lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1CCC(c2ccc(Nc3ncc4c(=O)n(C5CCCC5)n(-c5cccc(C(C)(C)O)n5)c4n3)cc2)CC1
InChIKey: DGXWMXHFEWCJTP-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of WEE1 in human U2OS cells incubated for 1 hr by mesoscale discovery assay
Measurement: IC50 = 387 nM (pChEMBL 6.409999847412109)
Descriptors: MW 527.67, ALogP 4.87, HBA 9, HBD 2, PSA 101.1, QED 0.37
Compound (SMILES): O=C(NS(=O)(=O)C1CC1)c1cc(Cl)c(OCCC2(F)CCN(Cc3cc(Cl)cc(Cl)c3)CC2)cc1F
InChIKey: VOOKXELDQCVPST-UHFFFAOYSA-N
Target: Sodium channel protein type 4 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35499
Assay: Inhibition of Nav1.4 (unknown origin) by whole-cell patch clamp assay
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 581.9, ALogP 5.78, HBA 5, HBD 1, PSA 75.71, QED 0.41
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)C[C@@H]1CCCN1C
InChIKey: MILBIPKHYWBIPY-QFIPXVFZSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR Exon 19 Deletion and Exon 20 T790M Concurrent Mutations: A compound's ability in selectively inhibiting EGFR exon 19 deletion and T790M concurrent mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with EGFR exon 19 deletion and T790M mutation. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR E746-A750 deletion and T790M Mutation, was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR exon 19 deletion and T790M mutations. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR E746-A750 deletion and T790M Mutation virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing EGFR E746-A750 deletion and T790M Mutation (named Ba/F3-EGFR-Del/T790M) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-EGFR-Del/T790M cells seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega; this assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives). Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 611.75, ALogP 5.61, HBA 10, HBD 2, PSA 113.85, QED 0.17
Compound (SMILES): Cc1cn(-c2cccc(C(F)(F)F)c2)c2ccc(C(=O)NS(C)(=O)=O)cc12
InChIKey: WRSMYUAIFIUQIQ-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.5/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 27000 nM (pChEMBL 4.570000171661377)
Descriptors: MW 396.39, ALogP 3.65, HBA 4, HBD 1, PSA 68.17, QED 0.73
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3ccc(Cl)c(Cl)c3)nc2-c2ccc3[nH]ncc3c2)n1
InChIKey: SJAUZFKPCNJCLQ-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 449.35, ALogP 6.24, HBA 4, HBD 3, PSA 82.28, QED 0.3
Compound (SMILES): COCCOc1nc2c(nc1C#N)C(=O)c1ccccc1-2
InChIKey: YMUQPZVRIVWORD-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P40818
Assay: Inhibition of USP8 (unknown origin)
Measurement: IC50 = 53000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 281.27, ALogP 1.58, HBA 6, HBD 0, PSA 85.1, QED 0.67
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(N[C@@H]3CCOC3=O)c2C#N)cc1
InChIKey: UDLNTFXZFUPQKN-JOCHJYFZSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 assessed as reduction in PI4,5P2 production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 2 mM ATP by HTRF assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 450.5, ALogP 4.96, HBA 7, HBD 1, PSA 97.13, QED 0.41
Compound (SMILES): O=C(Nc1cccc(-n2cc(CNc3ccc(N4CCC(O)CC4)c(C(=O)N4CCCCC4)c3)nn2)c1)c1cc(F)cc(F)c1
InChIKey: AWMIUMADZIDOLF-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-MET (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 615.69, ALogP 5, HBA 8, HBD 3, PSA 115.62, QED 0.26
Compound (SMILES): Cc1noc(C)c1-c1ccc2[nH]c(=O)cc(NCc3ccccc3)c2c1
InChIKey: ZZEQMSXTKAJTLH-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) by fluorescence based assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 345.4, ALogP 4.41, HBA 4, HBD 2, PSA 70.92, QED 0.57
Compound (SMILES): NC1CCN(c2c(-c3cc(Cl)cc(Cl)c3)cnc3ccccc23)CC1
InChIKey: LQQAGKUKYRVPHN-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Agonist activity at human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 372.3, ALogP 5.14, HBA 3, HBD 1, PSA 42.15, QED 0.68
Compound (SMILES): CCn1nnc(-c2sc(-c3cccc(F)c3)nc2O)n1
InChIKey: HOVUYEIYKRUBIF-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 = 21.4 nM (pChEMBL 7.670000076293945)
Descriptors: MW 291.31, ALogP 2.33, HBA 7, HBD 1, PSA 76.72, QED 0.8
Compound (SMILES): CCC(=O)NCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.O=C(O)C(F)(F)F
InChIKey: VNTNAMBVXPTMQO-VEIFNGETSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Antagonist activity against recombinant human adrenergic alpha1B receptor expressed in CHO cells incubated for 30 mins by FLIPR analysis
Measurement: Ki = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 452.99, ALogP 3.63, HBA 5, HBD 1, PSA 67.23, QED 0.57
Compound (SMILES): Cc1cccc(Nc2cc(Nc3ccccc3Cl)c(C(N)=O)cn2)n1
InChIKey: OYWNKAAPXTYEBN-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 30 mins in presence of ATP by caliper microfluidic mobility shift assay
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 353.81, ALogP 4.02, HBA 5, HBD 3, PSA 92.93, QED 0.64
Compound (SMILES): COc1cccc2ccc(C(=O)NCc3ccc(C(=O)NO)cc3)nc12
InChIKey: PKWQVPMUGMNEBZ-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) using Boc-Lys(Ac)-AMC or Boc-Lys(Tfa)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 1 hr by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 351.36, ALogP 2.29, HBA 5, HBD 3, PSA 100.55, QED 0.48
Compound (SMILES): O=C(Nc1cnccc1-c1ccccc1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: LJUDIYPNWBIDNH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK (unknown origin) by Ambit kinase assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 358.4, ALogP 3.74, HBA 4, HBD 2, PSA 83.98, QED 0.73
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(-c4ccnc(N5CCOCC5)c4)c3c2)C(C)(C)n2nnnc2N1C
InChIKey: VTISWVCQZDZSAV-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant expressed in HEK293 cells assessed as reduction in pSer935 phosphorylation incubated for 2 hrs by HTRF analysis
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 500.57, ALogP 2.55, HBA 10, HBD 2, PSA 129.98, QED 0.43
Compound (SMILES): Cc1cn(-c2ccc(F)cc2)c2ccc(C(=O)NS(C)(=O)=O)cc12
InChIKey: ZHYFENVYUKWFHL-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human Nav1.5/beta1/2 transfected in HEK293-A cells assessed as inhibition of channel current incubated for 5.5 mins by high-throughput electrophysiology system analysis
Measurement: IC50 = 42000 nM (pChEMBL 4.380000114440918)
Descriptors: MW 346.38, ALogP 2.77, HBA 4, HBD 1, PSA 68.17, QED 0.79
Compound (SMILES): CN(CCCCCCCCCCCCn1cc(C=O)c2cc(O)ccc21)Cc1cccc(O)c1
InChIKey: FSMMMQWAIKAMQM-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Mixed type inhibition of human BuChE assessed as inhibition constant using butyrylthiocholine iodide as substrate by lineweaver-burk plot analysis
Measurement: Ki = 1770 nM (pChEMBL 5.75)
Descriptors: MW 464.65, ALogP 6.9, HBA 5, HBD 2, PSA 65.7, QED 0.18
Compound (SMILES): CC1CN1c1cc(O)c2nc(N)sc2c1
InChIKey: PHBIAWCGMOCBGF-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase NSD3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZ95
Assay: Inhibition of NSD3 (unknown origin)
Measurement: IC50 = 14300 nM (pChEMBL 4.840000152587891)
Descriptors: MW 221.28, ALogP 1.79, HBA 5, HBD 2, PSA 62.15, QED 0.72
Compound (SMILES): O=C[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@@H]1[C@H]2CCC[C@H]2CN1C(=O)COc1ccc(Cl)cc1Cl
InChIKey: HKJKOHDJUKCNRG-ZEAPZOAHSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of recombinant SARS-CoV-2 3CLp using fluorogenic substrate by microplate reader
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 496.39, ALogP 2.21, HBA 5, HBD 2, PSA 104.81, QED 0.54
Compound (SMILES): Cc1onc(-c2ccccc2)c1C(=O)NCCCCCNC(=O)[C@H](C)S
InChIKey: IMIDYBQMXWFUIG-AWEZNQCLSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human full length recombinant HDAC6 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 375.49, ALogP 2.98, HBA 5, HBD 3, PSA 84.23, QED 0.46
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cncc(Cl)c3c(N[C@H](CC)C(N)=O)c2C#N)cc1
InChIKey: QFMIEIPPPNOUGA-OAQYLSRUSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of recombinant full length His-tagged PIP4K2A (unknown origin) expressed in sf21 assessed as reduction in PI4,5P2 production preincubated for 20 mins followed by substrate addition and measured after 60 mins using Dic8-PI5P as substrate in presence of 2 mM ATP by HTRF assay
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 485.98, ALogP 5.56, HBA 6, HBD 2, PSA 113.92, QED 0.34
Compound (SMILES): CC1CN(c2ccncc2NC(=O)c2ccnn3cc(-c4ccccc4)nc23)CCO1
InChIKey: MENVSADYTLLXLP-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Inhibition of CDK5 (unknown origin)
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 414.47, ALogP 3.27, HBA 7, HBD 1, PSA 84.65, QED 0.55
Compound (SMILES): Fc1ccc(OC[C@@H]2CN(Cc3cn4ccccc4n3)CCO2)cc1F
InChIKey: IYPLGFSKAOXCFI-INIZCTEOSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 91.2 nM (pChEMBL 7.039999961853027)
Descriptors: MW 359.38, ALogP 2.89, HBA 5, HBD 0, PSA 39, QED 0.7
Compound (SMILES): CN1CCN(C(=O)CCCN2CCN(c3cccc(Cl)c3Cl)CC2)C(C(=O)NC2CCCCC2)C1
InChIKey: WZVSGKQRSIHTAZ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Partial agonist activity at human D2 receptor expressed in HEK293T cells assessed as beta-arrestin recruitment preincubated for 10 mins with coelenterazine followed by compound addition and measured after 10 mins by BRET assay
Measurement: EC50 = 3.631 nM (pChEMBL 8.4399995803833)
Descriptors: MW 524.54, ALogP 3.49, HBA 5, HBD 1, PSA 59.13, QED 0.59
Compound (SMILES): Cc1csc(OC[C@@H]2CN(Cc3cc4ccc(Cl)cc4[nH]3)CCO2)n1
InChIKey: HDDVHPLBIKYRCZ-INIZCTEOSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 169.82 nM (pChEMBL 6.769999980926514)
Descriptors: MW 377.9, ALogP 3.87, HBA 5, HBD 1, PSA 50.38, QED 0.73
Compound (SMILES): CC(C)n1nc(-c2nnc(C3CCN(C4CCC4)CC3)o2)c2ccccc21.O=C(O)C(=O)O
InChIKey: BAUQVAHEEFXWCX-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate incubated for 12 mins in presence of NADPH regenerating system by LC-MS/MS analysis
Measurement: IC50 = 37000 nM (pChEMBL 4.429999828338623)
Descriptors: MW 365.48, ALogP 4.4, HBA 6, HBD 0, PSA 59.98, QED 0.69
Compound (SMILES): Cc1cc(N2CCN(C(=O)c3ccc(C(C)(C)C)cc3)CC2)nc(N2CCCC2)n1
InChIKey: QJZSBJRVAIZDFO-UHFFFAOYSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Inhibition of GCase in patient derived fibroblast cells using 5'pentafluorobenzoylaminofluorescein-di-beta-D-glucoside as substrate assessed as substrate hydrolysis by FACS analysis
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 407.56, ALogP 3.65, HBA 5, HBD 0, PSA 52.57, QED 0.78
Compound (SMILES): COc1ccc(-c2cc3cc4c(=O)c(C=O)coc4cc3o2)cc1
InChIKey: XAYKMQRPZRNJNL-UHFFFAOYSA-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 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 320.3, ALogP 4.03, HBA 5, HBD 0, PSA 69.65, QED 0.53
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2cccc(Cl)c2)CCC1(O)c1cccc(O)c1
InChIKey: OUHGHFXEMHKVJE-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at MOR (unknown origin) expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding measured after 60 mins by liquid scintillation counting analysis
Measurement: EC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 402.92, ALogP 2.89, HBA 4, HBD 2, PSA 64.01, QED 0.81
Compound (SMILES): O=C1CN(Cc2ccc(C(=O)NO)cc2)C(=O)[C@H](Cc2c[nH]c3ccccc23)N1
InChIKey: OUWQFNHQQZCXTJ-SFHVURJKSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of full length C-terminal His/FLAG tagged human recombinant HDAC1 (1 to 482 residues) expressed in baculovirus-infected Sf9 cells using RHK-K(Ac)-AMC as substrate incubated for 2 hrs
Measurement: IC50 = 405 nM (pChEMBL 6.389999866485596)
Descriptors: MW 392.42, ALogP 1.36, HBA 4, HBD 4, PSA 114.53, QED 0.39
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCCNC(=O)[C@H](CCC(=O)O)NC(=O)c1ccc(N(C)Cc2cnc3nc(N)nc(N)c3n2)cc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)[C@@H](C)CC
InChIKey: CKBSFTZJAYRRQQ-USSPWNEHSA-N
Target: Neuropeptide Y receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Agonist activity at human Y2R expressed in myo-[2-3H]-inositol labelled African green monkey COS7 cells coexpressing chimeric Galphadelta6qi4myr protein assessed as accumulation of [2-3H]-IP after 1 hr by scintillation counting analysis
Measurement: EC50 = 209 nM (pChEMBL 6.679999828338623)
Descriptors: MW 4734.29
Compound (SMILES): C=CC(=O)N1CC[C@H](c2nc(-c3cc4cc(Br)cc(OC)c4s3)c3c(N)nccn23)C1
InChIKey: ZYBQELLBNQSEEB-LBPRGKRZSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human recombinant FGFR4
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 498.41, ALogP 4.47, HBA 7, HBD 1, PSA 85.75, QED 0.42
Compound (SMILES): Cc1cc(N2CCOCC2)cnc1NC(=O)c1cc(C(=O)NCc2ccc(F)c(F)c2)c(F)cc1Cl
InChIKey: GBAXCPGBQNNUHB-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Inverse agonist activity at human PPARgamma expressed in CHO cells co-expressing GAL4-NHR-LBD assessed as transcriptional repression preincubated for 6 hrs followed by luciferin addition by luminescence method
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 518.92, ALogP 4.48, HBA 5, HBD 2, PSA 83.56, QED 0.5
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CO)NC(=O)/C=N/OCc1ccc(S(N)(=O)=O)cc1)C(=O)N1CCC[C@H]1C(N)=O
InChIKey: CIYDWUJZZVUIJH-LBURKSJTSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as inhibition constant
Measurement: Ki = 9600 nM (pChEMBL 5.019999980926514)
Descriptors: MW 554.63, ALogP -1.68, HBA 9, HBD 5, PSA 223.58, QED 0.14
Compound (SMILES): Cc1noc(-c2ccccc2)c1C#CCCCCNC(=O)C(C)(C)S
InChIKey: VHNISSUREJJHQB-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human full length recombinant HDAC6 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 356.49, ALogP 4, HBA 4, HBD 2, PSA 55.13, QED 0.47
Compound (SMILES): CN(C)c1cccc2c(SNCCCCCC(=O)NO)cccc12
InChIKey: IOJSHUPVMUJFRE-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of HDAC4 (unknown origin)
Measurement: IC50 = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 347.48, ALogP 3.57, HBA 5, HBD 3, PSA 64.6, QED 0.28
Compound (SMILES): O=C1[C@@H]2Cc3c([nH]c4ccccc34)[C@@H](c3ccc4c(c3)OCO4)N2C(=O)CN1CCC1CCN(Cc2ccccc2)CC1
InChIKey: KVANOXIAOYTXBY-ZBWWXOROSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of PDE5A1 (unknown origin) using FAM-cGMP as substrate incubated for 60 mins by IMAP-fluorescence polarization assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 576.7, ALogP 4.88, HBA 5, HBD 1, PSA 78.11, QED 0.35
Compound (SMILES): COc1cc(/C=c2\c(=O)[nH]n3c(=O)c4ccccc4nc23)cc(OC)c1OC
InChIKey: SBBHTKBJRAVMMH-JYRVWZFOSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX (unknown origin)
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 379.37, ALogP 1.11, HBA 7, HBD 1, PSA 94.92, QED 0.57
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3[nH]ncc3c2)n1
InChIKey: FXWMKOAMGUIHEX-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 8600 nM (pChEMBL 5.070000171661377)
Descriptors: MW 398.45, ALogP 5.07, HBA 4, HBD 3, PSA 82.28, QED 0.39
Compound (SMILES): C=CC(=O)N1CCC[C@H](n2nc(-c3ccc(Oc4ccccc4)cc3C)c3c(N)ncnc32)C1
InChIKey: BJMXICGJKUALLN-SFHVURJKSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Inhibition of BMX (unknown origin) by Z'LYTE assay
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 454.53, ALogP 4.53, HBA 7, HBD 1, PSA 99.16, QED 0.45
Compound (SMILES): CC(C)C[C@H]1CN(c2nc3ccc(Cl)cc3s2)CCC1CCOc1cc(CC(=O)O)ccc1Cl
InChIKey: QJANOKPCWNKQDB-GGYWPGCISA-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 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 521.51, ALogP 7.19, HBA 5, HBD 1, PSA 62.66, QED 0.32
Compound (SMILES): CC1(C)C(/C=C/C=C/C=C2/N(CCCCS(=O)(=O)O)c3ccccc3C2(C)C)=[N+](CCCCCC(=O)NCCCCCCCCN2CCC(OC(=O)Nc3ccc(F)cc3-c3ccc(F)c(Cl)c3)CC2)c2ccc(S(=O)(=O)[O-])cc21
InChIKey: BMNOFIWIZFZYES-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M4 receptor expressed in human HEK293T cell membranes by radioligand competition binding based analysis
Measurement: Ki = 0.87 nM (pChEMBL 9.0600004196167)
Descriptors: MW 1160.89
Compound (SMILES): COc1cccc(/C=C/C(=O)NC[C@@H](Cc2ccccc2)NS(=O)(=O)c2ccc(Br)cc2)c1
InChIKey: YOLVZOJWYFHBDZ-RCJYHZQCSA-N
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Inhibition of human cathepsin K
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 529.46, ALogP 4.18, HBA 4, HBD 2, PSA 84.5, QED 0.39
Compound (SMILES): CCn1c(=O)c2ccnn2c2cc(N(C)C)c(C(=O)NCc3cccnc3)cc21
InChIKey: OXBZWMNEKIHBRX-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 PIP2:PS as substrate preincubated for 1 hr followed by ATP and substate addition and measured after 1 hr by ADP-glo reagent based assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 390.45, ALogP 2.06, HBA 7, HBD 1, PSA 84.53, QED 0.56
Compound (SMILES): O=c1cc(CO)n(-c2c(Cl)cccc2Cl)c2c(Cl)cnc(OC[C@@H](O)CO)c12
InChIKey: DDDSGZFENQKDDY-JTQLQIEISA-N
Target: Potassium voltage-gated channel subfamily KQT member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51787
Assay: Inhibition of recombinant human KCNQ1
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 445.69, ALogP 2.57, HBA 7, HBD 3, PSA 104.81, QED 0.54
Compound (SMILES): Cc1cc(C)cc(-c2cncc(C(=O)Nc3cccc(O)c3)c2NCCCN)c1
InChIKey: NUUWLGXOHGOZLE-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Agonist activity at human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 390.49, ALogP 4.08, HBA 5, HBD 4, PSA 100.27, QED 0.46
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)C1CN(C)C1)c1ncc(-c2cc3ccccc3nc2OC)o1
InChIKey: YOCBGMVQRJHNRU-QHCPKHFHSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human HDAC6
Measurement: IC50 = 177 nM (pChEMBL 6.75)
Descriptors: MW 478.59, ALogP 4.55, HBA 7, HBD 1, PSA 97.56, QED 0.38
Compound (SMILES): Cc1ccc(CC(=O)O)cc1OCCN1CCN(c2nc3ccc(Cl)cc3s2)C[C@@H]1C
InChIKey: WGVWBIUWHHDYCY-INIZCTEOSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Mus musculus
UniProt: P35396
Assay: Agonist activity at Gal4-fused mouse PPAR-delta 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 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 460, ALogP 4.47, HBA 6, HBD 1, PSA 65.9, QED 0.56
Compound (SMILES): COc1ccc(/C=C2\SC(=O)N(CCNC(=O)Nc3c(C)n(C)n(-c4ccccc4)c3=O)C2=O)cc1
InChIKey: ADQLECAYDOTLPN-HKWRFOASSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) by ELISA assay
Measurement: IC50 = 258 nM (pChEMBL 6.590000152587891)
Descriptors: MW 507.57, ALogP 3.35, HBA 8, HBD 2, PSA 114.67, QED 0.47
Compound (SMILES): Cc1cccc(C)c1N1C(=O)c2ccc(C(=O)OCc3cn(-c4ccc(S(N)(=O)=O)cc4)nn3)cc2C1=O
InChIKey: OZUYYULYXSVVHQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human transmembrane carbonic anhydrase 9 using 4-nitrophenyl acetate as substrate assessed as inhibition constant by spectrophotometric analysis
Measurement: Ki = 24.46 nM (pChEMBL 7.610000133514404)
Descriptors: MW 531.55, ALogP 2.69, HBA 9, HBD 1, PSA 154.55, QED 0.29
Compound (SMILES): NC(=O)c1cnc(Nc2cccc(O)n2)cc1Nc1ccccc1Cl
InChIKey: PYJOHIHCMNCVLZ-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of AuroraA (unknown origin)
Measurement: IC50 > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 355.79, ALogP 3.42, HBA 6, HBD 4, PSA 113.16, QED 0.56
Compound (SMILES): COc1ccc2c(c1)c(C=O)cn2CCCCCCCCN(C)Cc1cccc(O)c1
InChIKey: OIIHAUYKICHNQI-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using ATCI and BTCI as substrate preincubated for 5 mins followed by substrate addition and measured after 3 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 2150 nM (pChEMBL 5.670000076293945)
Descriptors: MW 422.57, ALogP 5.64, HBA 5, HBD 1, PSA 54.7, QED 0.29
Compound (SMILES): O=C1NCCc2ccc(cc2)Nc2nccc(n2)Nc2cc1[nH]n2
InChIKey: JZFLSWUCZKXSQQ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of N-terminal NanoLuc-fused full length intact GSK3B (unknown origin) transfected in HEK293T cells incubated for 2 hrs in presence of tracer K8 by NanoBRET assay
Measurement: IC50 = 34000 nM (pChEMBL 4.46999979019165)
Descriptors: MW 321.34, ALogP 1.97, HBA 6, HBD 4, PSA 107.62, QED 0.5
Compound (SMILES): COc1cccc(F)c1-c1nccc(C(=O)Nc2cc(F)c3c(cnn3C)c2N2CC[C@@H](N)C2)n1
InChIKey: PSZVRCRTXCCMNS-CYBMUJFWSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin) incubated for 90 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 479.49, ALogP 3.11, HBA 8, HBD 2, PSA 111.19, QED 0.45
Compound (SMILES): C[C@@]1(O)CCC[C@H]1n1c(=O)c(Cl)cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: PFGMZHAOYLGYMA-DNVCBOLYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/cyclin E1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 455.97, ALogP 1.76, HBA 8, HBD 2, PSA 117.42, QED 0.72
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)[C@@H](C)CC
InChIKey: FLIJYNCTNKGDAO-YKHRJRMHSA-N
Target: Neuropeptide Y receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49146
Assay: Agonist activity at human Y2R expressed in myo-[2-3H]-inositol labelled African green monkey COS7 cells coexpressing chimeric Galphadelta6qi4myr protein assessed as accumulation of [2-3H]-IP after 1 hr by scintillation counting analysis
Measurement: EC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 4253.71
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3ccc(=O)n(C4CCCC4)c3n2)CC1
InChIKey: PPTJJWQOPWUCOH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: CDK2/Cyclin E1 Mobility Shift Assay: The purpose of the CDK2/Cyclin E1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) of small molecule inhibitors by using a fluorescence-based microfluidic mobility shift assay. CDK2/Cyclin E1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide FL-Peptide-18 (5-FAM-QSPKKG-CONH2) (SEQ ID NO:1). (CPC Scientific, Sunnyvale, Calif.). 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. Wild-type full length CDK2/wild-type full length Cyclin E1 enzyme complex was produced in-house (baculoviral expression, LJIC-2080/LJIC-2103) and phosphorylated by CDK7/Cyclin H1/Mat1 enzyme complex with CDK2:CDK7 ratio of 50:1 (concentration mg/mL) in the presence of 10 mM MgCl2 and 5 mM ATP at room temperature for one hour. Typical reaction solutions (50 μL final reaction volume) contained 2% DMSO (± inhibitor), 4 mM MgCl2, 1 mM DTT, 150 μM ATP (ATP Km=67.4 μM), 0.005% Tween-20, 3 μM FL-Peptide-18, and 0.36 nM (catalytically competent active site) phosphorylated wild-type full length CDK2/Cyclin E1 enzyme complex in 25 mM HEPES buffer at pH 7.15. The assay was initiated with the addition of ATP, following a fifteen minutes pre-incubation of enzyme and inhibitor at room temperature in the reaction mixture. The reaction was stopped after 45 minutes at room temperature by the addition of 50 μL of 80 mM EDTA, pH 7.5. The Ki value was determined from the fit of the data to the Morrison tight-binding competitive inhibition equation with the enzyme concentration as a variable.
Measurement: Ki = 0.71 nM (pChEMBL 9.149999618530273)
Descriptors: MW 391.5, ALogP 1.74, HBA 7, HBD 1, PSA 97.19, QED 0.85
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(OC)c(CCC)c(OC)c4)nn32)CC1
InChIKey: VZOSDPVVDDOWFT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubated for 3 hrs by HTRF-based analysis
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 481.6, ALogP 3.4, HBA 7, HBD 2, PSA 111.71, QED 0.56
Compound (SMILES): CN(C)c1nc(-c2cccc(F)c2)c(C(=O)Nc2ccc3c(c2)CCC(=O)N3)s1
InChIKey: UPJMHXMNZZSWQM-UHFFFAOYSA-N
Target: Retinal dehydrogenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O94788
Assay: Inhibition of full length human ALDH1A2 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 = 1000 nM (pChEMBL 6)
Descriptors: MW 410.47, ALogP 4.15, HBA 5, HBD 2, PSA 74.33, QED 0.68
Compound (SMILES): Cc1noc(-c2cccc(F)c2)c1C#CCCCCCNC(=O)C(C)S
InChIKey: ZSCLWKQWMCNIJI-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human full length recombinant HDAC6 expressed in baculovirus infected Sf9 cells using RHKKAc as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 2 hrs by fluorescence based analysis
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 374.48, ALogP 4.14, HBA 4, HBD 2, PSA 55.13, QED 0.44
Compound (SMILES): O=C(CCCCCCN(Cc1cc2ccccc2[nH]1)Cc1cc2ccccc2[nH]1)NO
InChIKey: XIBGZRVNDWMMFE-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 expressed in Escherichia coli BL21 (DE3) cells by using Boc-L-Lys(Ac)-AMC as substrate measured after 24 hrs by fluorescence based analysis
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 418.54, ALogP 5.11, HBA 3, HBD 4, PSA 84.15, QED 0.16
Compound (SMILES): COc1cccc(S(=O)(=O)N(Cc2ccc(NS(=O)(=O)O)cc2)c2nc(-c3ccccc3)cs2)c1
InChIKey: DLTQFAVGKLFIEF-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of recombinant TC-PTP (unknown origin)
Measurement: IC50 = 31260 nM (pChEMBL 4.5)
Descriptors: MW 531.64, ALogP 4.43, HBA 7, HBD 2, PSA 125.9, QED 0.31
Compound (SMILES): CC(Nc1ncnc(N)c1C#N)c1cc2ncc(Cl)n2nc1-c1ccccc1
InChIKey: WKDBRCUUDXLTIM-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Transcreener KINASE Assay: Briefly, the Transcreener KINASE Assay was designed as a simple two-part, endpoint assay as follows:1) Preparation of 25 uL kinase reaction: the 25 uL kinase reaction was performed by preparing a reaction mixture containing 10 uL kinase buffer (50 mM HEPES, 100 mM NaCl, 1 mM EGTA, 0.03% CHAPS, 3 mM MgCl2, and freshly supplemented 1 mM DTT), and 10 uL 30 uM PIP2 and 10 uM ATP, 5 uL test compound solution (the compound was dissolved in DMSO, the final concentrations of the compound in the reaction mixture were at 1 uM, 0.3 uM, 0.1 uM, 0.037 uM, 0.012 uM, 0.0041 uM, 0.0014 uM and 0.0005 uM, and final concentration of DMSO in the reaction mixture was 2%) or 5 uL control (2% DMSO). The reaction mixture was added into desired wells of a 96-well plate. The plate was sealed and incubated for 80 min at room temperature.2) Next, 25 uL ADP detection mix was added into each well. The plate was sealed again and incubated for 60 min at room temperature. Then fluorescence polarization was measured by Tecan Infinite F500 Reader.Data was analyzed and IC50 values were generated using the add-in software for Microsoft Excel, Xlfit (version 5.3).
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 390.84, ALogP 3.47, HBA 8, HBD 2, PSA 117.81, QED 0.55
Compound (SMILES): Cc1ccc(NC(=O)Nc2cc(-c3ccccc3-c3nn[nH]n3)cc3c2OCC=CC3c2ccccc2)cc1
InChIKey: ROPDQICAVLKEAY-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 514.59, ALogP 6.57, HBA 5, HBD 3, PSA 104.82, QED 0.23
Compound (SMILES): COCCNC(=O)CCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.Cl
InChIKey: FSPHHEQOLOPZPH-VZYDHVRKSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Antagonist activity against recombinant human adrenergic alpha1B receptor expressed in CHO cells incubated for 30 mins by FLIPR analysis
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 497.04, ALogP 3.65, HBA 6, HBD 1, PSA 76.46, QED 0.41
Compound (SMILES): Cn1ccc(=O)c(O)c1C(=O)NCc1ccc(-c2ccccc2)cc1
InChIKey: FSEDMHXJLQVYKB-UHFFFAOYSA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of human MMP-13
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 334.38, ALogP 2.69, HBA 4, HBD 2, PSA 71.33, QED 0.77
Compound (SMILES): O=c1cc(CO)n(-c2c(Cl)cccc2Cl)c2c(Cl)cnc(OC[C@H](O)CO)c12
InChIKey: DDDSGZFENQKDDY-SNVBAGLBSA-N
Target: Potassium voltage-gated channel subfamily KQT member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51787
Assay: Inhibition of recombinant human KCNQ1
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 445.69, ALogP 2.57, HBA 7, HBD 3, PSA 104.81, QED 0.54
Compound (SMILES): C=CC(=O)N1CCC(C2CCNc3c(C(N)=O)c(-c4cc(Cl)c(Br)c(OC)c4)nn32)CC1
InChIKey: ZMCYWNHBOFVQPF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubated for 3 hrs by HTRF-based analysis
Measurement: IC50 = 28.2 nM (pChEMBL 7.550000190734863)
Descriptors: MW 522.83, ALogP 3.85, HBA 6, HBD 2, PSA 102.48, QED 0.58
Compound (SMILES): CCCCc1nc2c(N)nc3ccccc3c2s1
InChIKey: XQXNQKAEROQGAD-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at TLR8 (unknown origin)
Measurement: EC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 257.36, ALogP 3.77, HBA 4, HBD 1, PSA 51.8, QED 0.78
Compound (SMILES): CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CN3CCN(C(=O)C4CCC4)CC3=O)n(C)c2n1
InChIKey: ZGZMQKJLWFWWDG-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of human PI3Kgamma in presence of [p32-gamma]-ATP measured after 2 hrs by hotspot assay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 557.66, ALogP 2.07, HBA 10, HBD 0, PSA 114.51, QED 0.35
Compound (SMILES): COc1ccc(S(=O)(=O)N(C)c2c(C)cc(Cc3ccc(CN(C)C)cc3)cc2C(=O)NO)cc1
InChIKey: AYTZJEWKGLEPFF-UHFFFAOYSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Homo sapiens
UniProt: P78536
Assay: Inhibition of TACE (unknown origin)
Measurement: IC50 = 243 nM (pChEMBL 6.610000133514404)
Descriptors: MW 497.62, ALogP 3.6, HBA 6, HBD 2, PSA 99.18, QED 0.35
Compound (SMILES): CN(C)CC1CN(C(=O)Cc2ccc(Cl)cc2)CCC1(O)c1cccc(O)c1
InChIKey: WAPQGYPGSJNYQW-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at MOR (unknown origin) expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding measured after 60 mins by liquid scintillation counting analysis
Measurement: EC50 = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 402.92, ALogP 2.89, HBA 4, HBD 2, PSA 64.01, QED 0.81
Compound (SMILES): Cc1cc(C(=O)NC2Nc3cccc(C)c3N2[C@H]2CCCCN(C(=O)/C=C/CN(C)C)C2)ccn1
InChIKey: WFAOJPLNRNZXIN-LXARNSNTSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant human CLK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 5962 nM (pChEMBL 5.21999979019165)
Descriptors: MW 476.63, ALogP 3.14, HBA 6, HBD 2, PSA 80.81, QED 0.62
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OCC(C)C)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: PDHCFKKUVBCBBI-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: HER2 Exon 20 YVMA Insertion Mutation: A compound's ability in selectively inhibiting Her2 exon 20 YVMA insertion mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with Her2 Exon20 YVMA insertions. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR exon 20 insertions YVMA (A775_G776ins YVMA), was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR exon 20 insertions. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR Exon20 virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing Her2 Exon20 YVMA insertions (named Ba/F3-Her2 Exon20 YVMA) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-Her2 Exon20 YVMA cells seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega; this assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives). Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 599.74, ALogP 5.32, HBA 10, HBD 2, PSA 113.85, QED 0.16
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(C(=O)OC(C)C)c(-c3cn(C)c4ccccc34)n2)c(OC)cc1N(C)C[C@@H]1CCCN1C
InChIKey: MILBIPKHYWBIPY-QFIPXVFZSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR Exon 21 L858R and Exon 20 T790M Concurrent Mutations: A compound's ability in selectively inhibiting EGFR L858R and T790M concurrent mutations can be assessed using Ba/F3 cells, a murine pro-B cell line, which have been transduced with EGFR L858R and T790M double mutations. An expression vector, pLVX-IRES puro (Clontech) coding for human EGFR L858R and T790M double mutation, was transfected into HEK293 cells by the Trans-Lentiviral ORF Packaging System (Thermo Scientific), to produce virus encoding EGFR L858R and T790M double mutations. Ba/F3 (DSMZ) cells maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 200 μM L-glutamine/200 μg/mL penicillin/200 μg/mL streptomycin (Life Technology) and 10 ng/mL IL-3 (R&D system), were infected by EGFR L858R and T790M double mutation virus and subsequently selected by puromycin (Life Technology) selection and IL-3 depletion. Ba/F3 cells expressing EGFR L858R and T790M double mutation (named Ba/F3-EGFR L858R/T790M) can proliferate in the absence of IL-3. The anti-proliferative activity of compounds was determined as follows: BaF3-EGFR L858R/T790M cells seeded in 96 well plates (2500 cells/well) were treated with test compound (dissolved in DMSO) at a series of concentrations (4-fold dilution, top concentration: 10,000 nM). The plates were incubated for 72 h in a 37° C. incubator with 5% CO2, and the number of viable cells in each well were measured indirectly by CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega; this assay is a colorimetric method for determining the number of viable cells through measurement of their metabolic activity by detection of enzymatic conversion of tetrazolium salts into blue formazan derivatives). Reagent (20 μL) was added into each well, and the plates were returned to the incubator for 2 h. The absorbance in each well was then measured at 490 nm using an Envision plate reader (Perkin Elmer). IC50 values were calculated by determining the concentration of compound required to decrease the MTS signal by 50% comparing to the DMSO control in best-fit curves using Microsoft XLfit software or Accelrys Pipeline Pilot.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 611.75, ALogP 5.61, HBA 10, HBD 2, PSA 113.85, QED 0.17
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3ccc(Cl)c(Cl)c3)nc2-c2ccc3[nH]ncc3c2)n1
InChIKey: SJAUZFKPCNJCLQ-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 449.35, ALogP 6.24, HBA 4, HBD 3, PSA 82.28, QED 0.3
Compound (SMILES): CCOc1ccccc1-c1ccc(-c2nc3cnccc3c(N[C@@H]3CCOC3=O)c2C#N)cc1
InChIKey: UDLNTFXZFUPQKN-JOCHJYFZSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of human PIP4K2A in human THP-1 cells assessed as increase in Akt phosphorylation at Ser473 residue incubated for 2 hrs by HTRF assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 450.5, ALogP 4.96, HBA 7, HBD 1, PSA 97.13, QED 0.41
Compound (SMILES): Cc1noc(C)c1-c1ccc2[nH]c(=O)cc(NCc3ccccc3)c2c1
InChIKey: ZZEQMSXTKAJTLH-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) by fluorescence based assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 345.4, ALogP 4.41, HBA 4, HBD 2, PSA 70.92, QED 0.57
Compound (SMILES): CCn1nnc(-c2sc(-c3cccc(F)c3)nc2O)n1
InChIKey: HOVUYEIYKRUBIF-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 decrease in outward currents by patch clamp electrophysiology method
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 291.31, ALogP 2.33, HBA 7, HBD 1, PSA 76.72, QED 0.8
Compound (SMILES): CCC(=O)NCCN1CCC[C@@H]1Cn1nc(Cc2ccc(Cl)cc2)c2ccccc2c1=O.O=C(O)C(F)(F)F
InChIKey: VNTNAMBVXPTMQO-VEIFNGETSA-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 = 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 452.99, ALogP 3.63, HBA 5, HBD 1, PSA 67.23, QED 0.57
Compound (SMILES): Cc1cccc(Nc2cc(Nc3ccccc3Cl)c(C(N)=O)cn2)n1
InChIKey: OYWNKAAPXTYEBN-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-Ahr-KKSRGDYMTMQIG-NH2 peptide as substrate incubated for 30 mins in presence of ATP by caliper microfluidic mobility shift assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 353.81, ALogP 4.02, HBA 5, HBD 3, PSA 92.93, QED 0.64
Compound (SMILES): O=C(Nc1cnccc1-c1ccccc1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: LJUDIYPNWBIDNH-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of FMS (unknown origin) by Ambit kinase assay
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 358.4, ALogP 3.74, HBA 4, HBD 2, PSA 83.98, QED 0.73
Compound (SMILES): CC1=C(C(=O)Nc2ccc3[nH]nc(-c4ccnc(N5CCOCC5)c4)c3c2)C(C)(C)n2nnnc2N1C
InChIKey: VTISWVCQZDZSAV-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human wild type LRRK2 expressed in HEK293 cells assessed as reduction in pSer935 phosphorylation incubated for 2 hrs by immunoblotting analysis
Measurement: IC50 = 259 nM (pChEMBL 6.590000152587891)
Descriptors: MW 500.57, ALogP 2.55, HBA 10, HBD 2, PSA 129.98, QED 0.43