncc(-c3cc(Cl)cc(Cl)c3)c2N2CCC(N)CC2)c1C(F)(F)F
InChIKey: PZYGPMIBLQNMOM-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO-K1 cells with holding potential -80 mV incubated for 5 mins by patch-clamp assay
Measurement: IC50 = 7300 nM (pChEMBL 5.139999866485596)
Descriptors: MW 513.35, ALogP 4.99, HBA 6, HBD 2, PSA 89.07, QED 0.51
Compound (SMILES): CN(CCC=C1c2ccccc2CCc2ccccc21)C(CCN)C(=O)NCc1ccccc1
InChIKey: GNTZZKMAQQSFOH-UHFFFAOYSA-N
Target: GABA transporter 2 (SINGLE PROTEIN), Mus musculus
UniProt: P31651
Assay: Inhibition of mouse GAT2 expressed in human HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 40 mins by LC-ESI-MS/MS analysis
Measurement: IC50 = 9549.93 nM (pChEMBL 5.019999980926514)
Descriptors: MW 453.63, ALogP 4.57, HBA 3, HBD 2, PSA 58.36, QED 0.5
Compound (SMILES): COc1ccc2[nH]cc(CCNC(=O)Cn3cc(CN4CC[C@@]56C=C[C@H](O)C[C@@H]5Oc5c(OC)ccc(c56)C4)nn3)c2c1
InChIKey: BONSTVLWAPBWEJ-LZZMJICFSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChe using butyrylthiocholine iodide as substrate incubated for 25 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 8845 nM (pChEMBL 5.050000190734863)
Descriptors: MW 584.68, ALogP 2.86, HBA 9, HBD 3, PSA 126.76, QED 0.26
Compound (SMILES): Cl.Nc1c2c(nc3c(Cl)cc(Cl)cc13)CCCC2
InChIKey: LGCMTNAYQLXBAX-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human plasmatic BuChE assessed as reduction in cholinesterase activity by Ellman's method
Measurement: IC50 = 14800 nM (pChEMBL 4.829999923706055)
Descriptors: MW 267.16, ALogP 4, HBA 2, HBD 1, PSA 38.91, QED 0.78
Compound (SMILES): CC(C)(C)OC(=O)N1CCC(CNCCOc2cccc3c2ccn3S(=O)(=O)c2ccccc2)CC1
InChIKey: WFNXOOWTLDRZSS-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using BTC as substrate preincubated with enzyme for 5 mins followed by substrate addition for 5 mins by Ellman's method
Measurement: IC50 = 4824 nM (pChEMBL 5.320000171661377)
Descriptors: MW 513.66, ALogP 4.49, HBA 7, HBD 1, PSA 89.87, QED 0.45
Compound (SMILES): COc1ccccc1CCC(C)NCC(O)c1ccc(O)c2[nH]c(=O)ccc12.Cl
InChIKey: RNSUXBLOIHCQGQ-UHFFFAOYSA-N
Target: Beta-2 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07550
Assay: Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation
Measurement: EC50 = 0.01479 nM (pChEMBL 10.829999923706055)
Descriptors: MW 382.46, ALogP 2.89, HBA 5, HBD 4, PSA 94.58, QED 0.48
Compound (SMILES): O=C(NCC1CCN(Cc2ccccc2F)CC1)c1n[nH]c2ccc(-c3cccnc3)cc12
InChIKey: XGLLPXIGVHKLST-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel recombinant AChE preincubated for 1 min in presence of DNTB followed by addition of acetylthiocholine iodide substrate and measured after 20 mins by Ellman's method
Measurement: IC50 = 718 nM (pChEMBL 6.139999866485596)
Descriptors: MW 443.53, ALogP 4.41, HBA 4, HBD 2, PSA 73.91, QED 0.46
Compound (SMILES): CC12CC3CC(C)(C1)CC(NC(=O)/C=C/C(=O)NC1CCCCC1)(C3)C2
InChIKey: IFJZSDGUGZINOT-CMDGGOBGSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Mus musculus
UniProt: P34914
Assay: Inhibition of mouse recombinant sEH using PHOME as substrate measured after 10 mins by fluorescent based assay
Measurement: IC50 = 5516.1 nM (pChEMBL 5.260000228881836)
Descriptors: MW 358.53, ALogP 3.86, HBA 2, HBD 2, PSA 58.2, QED 0.75
Compound (SMILES): O=C(CN(Cc1ccc(C(=O)NO)cc1)C(=O)c1cccc2ccccc12)NCc1ccccc1
InChIKey: CAQWEFXQNVGTIF-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of N-terminal GST-tagged full length human recombinant HDAC6 expressed in baculovirus infected Sf9 cells using ZMAL (Z-Lys(Ac)-AMC) fluorogenic substrate incubated for 90 mins by fluorescence based assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 467.53, ALogP 3.92, HBA 4, HBD 3, PSA 98.74, QED 0.27
Compound (SMILES): N#Cc1ccc(-n2cc(-c3n[nH]c4cc(Cl)c(N[C@@H]5CCNC5)cc34)cn2)cc1
InChIKey: JMVBNURHAWPOMV-OAHLLOKOSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Displacement of K5 tracer from Axl (unknown origin) expressed in human HEK293 cells cotransfected with NanoLuc measured after 2 hrs by NanoBRET assay
Measurement: IC50 = 880 nM (pChEMBL 6.059999942779541)
Descriptors: MW 403.88, ALogP 3.71, HBA 6, HBD 3, PSA 94.35, QED 0.48
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(C(F)(F)F)c(-c4c[nH]c5ccccc45)n3)C2)cc1
InChIKey: JVGFGDPGTVUOKR-MOVYNIQHSA-N
Target: Cyclin-dependent kinase 7/ cyclin H (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 591.64, ALogP 5.42, HBA 6, HBD 3, PSA 106.25, QED 0.24
Compound (SMILES): CCN(CCCCCCOc1ccc(C(=O)/C=C/c2ccc(N(C)C)cc2)c(O)c1)Cc1ccccc1OC
InChIKey: JXDNZESCVUXGPQ-LTGZKZEYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P37136
Assay: Inhibition of rat cortex homogenate acetylcholinesterase by Ellman's method
Measurement: IC50 = 560 nM (pChEMBL 6.25)
Descriptors: MW 530.71, ALogP 6.82, HBA 6, HBD 1, PSA 62.24, QED 0.12
Compound (SMILES): COc1ncc2cc1NS(=O)(=O)c1cccc(c1)C(=O)NCc1cccc(c1)-c1ncnc3ccc-2cc13
InChIKey: HNWJIBREVXYDFW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant human GST tagged mTOR (1360 to 2549 residues) expressed in baculovirus expression system measured by LanthaScreen assay
Measurement: IC50 = 30.5 nM (pChEMBL 7.519999980926514)
Descriptors: MW 523.57, ALogP 4.41, HBA 7, HBD 2, PSA 123.17, QED 0.33
Compound (SMILES): Clc1ccc(-c2n[nH]cc2N2CCCNCC2)cc1
InChIKey: GQPFOKFRIDVKLE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from 5HT7 receptor (unknown origin) transfected in HEK293 cells incubated for 1.5 hrs by liquid scintillation counting
Measurement: Ki = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 276.77, ALogP 2.53, HBA 3, HBD 2, PSA 43.95, QED 0.89
Compound (SMILES): CCC[C@H](C)Nc1ncc2c(C3CCN(C(=O)c4ccncn4)CC3)cn([C@H]3CC[C@H](O)CC3)c2n1
InChIKey: PHINIAPYUBKDAN-JBACZVJFSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin)
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 491.64, ALogP 4.32, HBA 8, HBD 2, PSA 109.06, QED 0.51
Compound (SMILES): CC[C@@H](NC(=O)c1ccc(Cl)cc1)[C@H]1CC[C@H](c2nccc(OC)n2)CC1
InChIKey: LCRCVPMVOWUYNR-IIDMSEBBSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P28776
Assay: Inhibition of IDO1 in IFNgamma-stimulated mouse M109 cells preincubated for 2 hrs followed by recombinant murine IFNgamma stimulation and measured after 18 hrs by fluorescence based microplate reader assay
Measurement: IC50 = 193 nM (pChEMBL 6.710000038146973)
Descriptors: MW 387.91, ALogP 4.62, HBA 4, HBD 1, PSA 64.11, QED 0.78
Compound (SMILES): COc1ccc2nc(OC)n(CCNC(C)=O)c2c1
InChIKey: OSKMTHQTYBZVLY-UHFFFAOYSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Displacement of 2-[1251]-iodomelatonin from human MT2 receptor expressed in CHO cells incubated for 120 mins by scintillation counting analysis
Measurement: Ki = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 263.3, ALogP 1.19, HBA 5, HBD 1, PSA 65.38, QED 0.88
Compound (SMILES): CCC(=O)N1CCN(Cc2nc3ccccc3n2Cc2cccc(C)c2)CC1
InChIKey: CGOFIQVXLFMZKA-UHFFFAOYSA-N
Target: Retinal dehydrogenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O94788
Assay: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometry
Measurement: IC50 = 2090 nM (pChEMBL 5.679999828338623)
Descriptors: MW 376.5, ALogP 3.45, HBA 4, HBD 0, PSA 41.37, QED 0.68
Compound (SMILES): CC#C[C@]1(c2cc(NC(=O)c3cnc(OCF)cn3)ccc2F)N=C(N)OCC12CC(F)(F)C2
InChIKey: UKEKFCISVPCTHV-JOCHJYFZSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 (unknown origin) using APP harboring Swedish Lys/Met mutant-derived peptide as substrate incubated for 2 hrs by FRET assay
Measurement: IC50 = 2570 nM (pChEMBL 5.590000152587891)
Descriptors: MW 477.42, ALogP 3.15, HBA 7, HBD 2, PSA 111.72, QED 0.51
Compound (SMILES): CNC(=O)c1cc(C(=O)N[C@H]2C[C@@H]2C)cc(Cc2cccc3[nH]ccc23)n1
InChIKey: NKWGFXURQXWUHE-SGTLLEGYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from 6His-Thr tagged BRD4 BD2/BD1 Y97A mutant (1 to 477 residue) (unknown origin) measured after 30 mins by TR-FRET assay
Measurement: IC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 362.43, ALogP 2.65, HBA 3, HBD 3, PSA 86.88, QED 0.65
Compound (SMILES): COc1ncc2cc1NS(=O)(=O)c1ccc(F)c(c1)C(=O)NCc1ccc(s1)-c1ncnc3cc-2sc13
InChIKey: IICNWQTVBNJGKW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR (unknown origin) by LanthaScreen assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 553.62, ALogP 4.67, HBA 9, HBD 2, PSA 123.17, QED 0.31
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@@H]1COCCCCCC(=O)N2CCC[C@@]2(C)C(=O)N1)C(=O)[C@@]1(C)CO1
InChIKey: BINSOLVECRQKPH-BYIOMEFUSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of human 20S proteasome LMP7 using Ac-ANW-AMC as fluorogenic substrate measured every minute for 1 hr by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 465.59, ALogP 1.33, HBA 6, HBD 2, PSA 117.34, QED 0.57
Compound (SMILES): COc1cc2nc(-c3ccc(C)o3)cc(NCC3CCN(c4ccc(C(=O)NO)cn4)CC3)c2cc1OC
InChIKey: QLRMAMBVXWCJDE-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length human N-terminal GST-tagged HDAC6 using fluorogenic acetylated peptide as substrate incubated for 30 mins by fluorescence plate reader assay
Measurement: IC50 = 465 nM (pChEMBL 6.329999923706055)
Descriptors: MW 517.59, ALogP 4.66, HBA 9, HBD 3, PSA 121.98, QED 0.23
Compound (SMILES): CNc1ccc2ccc(OC[C@H]3O[C@@H](n4cc(-c5ccn(C)n5)c5c(N)ncnc54)[C@H](O)[C@@H]3O)cc2n1
InChIKey: RVDZYKPXBFJYRB-PXOHRUDZSA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3-mediated m6A methylation in human MOLM-3 cells assessed as reduction in mRNA level measured after 24 hrs by LC-MS/MS analysis
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 502.54, ALogP 1.7, HBA 12, HBD 4, PSA 158.39, QED 0.27
Compound (SMILES): CC(C)(C)Nc1c(-c2ccc(-c3noc(C(F)(F)F)n3)cc2)nc2ccccn12
InChIKey: QCKNTQLUQMEQRQ-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of C-terminal 6XHis-tagged human recombinant full length HDAC2 (1 to 488 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 401.39, ALogP 5.28, HBA 6, HBD 1, PSA 68.25, QED 0.51
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(CC(=O)N3CCCc4ccc(CC(C)C)cc43)cc2)cc1
InChIKey: SHJOFZGRYDGUOZ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at APC-labelled RORgammat (unknown origin) assessed as inhibition of biotinylated SRC recruitment measured after 1 hr by dual FRET assay
Measurement: IC50 = 31.5 nM (pChEMBL 7.5)
Descriptors: MW 532.71, ALogP 5.38, HBA 4, HBD 1, PSA 83.55, QED 0.4
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN3C(=O)C2CC2)nc1-c1cnn(C(C)C)c1
InChIKey: CWGBVVJEMFFMQL-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human TYK2 (875 to end residues) using GGMEDIYFEFMGG as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting based radiometry assay
Measurement: IC50 = 3.76 nM (pChEMBL 8.430000305175781)
Descriptors: MW 402.5, ALogP 4.27, HBA 6, HBD 1, PSA 75.94, QED 0.69
Compound (SMILES): N#Cc1ccc(-c2ccc(C[C@@H](C#N)NC(=O)[C@@H]3C[C@H]4CCC[C@H]4N3)cc2)cc1
InChIKey: IXUTYJAXGFAXCL-ACESQOTJSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of cellular cathepsin C (unknown origin)
Measurement: IC50 = 79.07 nM (pChEMBL 7.099999904632568)
Descriptors: MW 384.48, ALogP 3.31, HBA 4, HBD 2, PSA 88.71, QED 0.83
Compound (SMILES): Cl.Nc1cccc2c(S(=O)(=O)NCc3ccccc3)cccc12
InChIKey: YFAJNNAOUUTCEC-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase NSD2 (SINGLE PROTEIN), Homo sapiens
UniProt: O96028
Assay: Inhibition of NSD2 E1009K mutant (unknown origin) using SAM as substrate preincubated for 10 mins followed by substrate addition measured after 4 hrs by AlphaLISA method
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 312.39, ALogP 2.9, HBA 3, HBD 2, PSA 72.19, QED 0.73
Compound (SMILES): Cl.Nc1c2c(nc3ccc(F)cc13)CCC2
InChIKey: DZNXXSDOPDKQFW-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human plasmatic BuChE assessed as reduction in cholinesterase activity by Ellman's method
Measurement: IC50 = 1910 nM (pChEMBL 5.71999979019165)
Descriptors: MW 202.23, ALogP 2.44, HBA 2, HBD 1, PSA 38.91, QED 0.71
Compound (SMILES): NS(=O)(=O)c1ccc([Se]CC(O)CSc2ccc(Br)cc2)cc1
InChIKey: DJCQETJRQMDDRT-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human CA4 pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 481.3
Compound (SMILES): CCN1CCN(c2ccc(Nc3ncc(Cl)c(Nc4cccc(C(F)(F)F)c4)n3)nc2)CC1
InChIKey: ZIGDOWJPKOPVRE-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of human Cathepsin C in human U-937 cells using H-Gly-Phe-AFC as substrate pretreated for 60 mins followed by substrate addition incubated for 60 mins
Measurement: IC50 = 41.3 nM (pChEMBL 7.380000114440918)
Descriptors: MW 477.92, ALogP 5.17, HBA 7, HBD 2, PSA 69.21, QED 0.51
Compound (SMILES): O=C(O)CCc1nc(-c2ccccc2)c(-c2ccc(Cl)c(Cl)c2)o1
InChIKey: ZYKWXXMRTHWWKC-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P48443
Assay: Agonist activity at human RXRgamma transfected in human HEK293T cells co-expressing pFR/pRL-Luc incubated for 14 to 16 hrs by hybrid reporter gene assay
Measurement: EC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 362.21, ALogP 5.33, HBA 3, HBD 1, PSA 63.33, QED 0.67
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@@H]1CCC(=O)NCC(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: QLVBPSCWUQIUTJ-JTXVVRDHSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK299 from human neuropeptide Y Y1 receptor in human SK-N-MC cells measured after 90 mins by scintillation counting analysis
Measurement: Ki > 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 930.09, ALogP -4.93, HBA 12, HBD 18, PSA 452.72, QED 0.03
Compound (SMILES): O=C(Nc1ccc(Oc2ccnc3[nH]ccc23)cc1)Nc1cccc(C(F)(F)F)c1
InChIKey: MHIHRICEWVAMHY-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of p38alpha (unknown origin)
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 412.37, ALogP 6.02, HBA 3, HBD 3, PSA 79.04, QED 0.38
Compound (SMILES): Cc1cc(-c2c(C)nn(C)c2C)ccc1-c1nnc(N(C)Cc2ccc3ncc(-c4cnn(C)c4)n3c2)o1
InChIKey: UYUHIXSXWHTNEO-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLAG-tagged FLT3 (unknown origin) transfected in Cos-7 cells assessed as phosphorylation level incubated for 1 hr by ELISA
Measurement: IC50 = 12589.25 nM (pChEMBL 4.900000095367432)
Descriptors: MW 507.6, ALogP 4.75, HBA 10, HBD 0, PSA 95.1, QED 0.32
Compound (SMILES): O=C(O)c1cccc(COc2ccc(Cl)cc2Cl)c1F
InChIKey: WLYBGBUFHMNRTJ-UHFFFAOYSA-N
Target: Mas-related G-protein coupled receptor member X4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA9
Assay: Antagonist activity at human MRGPRX4 expressed in HEK cells incubated in dark for 1 hr at 37 degree C and then incubated for 30 mins at room temperature in presence of 100 uM of conjugated bilirubin by HTRF assay
Measurement: IC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 315.13, ALogP 4.41, HBA 2, HBD 1, PSA 46.53, QED 0.91
Compound (SMILES): N[C@@H](CC(=O)O)Cn1nnc(-c2ccc(Oc3ncc(Cl)cc3F)cc2)n1
InChIKey: ZEGMEJVULDALSH-NSHDSACASA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from recombinant human ERG stably expressed in HEK293 cell membranes measured after 90 mins by microbeta liquid scintillation counting method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 392.78, ALogP 2.12, HBA 8, HBD 2, PSA 129.04, QED 0.63
Compound (SMILES): COc1cccc(OC)c1-c1c(C2CC2)[nH]c(=O)c(-c2nnc(Cc3ccc(Cl)cc3)o2)c1O
InChIKey: OAWCDZDNMBSGLG-UHFFFAOYSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Intracellular cAMP Accumulation Assay: HEK293 cells stably expressing human APJ receptor were used to assess the activity of compounds. Cultured cells were detached and resuspended in the cAMP Homogeneous Time-Resolved Fluorescence (HTRF) assay buffer (Cisbio cat; #62AM4PEJ). The assay was performed in 384-well assay plates (Perkin-Elmer; cat #6008289) according to assay protocol provided by the manufacturer. Serial dilutions of a compound together with assay buffer containing 0.2 nM IBMX and 2 μM forskolin were added to each well containing 5,000 cells and incubated for 30 minutes at room temperature. Subsequently, cAMP D2 reagent was added in the lysis buffer followed by the EuK antibody (Cisbio; cat #62AM4PEJ) and incubated for 60 min. The fluorescence emission ratio was measured using fluorometer. The intracellular cAMP concentrations (compound-stimulated inhibition of forskolin-mediated cAMP production) were calculated by extrapolation from a standard curve using known cAMP concentrations. The EC50 values were obtained by fitting the data to a sigmoidal concentration-response curve with variable slope. The maximal achievable inhibition of forskolin-induced cAMP levels (Ymax) for each compound was expressed as relative percentage of inhibition attained using pyroglutamated apelin-13 ((Pyr1)apelin-13) peptide, which was set to 100%.The examples disclosed below were tested in the APJ in vitro assays described above and were found having human APJ cyclic AMP (hcAMP) activity. The EC50 value of each compound is presented at the end of the example description.
Measurement: EC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 479.92, ALogP 4.94, HBA 7, HBD 2, PSA 110.47, QED 0.39
Compound (SMILES): COc1ccnc(-c2nc3c(-c4ccc(CNC(=O)c5nc(C(C)(C)C)no5)c(F)c4)ccnc3[nH]2)c1
InChIKey: HGPFSNSANDROBL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human PBMC
Measurement: IC50 = 251 nM (pChEMBL 6.599999904632568)
Descriptors: MW 501.52, ALogP 4.45, HBA 8, HBD 2, PSA 131.71, QED 0.35
Compound (SMILES): C[C@@H]1CCN(c2nc(N3CCOCC3)cc(=O)[nH]2)[C@H]1Cc1ccccc1
InChIKey: OVFIHIWNXSZYOH-WBVHZDCISA-N
Target: Phosphatidylinositol 3-kinase catalytic subunit type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NEB9
Assay: Inhibition of full length recombinant GST-tagged human VPS34 expressed in baculovirus expression system using PI/PS as substrate incubated for 60 mins in presence of ATP at Km concentration by luminescence assay
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 354.45, ALogP 2.06, HBA 5, HBD 1, PSA 61.46, QED 0.91
Compound (SMILES): CN1CC=C(C2=Nc3cc(Cl)ccc3Nc3ccc(F)cc32)CC1
InChIKey: LMGVBWDCIXCGJJ-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Agonist activity at muscarinic M2 receptor (unknown origin) expressed in CHO cells
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 341.82, ALogP 4.92, HBA 3, HBD 1, PSA 27.63, QED 0.8
Compound (SMILES): O=C1NCc2c1cc(O[C@@H]1CCN(C(=O)C3CC3)C1)cc2-c1cc(O)cc(F)c1
InChIKey: ZDRCIAHNRHKJOD-MRXNPFEDSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) by HTRF assay
Measurement: IC50 = 381 nM (pChEMBL 6.420000076293945)
Descriptors: MW 396.42, ALogP 2.83, HBA 4, HBD 2, PSA 78.87, QED 0.83
Compound (SMILES): Cn1c(Cc2nn(CCCO)c(=O)c3ccccc23)nnc1SCCCCCCCC(=O)Nc1ccc(Cl)cc1Cl
InChIKey: FZMKBJNQMQEJQO-UHFFFAOYSA-N
Target: Interleukin-15 (SINGLE PROTEIN), Homo sapiens
UniProt: P40933
Assay: Inhibition of IL-15-induced STAT3 phosphorylation in human NK92 cells incubated for 30 mins followed by IL-15 stimulation and measured after 1 hr by alphascreen assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 617.6, ALogP 5.88, HBA 9, HBD 2, PSA 114.93, QED 0.13
Compound (SMILES): C[C@](O)(CN1CCOCC1)C(=O)Nc1ccc(C#N)c(C(F)(F)F)c1
InChIKey: IGJCUSRLDWMSLJ-HNNXBMFYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Human Androgen Receptor (hAR) Ligand Binding Domain (LBD) Affinity Assay: Methods: hAR-LBD (633-919) was cloned into pGex4t.1. Large scale GST-tagged AR-LBD was prepared and purified using a GST column. Recombinant AR-LBD was combined with [3H]mibolerone (PerkinElmer, Waltham, Mass.) in buffer A (10 mM Tris, pH 7.4, 1.5 mM disodium EDTA, 0.25 M sucrose, 10 mM sodium molybdate, 1 mM PMSF) to determine the equilibrium dissociation constant (Kd) of [3H]mibolerone. Protein was incubated with increasing concentrations of [3H]mibolerone with and without a high concentration of unlabeled mibolerone at 4° C. for 18 h in order to determine total and non-specific binding. Non-specific binding was then subtracted from total binding to determine specific binding and non-linear regression for the ligand binding curve with one site saturation was used to determine the Kd of mibolerone.Increasing concentrations of SARDs or DHT (range: 10−12 to 10−4 M) were incubated with [3H]mibolerone and AR-LBD using the conditions described above. Following incubation, the ligand bound AR-LBD complex was isolated using BiogelHT hydroxyapatite, washed and counted in a scintillation counter after adding scintillation cocktail.
Measurement: IC50 = 1019 nM (pChEMBL 5.989999771118164)
Descriptors: MW 357.33, ALogP 1.6, HBA 5, HBD 2, PSA 85.59, QED 0.85
Compound (SMILES): O=C(NCCO)N[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: XSLZOVDVKRRVRO-TUNNFDKTSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: General RORgamma Gal4 Reporter Assay: Inverse agonist activity of potential ligands to RORγ was measured by inhibition of luminescence in a Gal4-luciferase reporter assay in Jurkat cells.Jurkat cells stably over-expressing the RORγ receptor, Jurkat pEx/Gal/hRORγ CLBD/HYG pG5luc/blast, were plated at a concentration of 10,000 cells/well in a 384-well solid white cell culture plate (Perkin Elmer #6007899) in assay buffer RPMI 1640 (Gibco 11875-085 1L) containing 0.1% BSA, 100×HEPES (Gibco 15360-080), 100 mM sodium pyruvate (Gibco 11360-040), 50 mg/mL Hygromycin B (Invitrogen 10687-010) and 10 mg/mL blasticidin (Invitrogen R210-01). 100 nL of test compound in a 3-fold serial dilution, with final concentrations ranging from 40 μM to 0.67 nM, were added to the cells which were then incubated overnight.The following day, cells were lysed with 10 μL of Steady-Glo Luciferase Assay System (Promega Cat. No. EZ550), and analyzed immediately. IC50 values were determined. The IC50 value is defined as the concentration of test compound needed to reduce luciferase activity by 50% and is calculated using the four parameter logistic equation to fit the normalized data.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 600.53, ALogP 4.8, HBA 4, HBD 3, PSA 95.5, QED 0.33
Compound (SMILES): CCOc1nc2ccc3c(c2n1CCNC(C)=O)CCO3
InChIKey: ACDRXLLSQSDDRX-UHFFFAOYSA-N
Target: Melatonin receptor type 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P48039
Assay: Agonist activity at human MT1 receptor expressed in CHO cells assessed as increase in forskolin induced cAMP production incubated at 37 degreeC by HitHunter-cAMP assay
Measurement: EC50 = 0.037 nM (pChEMBL 10.430000305175781)
Descriptors: MW 289.34, ALogP 1.51, HBA 5, HBD 1, PSA 65.38, QED 0.91
Compound (SMILES): O=C(NO)c1ccc(CN2c3ccccc3Sc3ccc(C(=O)Nc4ccccn4)cc32)cc1
InChIKey: XIGDWHNBRJVSHI-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 using Boc Lys(TFA)-AMC as substrate preincubated for 5 mins followed by substrate addition and further incubated for 30 mins by fluorogenic assay
Measurement: IC50 = 730 nM (pChEMBL 6.139999866485596)
Descriptors: MW 468.54, ALogP 5.26, HBA 6, HBD 3, PSA 94.56, QED 0.27
Compound (SMILES): CCCCC1(c2cc(O)c3cc(Cc4ccccn4)c(=O)oc3c2)CCCCC1
InChIKey: CQLSDHCXDTZEHJ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in CHO-K1 cell membrane measured after 3 hrs by scintillation spectrometry
Measurement: Ki = 71.9 nM (pChEMBL 7.139999866485596)
Descriptors: MW 391.51, ALogP 5.88, HBA 4, HBD 1, PSA 63.33, QED 0.53
Compound (SMILES): COc1ncc2cc1NS(=O)(=O)c1cccc(c1)C(=O)NCc1cc(ccn1)-c1ccnc3ccc-2cc13
InChIKey: HGJSZYYEKFUQPI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant human GST tagged mTOR (1360 to 2549 residues) expressed in baculovirus expression system measured by LanthaScreen assay
Measurement: IC50 = 122 nM (pChEMBL 6.909999847412109)
Descriptors: MW 523.57, ALogP 4.41, HBA 7, HBD 2, PSA 123.17, QED 0.33
Compound (SMILES): CC(C)n1cc(C(=O)Nc2ccc(Oc3ncnc4c3CC(=O)N4)c(F)c2)c(=O)n(-c2ccc(F)cc2)c1=O
InChIKey: AYJMUFFYIOWRRM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Mus musculus
UniProt: Q00993
Assay: Inhibition of Axl in mouse BaF3 cells
Measurement: IC50 = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 534.48, ALogP 3.19, HBA 9, HBD 2, PSA 137.21, QED 0.39
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](CCCCN)C(N)=O
InChIKey: GQIQWHJELWBNLI-YXOGWZJSSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Agonist activity at mouse MC5R expressed in HEK293 cells assessed as induction of cAMP level at 100 uM incubated for 2 hr by alphaScreen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 813.74, ALogP 1.07, HBA 7, HBD 9, PSA 247.41, QED 0.03
Compound (SMILES): NS(=O)(=O)c1ccc(-n2cc(COc3ccnc(N4CCN(Cc5ccccc5)CC4)n3)nn2)cc1
InChIKey: MGKLBRXGMXYQKF-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 measured by stopped flow CO2 hydrase assay
Measurement: Ki = 39.1 nM (pChEMBL 7.409999847412109)
Descriptors: MW 506.59, ALogP 1.61, HBA 10, HBD 1, PSA 132.36, QED 0.38
Compound (SMILES): Cc1nc(C2CCOCC2)n2c1cnc1ccc(-c3cncc(C(F)F)c3)cc12
InChIKey: FUCGVOYZRSDCPC-UHFFFAOYSA-N
Target: Serine-protein kinase ATM (SINGLE PROTEIN), Homo sapiens
UniProt: Q13315
Assay: Inhibition of full-length N-terminal FLAG-tagged human ATM expressed in HEK293-6E cells using biotin-PEG2-SVEPPLSQETFSD as substrate preincubated for 15 mins followed by substrate addition and measured after 90 mins in presence of ATP by TR-FRET assay
Measurement: IC50 = 4020 nM (pChEMBL 5.400000095367432)
Descriptors: MW 394.43, ALogP 5.08, HBA 5, HBD 0, PSA 52.31, QED 0.49
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ncncc2C(=O)c2cc(C(O)c3cccc(Cl)c3)c(Cl)s2)C[C@@H]1O
InChIKey: SCHCQZKKFVETHG-LHYGDETCSA-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 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 573.48, ALogP 2.93, HBA 10, HBD 4, PSA 164.73, QED 0.28
Compound (SMILES): CC(=O)NCCC(C(=O)NCc1ccccc1Cl)N(C)CCC=C1c2ccccc2CCc2ccccc21
InChIKey: LEGOKNATDVFGNL-UHFFFAOYSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT3 expressed in human HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 40 mins by LC-ESI-MS/MS analysis
Measurement: IC50 = 17782.79 nM (pChEMBL 4.75)
Descriptors: MW 530.11, ALogP 5.4, HBA 3, HBD 2, PSA 61.44, QED 0.37
Compound (SMILES): O=C(O)c1ccc(-c2ccnc3ccccc23)cc1C1CCCC1
InChIKey: CPATWHLHNLJLTB-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N5S9
Assay: Inhibition of human CAMKK1 using CAMKKtide as substrate assessed as residual activity by [gamma-33P]-ATP assay relative to control
Measurement: IC50 = 239 nM (pChEMBL 6.619999885559082)
Descriptors: MW 317.39, ALogP 5.26, HBA 2, HBD 1, PSA 50.19, QED 0.72
Compound (SMILES): COc1ccc(F)cc1[C@@H]1C[C@H]1CNCCCCOc1ccc2ccc(=O)[nH]c2c1
InChIKey: KXRNXSYVAAEIGF-FXAWDEMLSA-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 Rluc8-tagged Galpahi1 assessed as Galphai1 dissociation preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay
Measurement: EC50 = 12.9 nM (pChEMBL 7.889999866485596)
Descriptors: MW 410.49, ALogP 4.23, HBA 4, HBD 2, PSA 63.35, QED 0.49
Compound (SMILES): CCC(NC(=O)c1ccc(Cl)cc1)[C@H]1[C@@H]2C[C@H](Oc3ccnc4ccccc34)C[C@@H]21
InChIKey: UAXPPQPDGOMVPD-LDFOQBSTSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 5 mins in presence of NADPH by LCMS/MS analysis
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 420.94, ALogP 5.5, HBA 3, HBD 1, PSA 51.22, QED 0.57
Compound (SMILES): Cc1cc(-c2c(C)n[nH]c2C)ccc1-c1nnc(N(C)Cc2ccc3nccn3c2)o1
InChIKey: RPUSHJJGPFEFGZ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) by LC-MS analysis
Measurement: IC50 = 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 413.49, ALogP 4.34, HBA 7, HBD 1, PSA 88.14, QED 0.46
Compound (SMILES): CCOC(=O)C(Nc1cccc(S(N)(=O)=O)c1)C(=O)c1ccccc1
InChIKey: WEICKRYAHQBIII-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 pre-incubated for 15 mins prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 58.6 nM (pChEMBL 7.230000019073486)
Descriptors: MW 362.41, ALogP 1.56, HBA 6, HBD 2, PSA 115.56, QED 0.44
Compound (SMILES): CC(=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC1CCN(CC(=O)N2c3ccccc3NC(=O)c3ccccc32)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: CDXYAIIHLIUNLC-CGUOMVHUSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]-NMS from human muscarinic M4 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 832.97, ALogP -1.37, HBA 11, HBD 12, PSA 321.95, QED 0.04
Compound (SMILES): CCCCC(C)(C)c1cc(OC)c2cc(Cc3ccccc3OC)c(=O)oc2c1
InChIKey: JOMUPPBQAZTNGK-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in CHO-K1 cell membrane measured after 3 hrs by scintillation spectrometry
Measurement: Ki = 229.09 nM (pChEMBL 6.639999866485596)
Descriptors: MW 394.51, ALogP 5.87, HBA 4, HBD 0, PSA 48.67, QED 0.45
Compound (SMILES): Cc1ncc(-c2cc(O[C@@H]3CCN(C(=O)C4CC4)C3)cc3c2CNC3=O)cc1NS(C)(=O)=O
InChIKey: FUDMGPWQXMKGKI-MRXNPFEDSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) by HTRF assay
Measurement: IC50 = 357 nM (pChEMBL 6.449999809265137)
Descriptors: MW 470.55, ALogP 2.06, HBA 6, HBD 2, PSA 117.7, QED 0.67
Compound (SMILES): CCC(NC(=O)c1ccc(Cl)cc1)[C@H]1[C@@H]2C[C@@H](n3cnc4cc(F)cc(F)c43)C[C@@H]21
InChIKey: AISFDGSJTOZJQL-PXFYCIBDSA-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 = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 429.9, ALogP 5.37, HBA 3, HBD 1, PSA 46.92, QED 0.59
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCN(C(=O)c3ccc[nH]3)CC2)cc1
InChIKey: PIQOCEGSWLPJKE-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human CA7 incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 7.6 nM (pChEMBL 8.119999885559082)
Descriptors: MW 362.41, ALogP 0.26, HBA 4, HBD 2, PSA 116.57, QED 0.81
Compound (SMILES): Cl.NCc1ccc(NC(=O)c2ccc3ccccc3c2O)cc1
InChIKey: HSLKONMQKCLMFU-UHFFFAOYSA-N
Target: Plasminogen (SINGLE PROTEIN), Homo sapiens
UniProt: P00747
Assay: Inhibition of plasmin (unknown origin) assessed as release of AMC fluorescent product using Boc-QAR-AMC as substrate incubated for 30 mins by microplate reader
Measurement: IC50 = 10200 nM (pChEMBL 4.989999771118164)
Descriptors: MW 292.34, ALogP 3.26, HBA 3, HBD 3, PSA 75.35, QED 0.69
Compound (SMILES): CC(=O)Nc1ccc(CN2CC(C(N)=O)Oc3ccccc32)cc1
InChIKey: KIQFINNMUMHBBQ-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NTG7
Assay: Inhibition of His6-tagged/TEV fused SIRT3 (unknown origin) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by NAD+ addition and measured after 30 mins by FLucK529Ac based luminescence assay
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 325.37, ALogP 1.9, HBA 4, HBD 2, PSA 84.66, QED 0.9
Compound (SMILES): COc1cc2c(NCC3CCN(c4ncc(C(=O)NO)cn4)CC3)cc(-c3ccc(C)o3)nc2cc1OCCCN1CCCC1
InChIKey: BZYQCFUKLXJLGU-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length human N-terminal GST-tagged HDAC6 using fluorogenic acetylated peptide as substrate incubated for 30 mins by fluorescence plate reader assay
Measurement: IC50 = 152 nM (pChEMBL 6.820000171661377)
Descriptors: MW 615.74, ALogP 4.91, HBA 11, HBD 3, PSA 138.11, QED 0.11
Compound (SMILES): O=C(Cn1c(=O)c(Cc2ccccc2)nc2ccccc21)NNC(=S)Nc1ccccc1
InChIKey: HSEJNGQSFXATBM-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of MAO-B (unknown origin) by fluorometric assay
Measurement: IC50 = 6.808 nM (pChEMBL 8.170000076293945)
Descriptors: MW 443.53, ALogP 3.01, HBA 5, HBD 3, PSA 88.05, QED 0.32
Compound (SMILES): Cc1cc(C(F)(F)F)ccc1OCc1cccc(C(=O)O)c1F
InChIKey: OYHLQUKEPNAYDV-UHFFFAOYSA-N
Target: Mas-related G-protein coupled receptor member X4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA9
Assay: Antagonist activity at human MRGPRX4 expressed in HEK cells incubated in dark for 1 hr at 37 degree C and then incubated for 30 mins at room temperature in presence of 100 uM of conjugated bilirubin by HTRF assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 328.26, ALogP 4.43, HBA 2, HBD 1, PSA 46.53, QED 0.84
Compound (SMILES): Cc1ccc(-c2n[nH]cc2N2CCNCC2)cc1
InChIKey: DRCWJTXHIZFXIO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Antagonist activity at human 5-HT7 receptor expressed in HEK293 cells assessed as reduction in cAMP accumulation incubated for 30 mins by microplate reader analysis
Measurement: IC50 = 1624 nM (pChEMBL 5.789999961853027)
Descriptors: MW 242.33, ALogP 1.79, HBA 3, HBD 2, PSA 43.95, QED 0.84
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)c(Cl)cc32)cc1
InChIKey: GXZOKLQVFRUCLC-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 = 2615 nM (pChEMBL 5.579999923706055)
Descriptors: MW 351.23, ALogP 4.07, HBA 3, HBD 2, PSA 52.57, QED 0.65
Compound (SMILES): CC(=O)NC(=O)[C@H](CCNC(=N)N)NC(=O)[C@@H]1CC(=O)NCCC[C@@H](C(=O)NCCN2CCN(CCCC3CCN(CC(=O)N4c5ccccc5NC(=O)c5ccccc54)CC3)CC2)N1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: VDXVZLQXPJDGSZ-QCEVHHGWSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]-NMS from human muscarinic M4 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 4.365 nM (pChEMBL 8.359999656677246)
Descriptors: MW 900.1, ALogP -0.21, HBA 12, HBD 9, PSA 266.53, QED 0.08
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N/N=C(/CS(=O)(=O)c2ccccc2)c2ccccc2)cc1
InChIKey: KZASMNJAPQGSMC-ATJXCDBQSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 by stopped-flow CO2 hydration assay
Measurement: Ki = 574.5 nM (pChEMBL 6.239999771118164)
Descriptors: MW 457.53, ALogP 1.94, HBA 6, HBD 2, PSA 135.76, QED 0.41