lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COC(=O)c1ccc(N[C@@H]2C[C@H](C)N(C(C)=O)c3ccc(-c4cccc(NC(C)=O)c4)cc32)cc1
InChIKey: WEQSOZXIXPNDJW-MRDQGFSESA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to BDR2- BD2 (unknown origin) by TR-FRET assay
Measurement: Kd = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 471.56, ALogP 5.4, HBA 5, HBD 2, PSA 87.74, QED 0.49
Compound (SMILES): O=c1c(/C=N/Nc2ccc(C(F)(F)F)cc2)coc2c1ccc1oc(-c3ccc(Cl)cc3)cc12
InChIKey: LCMWUFLTMJGHMS-PNQUVVCRSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human AChE using acetylthiocholine as substrate preincubated for 15 mins followed by substrate addition and measured after 5 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 482.85, ALogP 7.32, HBA 5, HBD 1, PSA 67.74, QED 0.22
Compound (SMILES): CCOC(=O)C1=C(C)Cc2nc(N3CCC(C(=O)NS(=O)(=O)Cc4ccccc4)CC3)c(C#N)cc2C1
InChIKey: NLJJBXZIVNGFNU-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate preincubated for 10 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 522.63, ALogP 2.79, HBA 8, HBD 1, PSA 129.46, QED 0.55
Compound (SMILES): CN1CCN(CCCOC(=O)c2ccc3ccccc3c2)CC1
InChIKey: XGWTYMRRVDFIEO-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Binding affinity to human D3 receptor expressed in CHO cells assessed as inhibition constant by scintillation counting method
Measurement: Ki = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 312.41, ALogP 2.63, HBA 4, HBD 0, PSA 32.78, QED 0.63
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)cc2)c2cc[nH]c2c1=O
InChIKey: JGOZUFGBTSAWEI-NSCUHMNNSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged CECR2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 377.44, ALogP 3.05, HBA 4, HBD 1, PSA 67.33, QED 0.71
Compound (SMILES): CN1CCN(c2ncc3[nH]nc(-c4cnn(C)c4)c3n2)CC1=O
InChIKey: HEJWDMSZDBYDME-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: HTRF Assay (100 uM ATP): ALK2 (aa 147-end) was obtained from BPS biosciences. The enzymatic assays were conducted in white 384-well polystyrene plates in a final volume of 8 μL. The inhibitors were serially diluted in DMSO and added to the plate wells prior to addition of the other reaction components. The assays were carried out at 25° C. in the assay buffer (50 mM HEPES, pH 7.1, 10% Glycerol, 0.01% Brij50, 10 mM MgCl2, 1 mM EGTA, 5 mM DTT, and 0.01% BSA), containing 50 nM LANCE Ultra ULight-DNA Topoisomerase 2-alpha peptide (Perkin Elmer TRF0130), and 100 uM ATP. The final concentration of DMSO in the assay was 1% and the enzyme concentration was 2.5 nM for ALK2. The reactions were allowed to proceed for 2-4 hr after which, the reaction was quenched by addition of EDTA at a final concentration of 20 mM along with 1.5 nM LANCE Ultra Europium-anti-phospho-DNA Topoisomerase 2-alpha (Thr1342) antibody (Perkin Elmer TRF0218). The reaction was read on a PHERAstar FS plate reader (BMG Labtech). IC50 determination was performed by fitting percent control activity versus the log of the inhibitor concentration using the IDBS XLFit and GraphPad Prism 5.0 software.
Measurement: IC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 312.34, ALogP 0.03, HBA 7, HBD 1, PSA 95.83, QED 0.72
Compound (SMILES): CCCOc1c(CCC)cc(-c2ccccc2-c2nn[nH]n2)cc1NC(=O)Nc1ccc(C)cc1
InChIKey: UCPMUXOPKQHTIZ-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: IDO Kynurenine Assay: Human IDO1/HEK293 cells were seeded at 10,000 cells per 50 uL per well with RPMI/phenol red free media contains 10% FBS in a 384-well black wall clear bottom tissue culture plate (Matrix Technologies LLC) 125 nL of certain concentration of compound was then added to each well using ECHO liquid handling systems. The cells were incubated for 20 hours in 37° C. incubator with 5% CO2.The compound treatments were stopped by adding Trichloroacetic Acid (Sigma-Aldrich) to a final concentration at 0.2%. The cell plate was further incubated at 50° C. for 30 minute. The equal volume supernatant (20 uL) and 0.2% (w/v) Ehrlich reagent (4-dimethylaminobenzaldehyde, Sigma-Aldrich) in glacial acetic acid were mixed in a new clear bottom 384-well plate. This plate was then incubated at room temperature for 30 minute. The absorbance at 490 nm was measured on Envision plate reader.Compound IC50 values were calculated using the counts of 500 nM of a reference standard treatment as one hundred percent inhibition, and counts of no compound but DMSO treatment as zero percent inhibition.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 470.58, ALogP 6.23, HBA 5, HBD 3, PSA 104.82, QED 0.27
Compound (SMILES): CN1CCCC[C@H](N(c2cc(C#CC(C)(C)C)sc2C(=O)O)C(=O)[C@H]2CC[C@H](C)CC2)C1=O
InChIKey: KPNFBUNNEPDDOK-BJLQDIEVSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of human PXR expressed in human DPX2 co-expressing luciferase reporter gene incubated for 24 hrs by luciferase assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 472.65, ALogP 5.01, HBA 4, HBD 1, PSA 77.92, QED 0.62
Compound (SMILES): CC1CCCN1CCCOc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](N3CCCC3)CC[C@@H]12
InChIKey: BLISAYWDMSAMTN-OKSFETJPSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Displacement of N-alpha-[methyl-3H]-methylhistamine dihydrochloride from Sprague-Dawley rat brain membrane histamine H3 receptor assessed as inhibition constant incubated for 30 mins by liquid scintillation counting analysis
Measurement: Ki = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 450.71, ALogP 6.26, HBA 3, HBD 0, PSA 15.71, QED 0.48
Compound (SMILES): COc1cc2ncnc(NCCOc3ccccc3F)c2cc1OC
InChIKey: SQUSZMTZUQQFKO-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15303
Assay: Inhibition of ERBB4 (unknown origin)
Measurement: IC50 = 24200 nM (pChEMBL 4.619999885559082)
Descriptors: MW 343.36, ALogP 3.28, HBA 6, HBD 1, PSA 65.5, QED 0.66
Compound (SMILES): Cc1c(-c2cc(C#N)c(N)o2)c(=O)n(-c2ccccc2)n1C
InChIKey: QRZBWFJAYJYUJM-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19643
Assay: Inhibition of rat brain synaptosome MAO-B
Measurement: IC50 = 45.43 nM (pChEMBL 7.340000152587891)
Descriptors: MW 294.31, ALogP 2.2, HBA 6, HBD 1, PSA 89.88, QED 0.78
Compound (SMILES): COc1cccc(NC(=O)c2nnn(Cc3ccc(CN4CCOCC4)cc3)c2N)c1
InChIKey: DRHOOSHFHLLGDF-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 422.49, ALogP 2, HBA 8, HBD 2, PSA 107.53, QED 0.6
Compound (SMILES): C[C@@](N)(CO)CCc1ccc(OCc2ccc(Cl)c(Cl)c2)cc1
InChIKey: ZQQHXJCIFGMUPY-SFHVURJKSA-N
Target: Ceramide synthase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HA82
Assay: Inhibition of human CerS4
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 354.28, ALogP 4.21, HBA 3, HBD 2, PSA 55.48, QED 0.78
Compound (SMILES): CC[C@H]1CN(Cc2cc(C)cc(CC(=O)O)c2)CCN1c1nc2ccc(C(F)(F)F)cc2s1
InChIKey: ZBKXSRSXIGZPCY-IBGZPJMESA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Mus musculus
UniProt: P23204
Assay: Agonist activity at Gal4-fused mouse PPAR-alpha ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 477.55, ALogP 5.35, HBA 5, HBD 1, PSA 56.67, QED 0.52
Compound (SMILES): NC(=O)c1cnc(Nc2ccc(O)cn2)cc1Nc1ccccc1Cl
InChIKey: BDFXWFUXDCODKM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of GST-fused JAK3 (811 to 1124 residues) (unknown origin) using Carboxyfluorescein-Ahx-GGEEEEYFELVKKKK peptide as substrate incubated for 60 mins in presence of ATP by Janus kinase assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 355.79, ALogP 3.42, HBA 6, HBD 4, PSA 113.16, QED 0.56
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(=O)N3CCOCC3)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: FWTDDBIMDSVPTR-AATRIKPKSA-N
Target: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged TAF1 bromodomain 2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 451.52, ALogP 3.37, HBA 6, HBD 1, PSA 85.79, QED 0.58
Compound (SMILES): CN(C)c1ccc2c(-c3ccc(-c4cn(CCCCCn5cc(CCCCCN6CCC(COC(=O)Nc7ccc(F)cc7-c7ccc(F)c(Cl)c7)CC6)nn5)nn4)cc3C(=O)[O-])c3ccc(=[N+](C)C)cc-3oc2c1
InChIKey: PXHIFOLPKHLYBX-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M5 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 1039.63
Compound (SMILES): CNC(=O)CCCCC[C@H](NC(=O)Cn1ccc2cc(C#N)ccc21)c1ncc(-c2ccc(CN(C)C)cc2)[nH]1
InChIKey: WNBJBSFSPKVIPC-SANMLTNESA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of human HDAC4
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 539.68, ALogP 4.52, HBA 6, HBD 3, PSA 118.84, QED 0.22
Compound (SMILES): Cc1nc2c(N)cc(N3CCOCC3)nn2c1Cc1cccc(F)c1C1CCNCC1
InChIKey: QIDVCXQDTQASFN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00750
Assay: KINOMEscan Enzyme Binding Assays: Kinase enzyme binding affinities of compounds disclosed herein were determined using the KINOMEscan technology performed by DiscoveRx Corporation, San Diego, Calif., USA (www.kinomescan.com).
Measurement: Kd = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 424.52, ALogP 2.65, HBA 7, HBD 2, PSA 80.71, QED 0.67
Compound (SMILES): O=C1CN(Cc2ccc(C(=O)NO)cc2)C(=O)[C@@H](Cc2c[nH]c3ccccc23)N1
InChIKey: OUWQFNHQQZCXTJ-GOSISDBHSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of HDAC5 (unknown origin) using Fluor de lys as substrate by fluorescence based analysis
Measurement: IC50 = 4370 nM (pChEMBL 5.360000133514404)
Descriptors: MW 392.42, ALogP 1.36, HBA 4, HBD 4, PSA 114.53, QED 0.39
Compound (SMILES): C[C@@H]1OC(=O)NN=C1c1ccc(-c2ccc(F)cc2)c(C(F)(F)F)c1
InChIKey: JNTJTCXFIXNXDV-VIFPVBQESA-N
Target: cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (SINGLE PROTEIN), Homo sapiens
UniProt: Q14432
Assay: Inhibition of human full-length PDE3A expressed in Sf9 cells using [8-3H]adenosine 3', 5'-cyclic phosphate as substrate incubated for 60 mins by microbeta scintillation counting method
Measurement: IC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 352.29, ALogP 4.34, HBA 3, HBD 1, PSA 50.69, QED 0.82
Compound (SMILES): Cc1cc(CC(=O)O)cc(CN2CCN(c3nc4ccc(C(F)(F)F)cc4s3)C[C@H]2C)c1
InChIKey: HUAKZZAZJGNQFD-OAHLLOKOSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Mus musculus
UniProt: P23204
Assay: Agonist activity at Gal4-fused mouse PPAR-alpha ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 463.53, ALogP 4.96, HBA 5, HBD 1, PSA 56.67, QED 0.58
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3ccc(F)cc3F)nc2-c2ccc3[nH]ncc3c2)n1
InChIKey: SZPOIQZUDFAZMU-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 416.44, ALogP 5.21, HBA 4, HBD 3, PSA 82.28, QED 0.37
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)c(C#N)c2)c2cc(C)[nH]c2c1=O
InChIKey: BQAKOVGAYWUDIT-ONEGZZNKSA-N
Target: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged TAF1 bromodomain 2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 416.48, ALogP 3.23, HBA 5, HBD 1, PSA 91.12, QED 0.66
Compound (SMILES): O=C(CCCCCCNc1nc2ccccc2nc1-c1nc2ccccc2o1)NO
InChIKey: UPTYYNWPPBPUMA-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 44.74 nM (pChEMBL 7.349999904632568)
Descriptors: MW 405.46, ALogP 4.31, HBA 7, HBD 3, PSA 113.17, QED 0.22
Compound (SMILES): COc1ccc(/C=N/NC(=O)CCCCCCCC(=O)NO)cc1
InChIKey: GAZWXVIVAKKMPK-QGOAFFKASA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant His-tagged HDAC8 incubated for 20 mins by HDAC Glo assay
Measurement: IC50 = 60.32 nM (pChEMBL 7.21999979019165)
Descriptors: MW 335.4, ALogP 2.38, HBA 5, HBD 3, PSA 100.02, QED 0.25
Compound (SMILES): O=C1CCc2cc(OCCN3CCC[C@@H]3c3cccc(F)c3)ccc2N1
InChIKey: ZHGIASFMHGIOQA-HXUWFJFHSA-N
Target: Aldehyde dehydrogenase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P05091
Assay: Inhibition of full length human ALDH2 using propionaldehyde as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins in presence of NAD by luminescence microplate reader analysis
Measurement: IC50 >= 100000 nM (pChEMBL 4)
Descriptors: MW 354.43, ALogP 3.93, HBA 3, HBD 1, PSA 41.57, QED 0.88
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3ccc(=O)n(C4CCCCCC4)c3n2)CC1
InChIKey: NIVRVOZNYYXNJT-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: CDK6/Cyclin D1 Mobility Shift Assay: The purpose of the CDK6/Cyclin D1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) in the presence of small molecule inhibitors by using a fluorescence based microfluidic mobility shift assay. CDK6/Cyclin D1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide 5-FAM-Dyrktide (5-FAM-RRRFRPASPLRGPPK) (SEQ ID NO:2). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Typical reaction solutions contained 2% DMSO (± inhibitor), 10 mM MgCl2, 1 mM DTT, 2 mM ATP, 0.005% Tween 20 (TW-20), 3 μM 5-FAM-Dyrktide, 3 nM (active sites) CDK6/Cyclin D1 in 40 mM HEPES buffer at pH 7.5.Inhibitor Ki determinations for non-phosphorylated CDK6/CyclinD1 (LJIC-2003A2/1865) were initiated with the addition of ATP (50 μL final reaction volume), following a twelve minute pre-incubation of enzyme and inhibitor at 22° C. in the reaction mix. The reaction was stopped after 35 minutes by the addition of 50 μL of 25 mM EDTA. Ki determinations were made from a plot of the fractional velocity as a function of inhibitor concentration fit to the Morrison equation with the enzyme concentration as a variable.
Measurement: Ki = 0.96 nM (pChEMBL 9.020000457763672)
Descriptors: MW 419.55, ALogP 2.52, HBA 7, HBD 1, PSA 97.19, QED 0.77
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccc(-c5ccccc5)cc4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: DRUJOKCPVUXITN-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Trypanosoma congolense
UniProt: P13110
Assay: Inhibition of HIS-tagged recombinant Trypanosoma congolense TryR oxidoreductase activity expressed in Escherichia coli in the presence of NADPH by spectrophotometry based DTNB-coupled assay
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 622.82, ALogP 4.96, HBA 7, HBD 2, PSA 102.18, QED 0.13
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2cc(F)ccc2N2C[C@H]3C[C@@H]2CN3)n1
InChIKey: JKHBVOCOHYSWTQ-HUUCEWRRSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Inhibition of STK4 (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 437.45, ALogP 3.23, HBA 6, HBD 2, PSA 79.38, QED 0.64
Compound (SMILES): COc1cccc(Nc2cc(Nc3ccccc3Cl)c(C(N)=O)cn2)n1
InChIKey: QWJHDFPZYMYNPX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of GST-fused JAK3 (811 to 1124 residues) (unknown origin) using Carboxyfluorescein-Ahx-GGEEEEYFELVKKKK peptide as substrate incubated for 60 mins in presence of ATP by Janus kinase assay
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 369.81, ALogP 3.72, HBA 6, HBD 3, PSA 102.16, QED 0.61
Compound (SMILES): CCCC(=O)NCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.O=C(O)C(F)(F)F
InChIKey: OEBTWRYFDAUETA-ZMBIFBSDSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from human ERG expressed in CHO-K1 cell membrane measured after 45 mins by topcount scintillation counting method
Measurement: IC50 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 467.01, ALogP 4.02, HBA 5, HBD 1, PSA 67.23, QED 0.52
Compound (SMILES): CCC(=O)c1sc(-c2cccc(F)c2)nc1O
InChIKey: ANUOYWLYYBOAMH-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Inhibition of human TRPM8 expressed in HEK293 cells assessed as reduction in cold stimulated Ca2+ efflux preincubated for 5 mins followed by cold stimulation and measured for 3 mins
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 251.28, ALogP 3.25, HBA 4, HBD 1, PSA 50.19, QED 0.85
Compound (SMILES): Cn1cnc2c(c(-c3cc(Cl)c(O)c(C(N)=O)c3)cn2CC(=O)Nc2cc(N3CCOCC3)ncc2Cl)c1=O
InChIKey: LYPIBXVPZCTMSW-UHFFFAOYSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Surface Plasmon Resonance (SPR) Assay: SPR studies were performed using a Biacore™ T200 instrument (GE Health Sciences Inc.). The BCL6 BTB protein used in the FP assay was biotinylated using the site specific biotinylating enzyme BirA, and then cleaved with TEV protease to produce the BCL6 BTB domain (biotin-thrombin-BCL6 amino acids 1-129; 17 kd) that were use in SPR. This protein was stably captured (1000RU) to streptavidin coupled SA chips (BR-1005-31, GE Health Sciences Inc.) according to the manufacture's protocol. Compounds were dissolved in 100% DMSO at 10 mM and 2-fold serial dilutions were done in 100% DMSO. For SPR analysis the serially titrated compounds were diluted 1/20 into buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.05% Tween-20, 3 mM EDTA) giving a final concentration of 5% DMSO. The Biacore flow rate was set at 100 ul/min. For KD determinations, single cycle kinetic analysis was performed with an on time of 60 seconds, and an off time of 300 seconds. Curve fitting and KD calculations were done with the Biacore T200 Evaluation software (GE Health Sciences Inc).
Measurement: Kd = 16.2 nM (pChEMBL 7.789999961853027)
Descriptors: MW 572.41, ALogP 2.38, HBA 10, HBD 3, PSA 157.6, QED 0.32
Compound (SMILES): COc1cc(OC)c(Cl)c(-c2ccc3c(NC(=O)c4ccc(N5CCNC(C)(C)C5)cc4)n[nH]c3n2)c1Cl
InChIKey: QNXOYMFBIACDSL-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of N-terminal 6his tagged recombinant human FGFR2 N549H mutant (456 to 770 residues) expressed in baculovirus infected Sf21 cells by ELISA analysis
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 555.47, ALogP 5.39, HBA 7, HBD 3, PSA 104.4, QED 0.29
Compound (SMILES): O=c1c(/C=N/Nc2ccc(C(F)(F)F)cc2)coc2c1ccc1oc(-c3ccc(Cl)cc3)cc12
InChIKey: LCMWUFLTMJGHMS-PNQUVVCRSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of recombinant human BuChE using butyrylthiocholine as substrate preincubated for 15 mins followed by substrate addition and measured after 5 mins by Ellman's method
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 482.85, ALogP 7.32, HBA 5, HBD 1, PSA 67.74, QED 0.22
Compound (SMILES): CCOC(=O)C1=C(C)Cc2nc(N3CCC(C(=O)NS(=O)(=O)Cc4ccccc4)CC3)c(C#N)cc2C1
InChIKey: NLJJBXZIVNGFNU-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using Midazolam as substrate preincubated for 10 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 = 4280 nM (pChEMBL 5.369999885559082)
Descriptors: MW 522.63, ALogP 2.79, HBA 8, HBD 1, PSA 129.46, QED 0.55
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)cc2)c2cc[nH]c2c1=O
InChIKey: JGOZUFGBTSAWEI-NSCUHMNNSA-N
Target: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: Displacement of biotinylated small-molecule ligand from recombinant His-tagged TAF1 bromodomain 2 (unknown origin) measured after 10 mins by TR-FRET assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 377.44, ALogP 3.05, HBA 4, HBD 1, PSA 67.33, QED 0.71
Compound (SMILES): CN1CCN(c2ncc3[nH]nc(-c4cnn(C)c4)c3n2)CC1=O
InChIKey: HEJWDMSZDBYDME-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Enzymatic Assay: un-Phosphorylated (UP): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including un-phosphorylated (UP)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 312.34, ALogP 0.03, HBA 7, HBD 1, PSA 95.83, QED 0.72
Compound (SMILES): COc1cccc(NC(=O)c2nnn(Cc3ccc(CN4CCOCC4)cc3)c2N)c1
InChIKey: DRHOOSHFHLLGDF-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 422.49, ALogP 2, HBA 8, HBD 2, PSA 107.53, QED 0.6
Compound (SMILES): C[C@@](N)(CO)CCc1ccc(OCc2ccc(Cl)c(Cl)c2)cc1
InChIKey: ZQQHXJCIFGMUPY-SFHVURJKSA-N
Target: Ceramide synthase 5 (SINGLE PROTEIN), Mus musculus
UniProt: Q9D6K9
Assay: Inhibition of mouse CerS5
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 354.28, ALogP 4.21, HBA 3, HBD 2, PSA 55.48, QED 0.78
Compound (SMILES): CC[C@H]1CN(Cc2cc(C)cc(CC(=O)O)c2)CCN1c1nc2ccc(C(F)(F)F)cc2s1
InChIKey: ZBKXSRSXIGZPCY-IBGZPJMESA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Mus musculus
UniProt: P37238
Assay: Agonist activity at Gal4-fused mouse PPAR-gamma ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 477.55, ALogP 5.35, HBA 5, HBD 1, PSA 56.67, QED 0.52
Compound (SMILES): NC(=O)c1cnc(Nc2ccc(O)cn2)cc1Nc1ccccc1Cl
InChIKey: BDFXWFUXDCODKM-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of GST-fused Tyk2 (888 to 1187 residues) (unknown origin) using FITC-AhxKKSRGDYMTMQIG-NH2 peptide as substrate incubated for 60 mins in presence of ATP by Janus kinase assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 355.79, ALogP 3.42, HBA 6, HBD 4, PSA 113.16, QED 0.56
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(=O)N3CCOCC3)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: FWTDDBIMDSVPTR-AATRIKPKSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Binding affinity to ZsGreen fused-BRD9 (M1 to T597 residues) (unknown origin) expressed in human U2OS-C433 cells assessed as induction of protein bromodomain localization from chromatin by measuring formation of large nuclear puncta by fluorescence based assay
Measurement: EC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 451.52, ALogP 3.37, HBA 6, HBD 1, PSA 85.79, QED 0.58
Compound (SMILES): CNC(=O)CCCCC[C@H](NC(=O)Cn1ccc2cc(C#N)ccc21)c1ncc(-c2ccc(CN(C)C)cc2)[nH]1
InChIKey: WNBJBSFSPKVIPC-SANMLTNESA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of human HDAC5
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 539.68, ALogP 4.52, HBA 6, HBD 3, PSA 118.84, QED 0.22
Compound (SMILES): Cc1nc2c(N)cc(N3CCOCC3)nn2c1Cc1cccc(F)c1C1CCNCC1
InChIKey: QIDVCXQDTQASFN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: KINOMEscan Enzyme Binding Assays: Kinase enzyme binding affinities of compounds disclosed herein were determined using the KINOMEscan technology performed by DiscoveRx Corporation, San Diego, Calif., USA (www.kinomescan.com).
Measurement: Kd = 372 nM (pChEMBL 6.429999828338623)
Descriptors: MW 424.52, ALogP 2.65, HBA 7, HBD 2, PSA 80.71, QED 0.67
Compound (SMILES): O=C1CN(Cc2ccc(C(=O)NO)cc2)C(=O)[C@@H](Cc2c[nH]c3ccccc23)N1
InChIKey: OUWQFNHQQZCXTJ-GOSISDBHSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of HDAC7 (unknown origin) using Fluor de lys as substrate by fluorescence based analysis
Measurement: IC50 = 752 nM (pChEMBL 6.119999885559082)
Descriptors: MW 392.42, ALogP 1.36, HBA 4, HBD 4, PSA 114.53, QED 0.39
Compound (SMILES): Cc1cc(CC(=O)O)cc(CN2CCN(c3nc4ccc(C(F)(F)F)cc4s3)C[C@H]2C)c1
InChIKey: HUAKZZAZJGNQFD-OAHLLOKOSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Mus musculus
UniProt: P37238
Assay: Agonist activity at Gal4-fused mouse PPAR-gamma ligand binding domain expressed in CHO-K1 cells assessed as receptor transactivation incubated for 24 to 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 463.53, ALogP 4.96, HBA 5, HBD 1, PSA 56.67, QED 0.58
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3ccc(F)cc3F)nc2-c2ccc3[nH]ncc3c2)n1
InChIKey: SZPOIQZUDFAZMU-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 = 8700 nM (pChEMBL 5.059999942779541)
Descriptors: MW 416.44, ALogP 5.21, HBA 4, HBD 3, PSA 82.28, QED 0.37
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)c(C#N)c2)c2cc(C)[nH]c2c1=O
InChIKey: BQAKOVGAYWUDIT-ONEGZZNKSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Binding affinity to ZsGreen fused-BRD9 (M1 to T597 residues) (unknown origin) expressed in human U2OS-C433 cells assessed as induction of protein bromodomain localization from chromatin by measuring formation of large nuclear puncta by fluorescence based assay
Measurement: EC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 416.48, ALogP 3.23, HBA 5, HBD 1, PSA 91.12, QED 0.66
Compound (SMILES): O=C(CCCCCCNc1nc2ccccc2nc1-c1nc2ccccc2o1)NO
InChIKey: UPTYYNWPPBPUMA-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of HDAC11 (unknown origin)
Measurement: IC50 = 109.62 nM (pChEMBL 6.960000038146973)
Descriptors: MW 405.46, ALogP 4.31, HBA 7, HBD 3, PSA 113.17, QED 0.22
Compound (SMILES): COc1ccc(/C=N/NC(=O)CCCCCCCC(=O)NO)cc1
InChIKey: GAZWXVIVAKKMPK-QGOAFFKASA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of human recombinant His-tagged HDAC10 incubated for 20 mins by HDAC Glo assay
Measurement: IC50 = 11.05 nM (pChEMBL 7.960000038146973)
Descriptors: MW 335.4, ALogP 2.38, HBA 5, HBD 3, PSA 100.02, QED 0.25
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccc(-c5ccccc5)cc4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: DRUJOKCPVUXITN-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Inhibition of HIS-tagged recombinant human GR oxidoreductase activity expressed in Escherichia coli in the presence of NADPH by spectrophotometry based DTNB-coupled assay
Measurement: IC50 > 75000 nM (pChEMBL 4.125)
Descriptors: MW 622.82, ALogP 4.96, HBA 7, HBD 2, PSA 102.18, QED 0.13
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2cc(F)ccc2N2C[C@H]3C[C@@H]2CN3)n1
InChIKey: JKHBVOCOHYSWTQ-HUUCEWRRSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: HPK1 Kinase Binding Assay: A stock solution of 1 mM test compound was prepared in DMSO. The compound plate was prepared by 3-fold and 11-point serial dilutions. 0.1 μL of the compound in DMSO was transferred from the compound plate to the white 384 well polystyrene plates. The assay buffer contained 50 mM HEPES, pH 7.5, 0.01% Tween-20, 5 mM MgCl2, 0.01% BSA, and 5 mM DTT. 5 μL of 4 nM active HPK1 (SignalChem M23-11G) prepared in the buffer was added to the plate. The enzyme concentration given was based on the given stock concentration reported by the vender. 5 μl of 18 nM tracer 222 (ThermoFisher PV6121) and 4 nM LanthaScreen Eu-Anti GST antibody (ThermoFisher PV5595) were added. After one hour incubation at 25° C., the plates were read on a PHERAstar FS plate reader (BMG Labtech). Ki values were determined.
Measurement: Ki < 100 nM (pChEMBL 7)
Descriptors: MW 437.45, ALogP 3.23, HBA 6, HBD 2, PSA 79.38, QED 0.64
Compound (SMILES): COc1cccc(Nc2cc(Nc3ccccc3Cl)c(C(N)=O)cn2)n1
InChIKey: QWJHDFPZYMYNPX-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of GST-fused Tyk2 (888 to 1187 residues) (unknown origin) using FITC-AhxKKSRGDYMTMQIG-NH2 peptide as substrate incubated for 60 mins in presence of ATP by Janus kinase assay
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 369.81, ALogP 3.72, HBA 6, HBD 3, PSA 102.16, QED 0.61
Compound (SMILES): COc1cc(OC)c(Cl)c(-c2ccc3c(NC(=O)c4ccc(N5CCNC(C)(C)C5)cc4)n[nH]c3n2)c1Cl
InChIKey: QNXOYMFBIACDSL-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of N-terminal GST tagged recombinant human FGFR1 V561M mutant (456 to 765 residues) expressed in baculovirus infected Sf21 cells by ELISA analysis
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 555.47, ALogP 5.39, HBA 7, HBD 3, PSA 104.4, QED 0.29
Compound (SMILES): O=c1c(/C=N/Nc2ccc(C(F)(F)F)cc2)coc2c1ccc1oc(-c3ccc(Cl)cc3)cc12
InChIKey: LCMWUFLTMJGHMS-PNQUVVCRSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of COX2 (unknown origin) using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition by microplate spectrophotometric analysis
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 482.85, ALogP 7.32, HBA 5, HBD 1, PSA 67.74, QED 0.22
Compound (SMILES): CCOC(=O)C1=C(C)Cc2nc(N3CCC(C(=O)NS(=O)(=O)Cc4ccccc4)CC3)c(C#N)cc2C1
InChIKey: NLJJBXZIVNGFNU-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate preincubated for 10 mins followed by NADPH addition and measured after 15 mins by LC-MS/MS analysis
Measurement: IC50 = 3640 nM (pChEMBL 5.440000057220459)
Descriptors: MW 522.63, ALogP 2.79, HBA 8, HBD 1, PSA 129.46, QED 0.55
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)cc2)c2cc[nH]c2c1=O
InChIKey: JGOZUFGBTSAWEI-NSCUHMNNSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: Binding affinity to ZsGreen fused-BRD9 (M1 to T597 residues) (unknown origin) expressed in human U2OS-C433 cells assessed as induction of protein bromodomain localization from chromatin by measuring formation of large nuclear puncta by fluorescence based assay
Measurement: EC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 377.44, ALogP 3.05, HBA 4, HBD 1, PSA 67.33, QED 0.71
Compound (SMILES): CN1CCN(c2ncc3[nH]nc(-c4cnn(C)c4)c3n2)CC1=O
InChIKey: HEJWDMSZDBYDME-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: Phosphorylated (P): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including phosphorylated (P)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 312.34, ALogP 0.03, HBA 7, HBD 1, PSA 95.83, QED 0.72
Compound (SMILES): COc1cccc(NC(=O)c2nnn(Cc3ccc(CN4CCOCC4)cc3)c2N)c1
InChIKey: DRHOOSHFHLLGDF-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: EC50 > 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 422.49, ALogP 2, HBA 8, HBD 2, PSA 107.53, QED 0.6
Compound (SMILES): C[C@@](N)(CO)CCc1ccc(OCc2ccc(Cl)c(Cl)c2)cc1
InChIKey: ZQQHXJCIFGMUPY-SFHVURJKSA-N
Target: Ceramide synthase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6ZMG9
Assay: Inhibition of human CerS6
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 354.28, ALogP 4.21, HBA 3, HBD 2, PSA 55.48, QED 0.78
Compound (SMILES): NC(=O)c1cnc(Nc2ccc(O)cn2)cc1Nc1ccccc1Cl
InChIKey: BDFXWFUXDCODKM-UHFFFAOYSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 in human M07E cells assessed as reduction of IL-15 stimulated STAT phosphorylation preincubated for 30 mins followed by IL-15 stimulation for 15 mins by flow cytometry method
Measurement: IC50 = 218 nM (pChEMBL 6.659999847412109)
Descriptors: MW 355.79, ALogP 3.42, HBA 6, HBD 4, PSA 113.16, QED 0.56
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(=O)N3CCOCC3)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: FWTDDBIMDSVPTR-AATRIKPKSA-N
Target: ATPase family AAA domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6PL18
Assay: Binding affinity to human partial length ATAD2A (Q981 to R1108 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 451.52, ALogP 3.37, HBA 6, HBD 1, PSA 85.79, QED 0.58
Compound (SMILES): CNC(=O)CCCCC[C@H](NC(=O)Cn1ccc2cc(C#N)ccc21)c1ncc(-c2ccc(CN(C)C)cc2)[nH]1
InChIKey: WNBJBSFSPKVIPC-SANMLTNESA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of human HDAC7
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 539.68, ALogP 4.52, HBA 6, HBD 3, PSA 118.84, QED 0.22
Compound (SMILES): Cc1nc2c(N)cc(N3CCOCC3)nn2c1Cc1cccc(F)c1C1CCNCC1
InChIKey: QIDVCXQDTQASFN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: KINOMEscan Enzyme Binding Assays: Kinase enzyme binding affinities of compounds disclosed herein were determined using the KINOMEscan technology performed by DiscoveRx Corporation, San Diego, Calif., USA (www.kinomescan.com).
Measurement: Kd = 5012 nM (pChEMBL 5.300000190734863)
Descriptors: MW 424.52, ALogP 2.65, HBA 7, HBD 2, PSA 80.71, QED 0.67
Compound (SMILES): O=C1CN(Cc2ccc(C(=O)NO)cc2)C(=O)[C@@H](Cc2c[nH]c3ccccc23)N1
InChIKey: OUWQFNHQQZCXTJ-GOSISDBHSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of HDAC9 (unknown origin) using Fluor de lys as substrate by fluorescence based analysis
Measurement: IC50 = 2560 nM (pChEMBL 5.590000152587891)
Descriptors: MW 392.42, ALogP 1.36, HBA 4, HBD 4, PSA 114.53, QED 0.39
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)c(C#N)c2)c2cc(C)[nH]c2c1=O
InChIKey: BQAKOVGAYWUDIT-ONEGZZNKSA-N
Target: Bromodomain-containing protein 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H8M2
Assay: IC50 measurements for inhibitors using BRD9 AlphaLisa Binding Assay: His/Flag epitope tagged BRD9134-239 was cloned, expressed, and purified to homogeneity. BRD9 binding and inhibition was assessed by monitoring the engagement of biotinylated H4-tetraacetyl peptide (New England Peptide, NEP2069-11/13) with the target using the AlphaLisa technology (Perkin-Elmer). Specifically, in a 384 well ProxiPlate BRD9 (50 nM final) was combined with peptide (3 nM final) in 50 mM HEPES (pH 7.5), 150 mM NaCl, 1 mM TCEP, 0.01% (w/v) BSA, and 0.008% (w/v) Brij-35 either in the presence of DMSO (final 0.8% DMSO) or compound dilution series in DMSO. After 20 minutes incubation at room temperature AlphaLisa Streptavidin Acceptor Beads (Perkin-AL125C) and AlphaLisa Nickel donor beads (Perkin AS 10 ID) were added to a final concentration of 15 ug/mL each. After ninety minutes of equilibration in the dark, the plates were read on an Envision instrument and IC50s calculated using a four parameter non-linear curve fit.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 416.48, ALogP 3.23, HBA 5, HBD 1, PSA 91.12, QED 0.66
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccc(-c5ccccc5)cc4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: DRUJOKCPVUXITN-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Leishmania infantum
UniProt: A4HSF7
Assay: Mixed non-competitive inhibition of Leishmania infantum TryR using TS2 as substrate assessed as inhibition constant of first equilibrium by plot analysis
Measurement: Ki = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 622.82, ALogP 4.96, HBA 7, HBD 2, PSA 102.18, QED 0.13
Compound (SMILES): COc1cccc(Nc2cc(Nc3ccccc3Cl)c(C(N)=O)cn2)n1
InChIKey: QWJHDFPZYMYNPX-UHFFFAOYSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 in human M07E cells assessed as reduction of IL-15 stimulated STAT phosphorylation preincubated for 30 mins followed by IL-15 stimulation for 15 mins by flow cytometry method
Measurement: IC50 = 169 nM (pChEMBL 6.769999980926514)
Descriptors: MW 369.81, ALogP 3.72, HBA 6, HBD 3, PSA 102.16, QED 0.61
Compound (SMILES): COc1cc(OC)c(Cl)c(-c2ccc3c(NC(=O)c4ccc(N5CCNC(C)(C)C5)cc4)n[nH]c3n2)c1Cl
InChIKey: QNXOYMFBIACDSL-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) by ELISA method
Measurement: IC50 = 51.4 nM (pChEMBL 7.289999961853027)
Descriptors: MW 555.47, ALogP 5.39, HBA 7, HBD 3, PSA 104.4, QED 0.29
Compound (SMILES): O=c1c(/C=N/Nc2ccc(C(F)(F)F)cc2)coc2c1ccc1oc(-c3ccc(Cl)cc3)cc12
InChIKey: LCMWUFLTMJGHMS-PNQUVVCRSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of human LOX5 using arachidonic acid preincubated for 10 mins followed by substrate addition by microplate spectrophotometric analysis
Measurement: IC50 = 29000 nM (pChEMBL 4.539999961853027)
Descriptors: MW 482.85, ALogP 7.32, HBA 5, HBD 1, PSA 67.74, QED 0.22
Compound (SMILES): C/C=C/Cn1cc(-c2ccc(C(=O)N3CCOCC3)cc2)c2cc[nH]c2c1=O
InChIKey: JGOZUFGBTSAWEI-NSCUHMNNSA-N
Target: ATPase family AAA domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6PL18
Assay: Binding affinity to human partial length ATAD2A (Q981 to R1108 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 377.44, ALogP 3.05, HBA 4, HBD 1, PSA 67.33, QED 0.71
Compound (SMILES): CN1CCN(c2ncc3[nH]nc(-c4cnn(C)c4)c3n2)CC1=O
InChIKey: HEJWDMSZDBYDME-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Enzymatic Assay: un-Phosphorylated (UP): The inhibitor potency of the exemplified compounds was determined in an enzyme discontinuous assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.2 μL was transferred to the wells of a 384-well plate. For the isoforms of FGFR (−1, −2, −3 wild-type and mutant isoforms, −4) including un-phosphorylated (UP)proteins, a 5 μL/well volume of enzyme diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated with inhibitor for 5 to 15 minutes at ambient temperature. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The reaction was initiated by the addition of a 5 μL/well volume containing both biotinylated EQEDEPEGDYFEWLE (SEQ ID: 1) peptide substrate and ATP in assay buffer. The 10 μL/well reaction concentration of the peptide substrate was 500 nM whereas the ATP concentration was maintained near or below the ATP Km for each FGFR isoform. The ATP Km values were pre-determined for each FGFR isoform in a separate series of experiments. The reaction plate was incubated at 25° C. for 1 hr and the reactions were ended with the addition of 5 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 45 mM EDTA, 600 nM staurosporin, with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for −10 minutes at ambient temperature before scanning on a PheraStar plate reader (BMG Labtech) instrument.
Measurement: IC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 312.34, ALogP 0.03, HBA 7, HBD 1, PSA 95.83, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(=O)N3CCOCC3)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: FWTDDBIMDSVPTR-AATRIKPKSA-N
Target: ATPase family AAA domain-containing protein 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULI0
Assay: Binding affinity to human partial length ATAD2B (Q955 to R1082 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 451.52, ALogP 3.37, HBA 6, HBD 1, PSA 85.79, QED 0.58
Compound (SMILES): Cc1nc2c(N)cc(N3CCOCC3)nn2c1Cc1cccc(F)c1C1CCNCC1
InChIKey: QIDVCXQDTQASFN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: KINOMEscan Enzyme Binding Assays: Kinase enzyme binding affinities of compounds disclosed herein were determined using the KINOMEscan technology performed by DiscoveRx Corporation, San Diego, Calif., USA (www.kinomescan.com).
Measurement: Kd > 30200 nM (pChEMBL 4.519999980926514)
Descriptors: MW 424.52, ALogP 2.65, HBA 7, HBD 2, PSA 80.71, QED 0.67
Compound (SMILES): O=C1CN(Cc2ccc(C(=O)NO)cc2)C(=O)[C@@H](Cc2c[nH]c3ccccc23)N1
InChIKey: OUWQFNHQQZCXTJ-GOSISDBHSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of HDAC10 (unknown origin) incubated for 1 hr by TR-FRET analysis
Measurement: IC50 = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 392.42, ALogP 1.36, HBA 4, HBD 4, PSA 114.53, QED 0.39
Compound (SMILES): C[n+]1nn(-c2ccc(-c3nc(CCc4ccc(-c5ccccc5)cc4)cs3)c(OCCN3CCNC3=O)c2)cc1CCCCN.O=C(O)C(F)(F)F.O=S(=O)([O-])C(F)(F)F
InChIKey: DRUJOKCPVUXITN-UHFFFAOYSA-N
Target: Trypanothione reductase (SINGLE PROTEIN), Leishmania infantum
UniProt: A4HSF7
Assay: Mixed non-competitive inhibition of Leishmania infantum TryR using TS2 as substrate assessed as inhibition constant of two-step induced-fit mechanism by plot analysis
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 622.82, ALogP 4.96, HBA 7, HBD 2, PSA 102.18, QED 0.13