lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCCc1cn(CC(=O)Nc2ccc(Br)c(S(=O)(=O)N3CC[C@H](C)C3)c2)nn1
InChIKey: VOAIHKPTNKHSGO-ZDUSSCGKSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647-labeled ligand from BRD4 BD1 Y390A mutant (1 to 477 residue) (unknown origin) measured after 30 mins by TR-FRET assay
Measurement: IC50 = 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 470.39, ALogP 2.66, HBA 6, HBD 1, PSA 97.19, QED 0.67
Compound (SMILES): COc1cc2nnc3[nH]nc(C)c3c2cc1OC
InChIKey: NOAZBIGPIKIKDQ-UHFFFAOYSA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q14432
Assay: Inhibition of human GST-tagged PDE3A (484 to end residues) using cAMP as substrate measured after 60 mins
Measurement: IC50 = 1110 nM (pChEMBL 5.960000038146973)
Descriptors: MW 244.25, ALogP 1.83, HBA 5, HBD 1, PSA 72.92, QED 0.74
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1cccc(-c2cccc(OC(C)C)c2)c1
InChIKey: BCXSFLAKENGZCU-HSZRJFAPSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 469.58, ALogP 3.99, HBA 5, HBD 3, PSA 107.97, QED 0.13
Compound (SMILES): O=C(CCCCCN1C(=O)c2cccc3c(NCc4ccccc4)ccc(c23)C1=O)NO
InChIKey: PFADLOXEKLDOIQ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant C-terminal His-tagged human HDAC8 (1 to 377 residues) expressed in Baculovirus infected insect cells using RHK-K(Ac)-AMC as substrate by fluorimetric assay
Measurement: IC50 = 2460 nM (pChEMBL 5.610000133514404)
Descriptors: MW 431.49, ALogP 4.11, HBA 5, HBD 3, PSA 98.74, QED 0.2
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC)c2)o1)[C@@H](CC)N(C=O)OC(=O)c1cccc(-n2cccc2)c1
InChIKey: DGJRWSRUAFODPU-YZRKUJAWSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 801.85, ALogP 4.8, HBA 11, HBD 5, PSA 235.81, QED 0.03
Compound (SMILES): CCc1ccc(S(=O)(=O)Nc2ccc(-c3nc4ccccc4o3)cc2)cc1
InChIKey: YVYDRAJVYVADMM-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P54829
Assay: Inhibition of human PTPN5 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 31000 nM (pChEMBL 4.510000228881836)
Descriptors: MW 378.45, ALogP 4.86, HBA 4, HBD 1, PSA 72.2, QED 0.54
Compound (SMILES): O=c1oc2ccccc2c2nn(S(=O)(=O)c3ccccc3)cc12
InChIKey: AJNRXFUIGQGJKY-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using diC8-PI(4,5)P2 as substrate incubated for 3 hrs by fluorescence polarization assay
Measurement: IC50 = 56190 nM (pChEMBL 4.25)
Descriptors: MW 326.33, ALogP 2.38, HBA 6, HBD 0, PSA 82.17, QED 0.53
Compound (SMILES): C[C@@H]1CN(C(=O)Nc2ccc(-c3nc(N4CCOCC4)c4cnn(CCCCCCC(=O)NO)c4n3)cc2)CCO1
InChIKey: YPXRCUVTZDXVHY-HXUWFJFHSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant full length C-terminal His-tagged human HDAC8 expressed in baculovirus expression system using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by fluorescence assay
Measurement: IC50 = 1.28 nM (pChEMBL 8.890000343322754)
Descriptors: MW 566.66, ALogP 3.04, HBA 10, HBD 3, PSA 146.97, QED 0.19
Compound (SMILES): O=C(Nc1ccc2c(c1)B(O)OC2)c1cc(C(=O)Nc2ccc3c(c2)B(O)OC3)cc(C(=O)Nc2ccc3c(c2)B(O)OC3)c1
InChIKey: PZIRPPZPPHKRAJ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as reduction in CO2 hydration preincubated for 15 mins to 2 hrs by phenol red dye based stopped flow CO2 hydrase assay
Measurement: Ki = 8629 nM (pChEMBL 5.059999942779541)
Descriptors: MW 602.97
Compound (SMILES): COc1cccc2cc(-c3ccc([N+](=O)[O-])cc3)c(=O)oc12
InChIKey: UEQZBWZNEQUUQA-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine receptor A2B expressed in CHO cells assessed as suppression of NECA-induced decrease of cAMP accumulation by Glo-sensor cAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 297.27, ALogP 3.38, HBA 5, HBD 0, PSA 82.58, QED 0.42
Compound (SMILES): NS(=O)(=O)C[C@H]1COc2cc(F)ccc2N1C(=O)c1ccc2c(c1)NC(=O)CO2
InChIKey: FDWPXNLUFQNWMH-GFCCVEGCSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P22199
Assay: Antagonist activity at gal4-fused rat mineralocorticoid receptor LBD in expressed in human U2OS cells by luciferase reporter gene assay
Measurement: IC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 421.41, ALogP 0.85, HBA 6, HBD 2, PSA 128.03, QED 0.76
Compound (SMILES): CC(=O)N1N=C(c2ccc(Cl)cc2)CC1c1ccc(OS(N)(=O)=O)cc1
InChIKey: RRWCEXMTLFAJAV-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibitory constant incubated for 15 mins by phenol red dye based stopped flow assay
Measurement: Ki = 29.5 nM (pChEMBL 7.53000020980835)
Descriptors: MW 393.85, ALogP 2.62, HBA 5, HBD 1, PSA 102.06, QED 0.86
Compound (SMILES): Cc1ccc(S(=O)(=O)N2C(=O)NC3(CCCc4ccccc43)C2=O)cc1
InChIKey: LXXQXOMQCGHKBG-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P07943
Assay: Inhibition of ALR2 in rat lens assessed as reduction in sorbitol accumulation incubated for 3 hrs in presence of 28 mM glucose by gas chromatographic analysis relative to control
Measurement: IC50 = 1560 nM (pChEMBL 5.809999942779541)
Descriptors: MW 370.43, ALogP 2.47, HBA 4, HBD 1, PSA 83.55, QED 0.82
Compound (SMILES): CC(=O)N1N=C(c2ccc(OS(N)(=O)=O)cc2)CC1c1c(Cl)cccc1Cl
InChIKey: XDPKIQYCGBZKLX-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibitory constant incubated for 15 mins by phenol red dye based stopped flow assay
Measurement: Ki = 43.7 nM (pChEMBL 7.360000133514404)
Descriptors: MW 428.3, ALogP 3.27, HBA 5, HBD 1, PSA 102.06, QED 0.81
Compound (SMILES): COc1cccc(NC(=O)c2cncc(N3CC4CC(C3)N4)c2)c1
InChIKey: ZLVRFKCBPDMHFZ-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Agonist activity at human alpha4beta2 nAChR expressed in GH4C1 cells assessed as increase in inward channel current measured after 3 to 4 days at -70 mV holding potential by patch clamp assay
Measurement: EC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 324.38, ALogP 1.89, HBA 5, HBD 2, PSA 66.49, QED 0.9
Compound (SMILES): COc1cc2c(N[C@H](C)c3ccc(F)cc3)nc(C)nc2cn1
InChIKey: KPKUASJRSIECLJ-SNVBAGLBSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR phosphorylation at Y 1173 residues in human HeLa cells preincubated for 30 mins followed by EGF-stimulation and measured after 2 mins by ELISA
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 312.35, ALogP 3.65, HBA 5, HBD 1, PSA 59.93, QED 0.8
Compound (SMILES): Cc1cc(N)nc(CCc2cc(CC[C@H]3CCCN3C)cc(F)c2F)c1
InChIKey: DWIFPRVVASXUJK-GOSISDBHSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29476
Assay: Inhibition of rat neuronal NOS expressed in Escherichia coli using L-arginine as substrate in presence of human oxyhemoglobin after 6 mins by hemoglobin NO capture assay
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 359.46, ALogP 4.06, HBA 3, HBD 1, PSA 42.15, QED 0.85
Compound (SMILES): O=C(Nc1ccc2c(c1)C(=O)NS2(=O)=O)c1cccc(Cl)c1
InChIKey: WJSNUMIOITZHKE-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 preincubated for 15 mins by stopped flow CO2 hydration assay
Measurement: Ki = 38.7 nM (pChEMBL 7.409999847412109)
Descriptors: MW 336.76, ALogP 2.02, HBA 4, HBD 2, PSA 92.34, QED 0.88
Compound (SMILES): Cc1cccc(OCc2nc(N)nc(N3CCN(C)CC3)n2)c1
InChIKey: FGOIXPDJFSFBTI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-Ketanserin from human 5-HT2A expressed in CHO-K1 cells incubated for 1.5 hrs by radioligand binding assay
Measurement: Ki = 2274 nM (pChEMBL 5.639999866485596)
Descriptors: MW 314.39, ALogP 1.09, HBA 7, HBD 1, PSA 80.4, QED 0.9
Compound (SMILES): Cc1ccc([Te]Cc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: ARFHGTGKXRNEDW-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 388.95
Compound (SMILES): COc1cccc(N2CCN(CCCCCCN3C(=O)c4cccc5cccc(c45)C3=O)CC2)c1
InChIKey: KQYVDEWSKFDTLI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from recombinant human 5HT6 receptor expressed in HEK293 cells measured after 1 hr by microbeta counting method
Measurement: Ki = 347 nM (pChEMBL 6.460000038146973)
Descriptors: MW 471.6, ALogP 4.83, HBA 5, HBD 0, PSA 53.09, QED 0.33
Compound (SMILES): CO[C@]1(C(=O)N2CC[C@](c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3)(S(=O)(=O)c3ccc(F)cc3)C2)CC[C@H](C(=O)O)CC1
InChIKey: VOICMNBKPATLIE-AJHZIAPWSA-N
Target: Nuclear receptor ROR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92753
Assay: Inverse agonist activity at human Gal4-fused RORbeta LBD (200 to 559 residues) expressed in human Jurkat cells measured after 18 hrs by steady-glo luciferase reporter gene assay
Measurement: EC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 657.58, ALogP 5.68, HBA 5, HBD 1, PSA 100.98, QED 0.3
Compound (SMILES): CN(C)C(=O)N[C@H]1CC[C@H](CCN2CCc3cccc(F)c3C2)CC1
InChIKey: YKLLQSPNTXNQJT-JCNLHEQBSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at D2L receptor (unknown origin) expressed in human HTLA cells assessed as beta-arrestin2 recruitment after 20 to 22 hrs by brightglo-luciferase reporter gene assay
Measurement: EC50 = 60.26 nM (pChEMBL 7.21999979019165)
Descriptors: MW 347.48, ALogP 3.4, HBA 2, HBD 1, PSA 35.58, QED 0.91
Compound (SMILES): C[C@@H]1C[C@H](O)[C@@]2(C)C(C(=O)O)=CCC[C@@H]2[C@@]1(C)CCc1ccoc1.N
InChIKey: QENGBUDRUMRCDR-CGTWFDGSSA-N
Target: Endoplasmic reticulum aminopeptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NZ08
Assay: Inhibition of full length C-terminal His6-tagged ERAP1 (unknown origin)-mediated chicken ovalbumin antigenic epitope processing assessed as reduction in SIINFEKL generation using SGLEQLESIINFEKL as substrate measured after 30 mins by Rapidfire-MS analysis
Measurement: IC50 = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 332.44, ALogP 4.05, HBA 3, HBD 2, PSA 70.67, QED 0.87
Compound (SMILES): CCOC1Cc2ccccc2[C@]2(CC[C@@H](NCC3CCCCC3)CC2)O1
InChIKey: LKSVIRCJQQMHGO-FXCIWXGGSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from delta opioid receptor in rat membranes after 120 mins by scintillation counting analysis
Measurement: Ki = 185 nM (pChEMBL 6.730000019073486)
Descriptors: MW 357.54, ALogP 4.93, HBA 3, HBD 1, PSA 30.49, QED 0.81
Compound (SMILES): O=C(Nc1ccc2[nH]ccc2n1)c1ccc(F)c(F)c1
InChIKey: OVKUJIWKLRCCMQ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B expressed in baculovirus infected BTI-TN-5B1-4 insect cells using p-tyramine as substrate preincubated for 15 mins and measured after 45 mins by resorufin-based fluorescence assay
Measurement: IC50 = 46.1 nM (pChEMBL 7.340000152587891)
Descriptors: MW 273.24, ALogP 3.09, HBA 2, HBD 2, PSA 57.78, QED 0.75
Compound (SMILES): CCOc1cccc(-c2cccc(C(=O)NCNC(=O)[C@H](CC3CCCC3)CN(O)C=O)c2)c1
InChIKey: YBOKJFMPYGEQQO-HSZRJFAPSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 467.57, ALogP 3.6, HBA 5, HBD 3, PSA 107.97, QED 0.19
Compound (SMILES): COc1ccc(-c2oc3ccccc3c2C(=O)c2ccc(N(Cc3ccccc3)Cc3ccccc3)cc2)cc1
InChIKey: CGLYNQHJAXXHAK-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of 3[H]-CP55940 from human recombinant CB2 receptor expressed in HEK293 cell membranes measured after 90 mins by Cheng-Prusoff equation analysis
Measurement: Ki = 920 nM (pChEMBL 6.039999961853027)
Descriptors: MW 523.63, ALogP 8.55, HBA 4, HBD 0, PSA 42.68, QED 0.18
Compound (SMILES): CCOc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCNCC4)cc3)sc2n1
InChIKey: CMMQADPPZQOPCQ-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 425.56, ALogP 2.66, HBA 7, HBD 3, PSA 92.51, QED 0.54
Compound (SMILES): CCc1nc(N)nc(N)c1C#CC(C)c1cc2c(c(-c3ccncc3)c1)OCO2
InChIKey: BFKKZVMQJNNEFK-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0A017
Assay: Inhibition of TMP/methicillin-resistant Staphylococcus aureus recombinant DHFR H149R mutant expressed in Escherichia coli BL21 (DE3) cells assessed as oxidation of NADPH pre-incubated for 5 mins followed by dihydrofolate substrate addition
Measurement: Ki = 1363 nM (pChEMBL 5.869999885559082)
Descriptors: MW 387.44, ALogP 3.15, HBA 7, HBD 2, PSA 109.17, QED 0.66
Compound (SMILES): CNc1cc(Nc2cccn(-c3ccccn3)c2=O)nn2c(C(=O)N[C@@H]3C[C@@H]3F)cnc12
InChIKey: YITUGUNLCGLOII-GXTWGEPZSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 (unknown origin)
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 434.44, ALogP 1.9, HBA 9, HBD 3, PSA 118.24, QED 0.42
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCCN3Cc2ccc(F)c(Br)c2)n(C)c1=O
InChIKey: RYRWLXOBMISEDI-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB11 from recombinant human adenosine A3 receptor expressed in CHO cells
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 422.26, ALogP 1.75, HBA 7, HBD 0, PSA 65.06, QED 0.63
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCCCCC2)cc1
InChIKey: SZGBHOUXGOLUGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase-9 catalytic domain assessed as reduction in CO2 hydration after 15 mins by phenol red dye based stopped flow assay
Measurement: Ki = 16.8 nM (pChEMBL 7.78000020980835)
Descriptors: MW 282.37, ALogP 1.35, HBA 3, HBD 1, PSA 80.47, QED 0.89
Compound (SMILES): Cn1c(N2CCC(C)(CN)CC2)nc(N)c(Sc2cccc(Cl)c2Cl)c1=O
InChIKey: BHGFUFNIOHAHFW-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: SHP2 Allosteric Inhibition Assay: SHP2 is allosterically activated through binding of bis-tyrosyl-phosphorylated peptides to its Src Homology 2 (SH2) domains. The latter activation step leads to the release of the auto-inhibitory interface of SHP2, which in turn renders the SHP2 protein tyrosine phosphatase (PTP) active and available for substrate recognition and reaction catalysis. The catalytic activity of SHP2 was monitored using the surrogate substrate DiFMUP in a prompt fluorescence assay format.More specifically, the phosphatase reactions were performed at room temperature in 384-well black polystyrene plate, flat bottom, low flange, non-binding surface (Corning, Cat#3575) using a final reaction volume of 25 μL and the following assay buffer conditions: 60 mM HEPES, pH 7.2, 75 mM NaCl, 75 mM KCl, 1 mM EDTA, 0.05% P-20, 5 mM DTT.The inhibition of SHP2 by compounds of the invention (concentrations varying from 0.003-100 μM) was monitored using an assay in which 0.5 nM of SHP2 was incubated with of 0.5 μM of peptide IRS1_pY1172(dPEG8)pY1222 (sequence: H2N-LN(pY)IDLDLV(dPEG8)LST(pY)ASINFQK-amide) (SEQ ID NO:1). After 30-60 minutes incubation at 25° C., the surrogate substrate DiFMUP (Invitrogen, cat# D6567) was added to the reaction and incubated at 25° C. for 30 minutes. The reaction was then carefully diluted by the addition of 5 μL of a 160 μM solution of bpV(Phen) (Enzo Life Sciences cat# ALX-270-204). The fluorescence signal was monitored using a microplate reader (Envision, Perki-Elmer) using excitation and emission wavelengths of 340 nm and 450 nm, respectively. The inhibitor dose response curves were analyzed using normalized IC50 regression curve fitting with control based normalization.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 428.39, ALogP 3.39, HBA 7, HBD 2, PSA 90.17, QED 0.78
Compound (SMILES): C=Cc1ccc(S(=O)(=O)Nc2ccc3oc(-c4ccc(NS(=O)(=O)c5ccc(Cl)s5)cc4)nc3c2)cc1
InChIKey: BMFZKYPZQIDMPH-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P54829
Assay: Inhibition of human PTPN5 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 572.09, ALogP 6.45, HBA 7, HBD 2, PSA 118.37, QED 0.22
Compound (SMILES): O=c1cc(NCC(O)CN2CCN(c3nccc4ncccc34)CC2)c2cc(F)ccc2o1
InChIKey: LYIMJKFUHYOWBM-UHFFFAOYSA-N
Target: DNA topoisomerase 4 subunit A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0C1U9
Assay: Inhibition of Staphylococcus aureus ATCC 29213 DNA topoisomerase 4 subunit ParC assessed as reduction in decatenation of kinetoplast DNA incubated for 30 mins by ethidium bromide staining based gel electrophoresis method
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 449.49, ALogP 2.47, HBA 8, HBD 2, PSA 94.73, QED 0.43
Compound (SMILES): COc1cc2c(Oc3ccc(NC(=O)NS(=O)(=O)Cc4ccc(F)cc4)cc3F)ccnc2cc1OCCCN1CCCC1
InChIKey: OPMJBWVXRQIVBZ-UHFFFAOYSA-N
Target: Macrophage-stimulating protein receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q04912
Assay: Inhibition of RON (unknown origin) using poly (Glu, Tyr) 4:1 substrate incubated for 30 mins by HTRF assay
Measurement: IC50 = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 626.68, ALogP 5.83, HBA 8, HBD 2, PSA 119.09, QED 0.19
Compound (SMILES): COc1ccc(-c2nc(N3CCOCC3)sc2/C=C/C(=O)Nc2ccc(OC)c(OC)c2)cc1
InChIKey: FEOYEUYHQSHVNA-ZHACJKMWSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase12 preincubated for 10 mins followed by CO2 solution addition by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 481.57, ALogP 4.32, HBA 8, HBD 1, PSA 82.15, QED 0.48
Compound (SMILES): O=C(CCCCCCNC(=O)c1c(-c2ccc(O)cc2)sc2cc(O)ccc12)NO
InChIKey: YVLBUPXOCBVXFQ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) expressed in Escherichia coli using BML-KI-178 as substrate preincubated up to 3 hrs and measured after 35 mins by fluorescence assay
Measurement: IC50 = 719 nM (pChEMBL 6.139999866485596)
Descriptors: MW 428.51, ALogP 4.17, HBA 6, HBD 5, PSA 118.89, QED 0.2
Compound (SMILES): Cc1c(Br)ccc(Nc2cc(Cl)nc(SCC(=O)O)n2)c1C
InChIKey: BRXAIWWDESPYDF-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Activation of human Gal4-fused PPARalpha LBD transfected in HEK293T after 14 to 16 hrs by dual-glo luciferase reporter gene assay
Measurement: EC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 402.7, ALogP 4.43, HBA 5, HBD 2, PSA 75.11, QED 0.44
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2cc3c4c(c2)COc2cc(-c5cnc([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]5)cc(c2-4)OC3)[nH]1)C(C)C
InChIKey: VDKOVNUOEVQVSA-ACZARZSMSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A L31M mutant in HCV genotype 2a JFH1 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 9.85 nM (pChEMBL 8.010000228881836)
Descriptors: MW 794.91, ALogP 6.01, HBA 10, HBD 4, PSA 193.1, QED 0.15
Compound (SMILES): Cl.Clc1ccccc1OCc1cc(OC[C@@H]2CCCN2)no1
InChIKey: XPCHUQKFRLWOSK-MERQFXBCSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Displacement of [3H]nisoxetine from human NET expressed in HEK293 cells measured after 30 mins
Measurement: Ki = 2109 nM (pChEMBL 5.679999828338623)
Descriptors: MW 308.76, ALogP 3.04, HBA 5, HBD 1, PSA 56.52, QED 0.89
Compound (SMILES): COc1ccc(C2=NN(C(C)=O)C(c3ccc(OS(N)(=O)=O)cc3)C2)cc1
InChIKey: RHGAKHPDMOCLCI-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibitory constant incubated for 15 mins by phenol red dye based stopped flow assay
Measurement: Ki = 9.5 nM (pChEMBL 8.020000457763672)
Descriptors: MW 389.43, ALogP 1.98, HBA 6, HBD 1, PSA 111.29, QED 0.84
Compound (SMILES): CCc1cnc2c(N)c(C(=O)NCCc3ccc(N4CC5CCC(C4)N5)cc3)sc2n1
InChIKey: TVKGACZKSOSIKZ-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: Ubiquitin-Rhodamine 110 Assay for USP25 Activity: The assay was performed in a final volume of 9 μL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 μM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 μM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 μM. Final substrate (Ub-Rh110: Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub-Rh110]<<Km. 3 μL of 2× enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 μL of 2×Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 μL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 436.59, ALogP 2.75, HBA 7, HBD 3, PSA 96.17, QED 0.55
Compound (SMILES): Cc1nnc2n1-c1ccc(-c3cn[nH]c3)cc1C(Nc1ccc(Cl)cc1)CC2
InChIKey: UFFMFBORABJCTA-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Binding affinity to human recombinant BRD3 BD2 (306 to 417 residues) by fluorescence polarization assay
Measurement: Ki = 13.9 nM (pChEMBL 7.860000133514404)
Descriptors: MW 390.88, ALogP 4.72, HBA 5, HBD 2, PSA 71.42, QED 0.53
Compound (SMILES): O=C(CCCN1CCCN(c2ccccn2)CC1)c1ccc(F)cc1
InChIKey: YZWJNFUQGOYUQT-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement [3H]-DTG from sigma 2 receptor (unknown origin) expressed in HEK cell membranes
Measurement: Ki = 32 nM (pChEMBL 7.5)
Descriptors: MW 341.43, ALogP 3.4, HBA 4, HBD 0, PSA 36.44, QED 0.75
Compound (SMILES): Cn1cc2c(nc(NCCOCCOCCNC(=O)OC(C)(C)C)n3nc(-c4ccco4)nc23)n1
InChIKey: YSALKXWENFQKKA-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]-HEMADO from human adenosine A3 receptor expressed in CHO cells by radioligand competition analysis
Measurement: Ki = 585 nM (pChEMBL 6.230000019073486)
Descriptors: MW 486.53, ALogP 2.24, HBA 12, HBD 2, PSA 142.86, QED 0.3
Compound (SMILES): O=C1c2cc(-c3ccc(N4CCNCC4)cc3)ccc2Nc2ccc(F)cc2N1Cc1ccccc1
InChIKey: WUMWLAFRSNCXDX-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as reduction in cell growth incubated for 72 hrs in presence of 1 ug/ml Cetuximab by celltiter-glo luminescent cell viability assay
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 478.57, ALogP 5.81, HBA 4, HBD 2, PSA 47.61, QED 0.39
Compound (SMILES): C[C@@H]1CN2c3c(cc4c(N5CC6(CC6)OC5=O)noc4c3F)CC3(C(=O)NC(=O)NC3=O)[C@H]2[C@H](C)O1
InChIKey: QKEDBKFDVRJINN-KCWFYHRYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using tolbutamide as substrate preincubated for 10 mins followed by NADPH addition and measured for 15 mins by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 499.46, ALogP 1.35, HBA 9, HBD 2, PSA 143.31, QED 0.56
Compound (SMILES): Cc1ccc(CN2C(=O)/C(=N\c3ccc(NC(=O)Nc4ccc(S(N)(=O)=O)cc4)cc3)c3ccccc32)cc1
InChIKey: BATWGJOVDULBIQ-QVTSOHHYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 by stopped flow CO2 hydration assay
Measurement: Ki = 9.5 nM (pChEMBL 8.020000457763672)
Descriptors: MW 539.62, ALogP 4.95, HBA 5, HBD 3, PSA 133.96, QED 0.32
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCCC5(CCNC5)C4)cc3)sc2n1
InChIKey: CYCPONAUGISQIG-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 449.62, ALogP 3.74, HBA 6, HBD 3, PSA 83.28, QED 0.55
Compound (SMILES): Cc1cc(Cl)c2cc(C(=O)N[C@H](CO)c3ccc(S(=O)(=O)CC(=O)O)cc3)n(C)c2c1
InChIKey: IRYAJNZVJASVSQ-QGZVFWFLSA-N
Target: D-3-phosphoglycerate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: O43175
Assay: Inhibition of wild type PHGDH (unknown origin) preincubated for 30 mins followed by substrate addition and measured after 5 mins
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 464.93, ALogP 2.46, HBA 6, HBD 3, PSA 125.7, QED 0.49
Compound (SMILES): CCNCc1ccc(-c2cc(-c3nc(-c4ccc(S(=O)(=O)C(C)C)cc4)cnc3N)on2)cc1
InChIKey: ZVOIZFFFPDDJHJ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HCT116 cells assessed as reduction in histone H2AX phosphorylation by Hoechst staining-based immunofluorescence microscopic analysis
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 477.59, ALogP 4.34, HBA 8, HBD 2, PSA 124, QED 0.38
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(CC(=O)O)cc2)o1)[C@@H](CC)N(O)C=O
InChIKey: OOQSODFEUOWYPX-WOJBJXKFSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 487.55, ALogP 3.2, HBA 6, HBD 4, PSA 149.18, QED 0.1
Compound (SMILES): Clc1cnc(N[C@@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: XWKQZYOSWGEGIH-LLVKDONJSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 327.82, ALogP 3.44, HBA 4, HBD 3, PSA 65.63, QED 0.69
Compound (SMILES): NC[C@H](NC(=O)c1ccc(-c2ccc(C(F)(F)F)c(F)c2)[nH]1)c1nc(CO)cs1
InChIKey: ZKOITYDZLQYLNI-HNNXBMFYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human liver microsome CYP2C9 using diclofenac as substrate incubated for 20 mins by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 428.41, ALogP 3.22, HBA 5, HBD 4, PSA 104.03, QED 0.45
Compound (SMILES): COc1cccc(CCSc2ccc(NS(=O)(=O)N3CCN(c4ccc(C(C)(C)C)cc4)CC3)c(C(=O)O)c2)c1
InChIKey: UYWXDTRFWXMZPY-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Inhibition of N-terminal His6-tagged human Bcl-xL (with internal deletion of 45 to 85 amino acids and C-terminal truncation for 212 to 233 residues) expressed in Escherichia coli Rosetta2 DE3 by fluorescent labeled FAM-Bid peptide based fluorescence polarization assay
Measurement: Ki = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 583.78, ALogP 5.5, HBA 6, HBD 2, PSA 99.18, QED 0.3
Compound (SMILES): CC(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@@H](CC1CCCCC1)C(N)=O
InChIKey: IDNWCPOBBHGCML-SSUZURRFSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Full agonist activity at mouse MC5R expressed in HEK293 cells co-expressing CRE/beta-galactosidase reporter gene after 6 hrs by beta-galactosidase cAMP assay
Measurement: EC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 750.64, ALogP 0.48, HBA 7, HBD 7, PSA 231.26, QED 0.11
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)c(Cl)c1)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC)C(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N1CCC[C@H]1C(=O)N[C@H](C)C(=O)O
InChIKey: YVADPUXMVIIKCZ-RKMSMNQNSA-N
Target: Type-1 angiotensin II receptor A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25095
Assay: Agonist activity at rat AT1aR expressed in HEK293 cells incubated for 30 mins by IP1 accumulation assay
Measurement: EC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 960.53, ALogP -1.26, HBA 12, HBD 13, PSA 355.05, QED 0.03
Compound (SMILES): CC(=O)Oc1ccc(-c2cc3cccc(OC(C)=O)c3oc2=O)cc1OC(C)=O
InChIKey: ZNJRRUZTEADZNJ-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine receptor A2B expressed in CHO cells assessed as suppression of NECA-induced decrease of cAMP accumulation by Glo-sensor cAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 396.35, ALogP 3.24, HBA 8, HBD 0, PSA 109.11, QED 0.38
Compound (SMILES): CS(=O)(=O)Nc1ccc2oc(-c3ccc(NS(=O)(=O)c4ccc(Cl)s4)cc3)nc2c1
InChIKey: RWSPMGZHGVJTQR-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P54829
Assay: Inhibition of human PTPN5 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 483.98, ALogP 4.38, HBA 7, HBD 2, PSA 118.37, QED 0.42
Compound (SMILES): Cc1nc(-c2ccccc2)sc1C(=O)NC1CCCCC1
InChIKey: TZXKYABUDCYSOA-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Antagonist activity at N-terminal Flag epitope tagged CB2 (unknown origin) expressed in HTLA cells assessed as decrease in CP55940-induced beta-arrestin recruitment pretreated with non-selective cannabinoid receptor agonist CP55940 for 30 mins and measured after 20 mins by Tango assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 300.43, ALogP 4.18, HBA 3, HBD 1, PSA 41.99, QED 0.92
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N(C)CC4CCCNC4)cc3)sc2n1
InChIKey: ZTYWDJWORNMTEO-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 437.61, ALogP 3.6, HBA 6, HBD 3, PSA 83.28, QED 0.53
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(NC(C4CCC4)C4CCC4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: VQFKOPZALUTGKJ-BGIGGGFGSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [125I]N6-(4-amino-3-iodobenzyl)adenosine-5-N-methyluronamide from human A3A adenosine receptor expressed in CHO cell membranes after 60 mins by scintillation proximity assay
Measurement: Ki = 10600 nM (pChEMBL 4.96999979019165)
Descriptors: MW 389.46, ALogP 0.82, HBA 9, HBD 4, PSA 125.55, QED 0.57
Compound (SMILES): COCCN1CCO[C@@H](COc2cc(-c3cnc(OC)c(NS(C)(=O)=O)c3)cc3c2COC3)C1
InChIKey: ISMBMSPGDHMMNB-LJQANCHMSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant human full-length N-terminal His6-tagged p120gamma expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins in presence of biotin-PIP3 by HTRF assay
Measurement: IC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 493.58, ALogP 1.88, HBA 9, HBD 1, PSA 108.45, QED 0.53
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2cccc(OCCC)c2)o1)[C@@H](CC)N(O)C=O
InChIKey: OHNKBDIKCQUZSK-FGZHOGPDSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 487.6, ALogP 4.36, HBA 6, HBD 3, PSA 121.11, QED 0.11
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CCCCCCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: ZKZDXOKYTXAKHF-DSCYDBDCSA-N
Target: Neuropeptide Y receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Displacement of [3H]propionyl-pNPY from human NPY Y2 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ after 90 mins by liquid scintillation counting
Measurement: Ki > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 1590.9
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1cccc(-c2ncc(C)o2)c1
InChIKey: YQRPUCPLIICJIC-GOSISDBHSA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 416.48, ALogP 2.5, HBA 6, HBD 3, PSA 124.77, QED 0.16
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCNCC4)c(-c4cccc(Cl)c4)c3)sc2n1
InChIKey: LQZKOCKKMPXRLD-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Biochemical Assay: USP25: The assay was performed in a final volume of 9 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HC1, pH 8.0 solution; Corning 46-031-CM)), 3 mM BME (2-Mercaptoethanol; Sigma 63689-25ML-F), 0.03% BGG (0.22 uM filtered, Sigma, G7516-25G), and 0.01% Triton X-100 (Sigma, T9284-10L). Nanoliter quantities of 10-point, 3-fold serial dilution in DMSO was pre-dispensed into 1536 assay plates (Corning, #3724BC) for a final test concentration of 25 uM to 1.3 nM, top to lowest dose, respectively. Enzyme USP25, construct USP25-His6, (Boston Biochem E-546). Concentration and incubation times were optimized for the maximal signal-to-background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 75 pM. Final substrate (Ub -Rh110; Ubiquitin-Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub -Rh110]Â  Km. 3 uL of 2x enzyme was added to assay plates (pre-stamped with compound) preincubated with USP25 for 30 minutes and then 3 uL of 2x Ub-Rh110 was added to assay plates. Plates were incubated for 45 minutes at room temperature before addition of 3 uL of stop solution (final concentration of 10 mM citric acid (Sigma, 251275-500G)). Fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 506.08, ALogP 4.89, HBA 6, HBD 3, PSA 83.28, QED 0.35
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O
InChIKey: ZJBIJTQERSNYDX-PCBJKIODSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Agonist activity at human calcitonin receptor expressed in BHK570 cells assessed as increase in intracellular cAMP concentration incubated for 3 hrs in presence of 10% FBS by CRE luciferase reporter gene assay
Measurement: EC50 = 0.095 nM (pChEMBL 10.020000457763672)
Descriptors: MW 3658.17
Compound (SMILES): Oc1ccc2c(c1)CCCC(c1ccc3[nH]ccc3c1)=C2c1ccc(O[C@H]2CCN(CCCF)C2)cc1
InChIKey: QQKFOZPCEKQATC-NDEPHWFRSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Estrogen Receptor Coactivator Assay: It is a competition assay, where binding of a test compound to a complex comprised of (i) His6-ERα298-554 protein representing ERα ligand-binding domain, (ii) Tb-labeled His6 antibody, (iii) a fluorescein-labeled PGC1α coactivator peptide (EAEEPSLLKKLLLAPANTQ), and (iv) estradiol, results in a decrease of the TR-FRET signal due to dissociation of the coactivator peptide. His6-ERα298-554 proteins were expressed as WT or D538G or Y537S mutants in E. coli and purified by affinity chromatography. The assay works in a homogeneous mix-and-read format. In a typical experiment, a 4 μL mixture of 0.5 nM His6-ERα298-554, 0.5 nM Tb-labeled His6 antibody, 250 nM PGC1a peptide, and 3 nM estradiol in 100 mM potassium phosphate, pH 7.4, 0.01% Tween-20, 0.02% NaN3, 5 mM DTT, was added to 40 nL test compound in DMSO and incubated overnight at room temperature. The TR-FRET 520:495 nm emission ratio was calculated and used to determine the IC50 value from a dose response curve fit to the 4-parameter logistic equation. The antagonist activity with respect to estrogen receptors in this test is given by the concentration which inhibits 50% of the estrogen receptor activity (or IC50) in nM.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 496.63, ALogP 6.98, HBA 3, HBD 2, PSA 48.49, QED 0.29
Compound (SMILES): COc1ccc(C(=O)N2CCc3c([nH]c4ccccc34)C2c2ccc(Cl)c(Cl)c2)cc1
InChIKey: AKQFVWUCZTWDKB-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of human ABCG2 expressed in baculovirus infected Sf9 cell membrane assessed as inhibition of vanadate sensitive quercetin-stimulated ATPase activity after 20 mins by colorimetric method
Measurement: IC50 = 285 nM (pChEMBL 6.539999961853027)
Descriptors: MW 451.35, ALogP 6.27, HBA 2, HBD 1, PSA 45.33, QED 0.4
Compound (SMILES): COc1cc(-c2nc(NCc3ccc(/C=C/C(=O)NO)cc3)cc3c2[nH]c2ccccc23)cc(OC)c1OC
InChIKey: ZLYCLXZZARPMGZ-OUKQBFOZSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 using Boc-Lys (Ac)-AMC as substrate incubated for 60 mins and measured after 30 mins by fluorescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 524.58, ALogP 5.54, HBA 7, HBD 4, PSA 117.73, QED 0.11
Compound (SMILES): C(=N/c1c2c(nc3ccccc13)CCCC2)\c1cc(OCc2ccccc2)c(OCc2ccccc2)c(OCc2ccccc2)c1
InChIKey: HDBAZFWZBQLTKR-OOWNWPBNSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE assessed as dissociation constant for enzyme-substrate-inhibitor complex using butyrylthiocholine iodide as substrate measured for 125 secs by Ellman's method
Measurement: Ki = 192 nM (pChEMBL 6.71999979019165)
Descriptors: MW 604.75, ALogP 9.6, HBA 5, HBD 0, PSA 52.94, QED 0.14
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1cccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(C)c2)n1)[C@@H](CC)N(O)C=O.Cl
InChIKey: QHCSULSRIUITGX-HDFQZRMESA-N
Target: Tolloid-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L7
Assay: Inhibition of C-terminal Avi-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged recombinant human TLL2 (26 to 1015 amino acids) expressed in CHOE1A cells incubated for 60 mins with promyostatin peptide substrate by FRET based assay
Measurement: IC50 < 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 613.67, ALogP 2.34, HBA 8, HBD 6, PSA 215.33, QED 0.05
Compound (SMILES): Cc1ccccc1C(=O)N1C(=O)CC1CC(=O)O
InChIKey: QQGUOHQFMOOCJJ-UHFFFAOYSA-N
Target: Integrin alpha-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Binding affinity to alpha4beta1 integrin receptor (unknown origin) incubated for 1 hr by scintillation proximity binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 247.25, ALogP 1.21, HBA 3, HBD 1, PSA 74.68, QED 0.64
Compound (SMILES): CN(C1CCN(Cc2cc3nc(-c4cnc(N)nc4)nc(N4CCOCC4)c3s2)C1)S(C)(=O)=O
InChIKey: ALFGGTAMJAANKH-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using biotin-PIP3 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence polarization assay
Measurement: IC50 = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 504.64, ALogP 1.03, HBA 11, HBD 1, PSA 130.67, QED 0.52
Compound (SMILES): CCCNNC(=O)c1ccc(NCc2ccccc2)cc1
InChIKey: GHXAGWZSAKFQHQ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant HDAC6 (unknown origin) using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence based micro plate reader analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 283.38, ALogP 2.94, HBA 3, HBD 3, PSA 53.16, QED 0.54