lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H]1CC[C@@H](Oc2cc(C#N)ccn2)CN1C(=O)c1ccccc1-c1ncccn1
InChIKey: MMRBNOXAAQLWLU-SJLPKXTDSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56719
Assay: FLIPR Ca2+ Flux Assay: Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine. All reagents were from GIBCO-Invitrogen Corp. The seeded plates are incubated overnight at 37° C. and 5% CO2. Ala-6,12 human orexin-A as the agonist is prepared as a 1 mM stock solution in 1% bovine serum albumin (BSA) and diluted in assay buffer (HBSS containing 20 mM HEPES, 0.1% BSA and 2.5 mM probenecid, pH7.4) for use in the assay at a final concentration of 70 pM. Test compounds are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates, first in DMSO, then assay buffer. On the day of the assay, cells are washed 3 times with 100 ul assay buffer and then incubated for 60 min (37° C., 5% CO2) in 60 ul assay buffer containing 1 uM Fluo-4AM ester, 0.02% pluronic acid, and 1% BSA. The dye loading solution is then aspirated and cells are washed 3 times with 100 ul assay buffer. 30 ul of that same buffer is left in each well. Within the Fluorescent Imaging Plate Reader (FLIPR, Molecular Devices), test compounds are added to the plate in a volume of 25 ul, incubated for 5 min and finally 25 ul of agonist is added. Fluorescence is measured for each well at 1 second intervals for 5 minutes and the height of each fluorescence peak is compared to the height of the fluorescence peak induced by 70 pM Ala-6,12 orexin-A with buffer in place of antagonist.
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 399.45, ALogP 3.48, HBA 6, HBD 0, PSA 92, QED 0.67
Compound (SMILES): CCn1nc(C#Cc2cc(C(=O)Nc3ccc(CN4CCN(C)CC4)c(C(F)(F)F)c3)ccc2C)c2c(N)ncnc21
InChIKey: BNRXMSGHPVYSDK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of human Pim1
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 576.63, ALogP 4.16, HBA 8, HBD 2, PSA 105.2, QED 0.34
Compound (SMILES): C=CC(=O)N1CCC(n2nc(C#Cc3cc(C(=O)Nc4ccc(CN5CCN(C)CC5)c(C(F)(F)F)c4)ccc3C)c3c(N)ncnc32)CC1
InChIKey: VRCBGBBYFHLJRE-UHFFFAOYSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Kinase Inhibition Assays: The aim of this experiment is to detect the inhibitory activity of the compounds of the present invention against in vitro protein kinases using isotope labeling (labeled gamma phosphate groups on ATP). Kinase inhibition profiles were determined using KinaseProfiler services provided by Euro fins, and ATP concentrations used are the Km of corresponding kinases. In this study, we examined Abl (T315I) (h), ALK (h), ARK5 (h), Axl (h), Blk (h), Bmx (h), BTK (h), B-Raf (H), ckit (h), cSRC (h), CDK7, CHK1 (h), c-RAF (h), DDR2 (h), EGFR (h), EphA1 (h), EphA2 (h), EphA8 (h (H), FGF (h), Ft (h), Ft (h), F (h), F (h), Ft (h), Hb (h), ErbB2 (h), FAK (h) (H), JK3 (h), IKKalpha (h), IKKbeta (h), Itk (h), JAK3 (h), JNK11 (h), KDR (h), Lyn (h), MAPK1 (h), MEK1 (h (H), PKA (h), PKB [alpha](h), PKB [beta] (h), PKC [alpha] (h), Ret (H), RIPK2 (h), Src (1-530) (h), TAK1 (h), TBK1 (h), Tec (h) activated, Tie2 (h), TrkA (h), ULK3 (h) Yes (h), PI3 Kinase a (h) and other kinase in vitro inhibitory activity. The kinase inhibitory activity of the test compound is expressed as IC50 (half inhibitory concentration) or the inhibitory rate of the test compound at a concentration of 10 ??M for kinase activity. IC50 values can be obtained by calculating the inhibition rate of the kinase activity by the test compound at a series of different concentrations. The assay was as follows: In a reaction tube, the buffer (8 mM MOPS, pH 7.0, 0.2 mM EDTA, 10 mM MnCl2), the kinase to be tested (5-10 mU), the substrate to be tested kinase, 10 mM acetic acid Magnesium and gamma 33P-ATP solutions, as well as different concentrations of the test compound. MgATP was then added to the reaction to initiate the enzymatic reaction and incubated at room temperature for 40 minutes. The reaction was finally quenched with 5 ul of 3% phosphate buffer and 10 uL of the reaction solution was titrated onto a filtermat A membrane, washed three times with 75 mM phosphate solution for 5 minutes each, and washed again with methanol. Finally, the filtermat A film is dried and scintigraphized, and the size of the scintillation count reflects the degree to which the substrate is phosphorylated, thereby demonstrating that the kinase activity is inhibited. Among them, the percentage of the remaining active protein=the active protein of the experimental group the active protein of the control group 100%.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 685.75, ALogP 4.48, HBA 9, HBD 2, PSA 125.51, QED 0.22
Compound (SMILES): CC1(C)CCc2c(C(=O)Nc3cnn([C@H](c4ccccc4)C4CCS(=O)(=O)C4)c3)n[nH]c2C1
InChIKey: GQHAHPQLCBBLDS-IVAFLUGOSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin)
Measurement: Ki = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 467.6, ALogP 3.4, HBA 6, HBD 2, PSA 109.74, QED 0.6
Compound (SMILES): CC1(C)CCc2c(C(=O)Nc3cnn([C@H](c4ccccc4)C4CCCS(=O)(=O)C4)c3)n[nH]c2C1
InChIKey: VQAXOIUGIWGEFE-WBPHRXDCSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin)
Measurement: Ki = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 481.62, ALogP 3.79, HBA 6, HBD 2, PSA 109.74, QED 0.58
Compound (SMILES): CC1(C)CCc2c(C(=O)Nc3cnn([C@H](c4ccccc4)C4CCCCS4(=O)=O)c3)n[nH]c2C1
InChIKey: LLHYIISPPGQGTN-JFGZAKSSSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin)
Measurement: Ki > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 481.62, ALogP 3.93, HBA 6, HBD 2, PSA 109.74, QED 0.57
Compound (SMILES): CC1(C)CCc2c(C(=O)Nc3cnn([C@H](c4ccccc4)C4CC[S+]([O-])CC4)c3)n[nH]c2C1
InChIKey: TVHDLBOMEGOWNE-SINBQTRASA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin)
Measurement: Ki = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 465.62, ALogP 4.12, HBA 5, HBD 2, PSA 98.66, QED 0.55
Compound (SMILES): COc1ccc(-c2c(C)nn3c(NCCNC(C)=O)cc(C)nc23)cc1OC
InChIKey: FZPVOGSJCDLHJM-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)
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 383.45, ALogP 2.58, HBA 7, HBD 2, PSA 89.78, QED 0.61
Compound (SMILES): COc1ccc(-c2c(C)nn3c(NCCNC(=O)C(C)C)cc(C)nc23)cc1OC
InChIKey: DNJZVYYJYOBRHR-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)
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 411.51, ALogP 3.21, HBA 7, HBD 2, PSA 89.78, QED 0.55
Compound (SMILES): COc1ccc(-c2c(C)nn3c(NCCNS(C)(=O)=O)cc(C)nc23)cc1OC
InChIKey: KBKJZURSVLNLLH-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)
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 419.51, ALogP 1.99, HBA 8, HBD 2, PSA 106.85, QED 0.54
Compound (SMILES): COc1ccc(-c2c(C)nn3c(NCCOC(C)=O)cc(C)nc23)cc1OC
InChIKey: FKUYPWIYULBYKU-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)
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 384.44, ALogP 3.01, HBA 8, HBD 1, PSA 86.98, QED 0.49
Compound (SMILES): COc1ccc(-c2c(C)nc3c(NCCN4CCOCC4)ccnn23)cc1OC
InChIKey: CFLABOGUXKYRSK-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)
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 397.48, ALogP 2.47, HBA 8, HBD 1, PSA 73.15, QED 0.66
Compound (SMILES): COc1ccc(-c2c(C)nc3c(NCCNC(C)=O)cc(Cl)nn23)cc1OC
InChIKey: BENVEUQOMWIBNI-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)
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 403.87, ALogP 2.92, HBA 7, HBD 2, PSA 89.78, QED 0.59
Compound (SMILES): CC(=O)NCCNc1cc(Cl)nn2c(-c3ccc(F)c(C=O)c3)c(C)nc12
InChIKey: AHIAFMSFOPJWHU-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)
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 389.82, ALogP 2.86, HBA 6, HBD 2, PSA 88.39, QED 0.5
Compound (SMILES): CC(=O)NCCNc1cc(Cl)nn2c(-c3cccc(S(=O)(=O)NC(C)C)c3)c(C)nc12
InChIKey: GRXNKBNXVBDVRK-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)
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 464.98, ALogP 2.59, HBA 7, HBD 3, PSA 117.49, QED 0.44
Compound (SMILES): COc1ccc(-c2c(C)nc3c(NCCNC(C)=O)ccnn23)cc1OC
InChIKey: QEQHXLUUDIQJPT-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)
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 369.43, ALogP 2.27, HBA 7, HBD 2, PSA 89.78, QED 0.62
Compound (SMILES): COc1ccc(-c2c(C)nc3c(N)cc(Cl)nn23)cc1OC
InChIKey: QKMGMIGTYUUELE-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)
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 318.76, ALogP 2.96, HBA 6, HBD 1, PSA 74.67, QED 0.8
Compound (SMILES): C[C@H]1CNCCCN1S(=O)(=O)c1cccc2cncc(F)c12
InChIKey: QSKQVZWVLOIIEV-NSHDSACASA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 323.39, ALogP 1.75, HBA 4, HBD 1, PSA 62.3, QED 0.91
Compound (SMILES): CC(C)NCCCn1c(Sc2cc(Cl)cc(Cl)c2)nc2c(N)ncnc21
InChIKey: JYSLFQTWNRYWJT-UHFFFAOYSA-N
Target: Endoplasmin (SINGLE PROTEIN), Homo sapiens
UniProt: P14625
Assay: Binding affinity to Grp94 (unknown origin) by fluorescent polarization assay
Measurement: Kd = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 411.36, ALogP 4.25, HBA 7, HBD 2, PSA 81.65, QED 0.57
Compound (SMILES): COC(=O)c1c(O)cc(O)c(Cl)c1CCc1nccn1Cc1ccccc1
InChIKey: NCWIQXPFJORNJP-UHFFFAOYSA-N
Target: Endoplasmin (SINGLE PROTEIN), Homo sapiens
UniProt: P14625
Assay: Displacement of Cy3B-GM from recombinant Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 386.84, ALogP 3.57, HBA 6, HBD 2, PSA 84.58, QED 0.63
Compound (SMILES): Cc1ccccc1COc1ccc(C2C3=C(CC(C)(C)CC3=O)OC3=C2C(=O)CC(C)(C)C3)cc1
InChIKey: UEKIYVKPQNKSDI-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Positive allosteric modulation of human delta opioid receptor expressed in CHO cell membranes assessed as TAN67 Ki at 10 uM after 90 mins by [3H]-diprenorphine displacement assay (Rvb = 10 nM)
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 470.61, ALogP 6.97, HBA 4, HBD 0, PSA 52.6, QED 0.48
Compound (SMILES): O=C(CCCCSc1nc(-c2ccc(-c3ccccc3)cc2)cc(=O)[nH]1)NO
InChIKey: AOFVDNFTELWRHV-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of recombinant HDAC7 (unknown origin) by homogeneous fluorescence release assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 395.48, ALogP 3.87, HBA 5, HBD 3, PSA 95.08, QED 0.18
Compound (SMILES): O=C(/C=C/c1ccc(NC(=O)C(Cc2ccccc2)c2ccccc2)cn1)NO
InChIKey: UQSIPNLHOWORHA-BUHFOSPRSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of recombinant HDAC7 (unknown origin) by homogeneous fluorescence release assay
Measurement: IC50 = 8770 nM (pChEMBL 5.059999942779541)
Descriptors: MW 387.44, ALogP 3.57, HBA 4, HBD 3, PSA 91.32, QED 0.33
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc(Cl)c(NC[C@H]4CCCO4)n3)cc2)CC1
InChIKey: MMJSYUQCKWEFRW-QGZVFWFLSA-N
Target: Serine/threonine-protein kinase Chk1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14757
Assay: Inhibition of human CHK1 using KKKVSRSGLYRSPSMPENLNRPR peptide substrate by 33P Hotspot assay
Measurement: IC50 = 154 nM (pChEMBL 6.809999942779541)
Descriptors: MW 402.93, ALogP 3.22, HBA 7, HBD 2, PSA 65.55, QED 0.77
Compound (SMILES): O=C(CCCCCOc1no[n+]([O-])c1S(=O)(=O)c1ccccc1)NO
InChIKey: AGDGTFUFKSHWRN-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length human recombinant HDAC6 expressed in baculovirus infected insect S9 cells using Ac-Leu-GlyLys(Tfa)-AMC as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 371.37, ALogP 0.59, HBA 8, HBD 2, PSA 145.67, QED 0.28
Compound (SMILES): CCCCC(Oc1cc(O)c(C(=O)O)cc1C#Cc1ccccc1OC(F)(F)F)C(=O)NC1CCCCC1
InChIKey: DPPSTFALTNIFPF-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein phosphatase epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P23469
Assay: Inhibition of PTPepsilon (unknown origin) using pNPP as substrate at pH 7 at 25 degC by spectrophotometric analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 533.54, ALogP 5.78, HBA 5, HBD 3, PSA 105.09, QED 0.35
Compound (SMILES): [2H]C([2H])([2H])Oc1cc2nccc(Oc3ccc(NC(=O)Nc4cc(C)on4)c(Cl)c3)c2cc1OC([2H])([2H])[2H]
InChIKey: SPMVMDHWKHCIDT-XERRXZQWSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: Inhibition of recombinant VEGFR1 (unknown origin) by cell-free assay
Measurement: IC50 = 11.2 nM (pChEMBL 7.949999809265137)
Descriptors: MW 454.87, ALogP 5.64, HBA 7, HBD 2, PSA 107.74, QED 0.39
Compound (SMILES): CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](C[C@@H]1CCNC1=O)C(O)S(=O)(=O)[O-].[Na+]
InChIKey: BSPJDKCMFIPBAW-KVIMGBSASA-M
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS CoV 3CL protease using dabcyl-KTSAVLQ/SGFRKME-edans as substrate incubated for 30 mins followed by substrate addition measured after 30 mins by FRET assay
Measurement: IC50 = 4350 nM (pChEMBL 5.360000133514404)
Descriptors: MW 485.56, ALogP 0.54, HBA 7, HBD 5, PSA 171.13, QED 0.28
Compound (SMILES): COc1ccc(CNCCc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: DJIQHQYIPAYBKR-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 47.3 nM (pChEMBL 7.329999923706055)
Descriptors: MW 320.41, ALogP 1.67, HBA 4, HBD 2, PSA 81.42, QED 0.76
Compound (SMILES): CN(C)c1ccc(CNCCc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: GAFHFMSHSNKQDR-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 47.3 nM (pChEMBL 7.329999923706055)
Descriptors: MW 333.46, ALogP 1.73, HBA 4, HBD 2, PSA 75.43, QED 0.76
Compound (SMILES): CSC(=S)NS(=O)(=O)c1ccccc1
InChIKey: FEGLFSLWHIVPBO-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 pre-incubated for 8 hrs by stopped-flow CO2 hydration assay
Measurement: Ki = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 247.37, ALogP 1.61, HBA 4, HBD 1, PSA 46.17, QED 0.81
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2cccc(NC(C)=O)c2)n1
InChIKey: RHYMWMBUICSCMV-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR in human NCI-H460 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 17410 nM (pChEMBL 4.760000228881836)
Descriptors: MW 482.97, ALogP 4.38, HBA 8, HBD 2, PSA 91.85, QED 0.51
Compound (SMILES): CC(O)c1cc(=O)c(O)cn1-c1cccc(-c2ccccc2)c1
InChIKey: HDEBPDJWJHEWIK-UHFFFAOYSA-N
Target: Catechol O-methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P21964
Assay: Inhibition of recombinant human soluble COMT using dopamine/SAM as substrate/cofactor preincubated for 2 hrs followed by dopamine/SAM addition after 25 mins by fluorescence polarization assay
Measurement: IC50 = 940 nM (pChEMBL 6.03000020980835)
Descriptors: MW 307.35, ALogP 3.26, HBA 4, HBD 2, PSA 62.46, QED 0.78
Compound (SMILES): COc1cc(-c2cnc3c(N4CCOCC4)snc3c2)cc(OC)c1OC
InChIKey: JONPTLGCLPUHKH-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13163
Assay: Binding affinity to human MEK5
Measurement: Kd = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 387.46, ALogP 3.22, HBA 8, HBD 0, PSA 65.94, QED 0.67
Compound (SMILES): C[C@@H]1CC[C@@H](Oc2cc(C#N)ccn2)CN1C(=O)c1ccccc1-n1nccn1
InChIKey: FOEWIXNBXKVERV-NVXWUHKLSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Antagonist activity at human OX1R expressed in CHOK1 cells assessed as reduction in orexin A-induced calcium flux preincubated followed by orexin A addition by FLIPR assays
Measurement: IC50 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 388.43, ALogP 2.61, HBA 7, HBD 0, PSA 96.93, QED 0.68
Compound (SMILES): COC(=O)c1ccnc(O[C@@H]2CC[C@@H](C)N(C(=O)c3ccccc3-n3nccn3)C2)c1
InChIKey: YICJBMYJMAZRCL-NVXWUHKLSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: FLIPR Ca2+ Flux Assay: TBDIn a typical experiment the OX1 and OX2 receptor antagonistic activity of the compounds of the present invention was determined in accordance with the following experimental method. For intracellular calcium measurements, Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 g/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine. All reagents were from GIBCO-Invitrogen Corp. The seeded plates are incubated overnight at 37° C. and 5% CO2. Ala-6,12 human orexin-A as the agonist is prepared as a 1 mM stock solution in 1% bovine serum albumin (BSA) and diluted in assay buffer (HBSS containing 20 mM HEPES, 0.1% BSA and 2.5 mM probenecid, pH7.4) for use in the assay at a final concentration of 70 pM. Test compounds are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates, first in DMSO, then assay buffer. On the day of the assay, cells are washed 3 times with 100 μl assay buffer and then incubated for 60 min (37° C., 5% CO2) in 60 μl assay buffer containing 1 μM Fluo-4AM ester, 0.02% pluronic acid, and 1% BSA. The dye loading solution is then aspirated and cells are washed 3 times with 100 μl assay buffer. 30 μl of that same buffer is left in each well. Within the Fluorescent Imaging Plate Reader (FLIPR, Molecular Devices), test compounds are added to the plate in a volume of 25 μl, incubated for 5 min and finally 25 μl of agonist is added. Fluorescence is measured for each well at 1 second intervals for 5 minutes and the height of each fluorescence peak is compared to the height of the fluorescence peak induced by 70 pM Ala-6,12 orexin-A with buffer in place of antagonist.
Measurement: IC50 = 1402 nM (pChEMBL 5.849999904632568)
Descriptors: MW 421.46, ALogP 2.52, HBA 8, HBD 0, PSA 99.44, QED 0.58
Compound (SMILES): Cc1nc(-c2ccccc2C(=O)N2C[C@H](Oc3cc(C#N)ccn3)CC[C@H]2C)no1
InChIKey: DZHWCPHUSBPNJT-RHSMWYFYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56719
Assay: FLIPR Ca2+ Flux Assay: Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine. All reagents were from GIBCO-Invitrogen Corp. The seeded plates are incubated overnight at 37° C. and 5% CO2. Ala-6,12 human orexin-A as the agonist is prepared as a 1 mM stock solution in 1% bovine serum albumin (BSA) and diluted in assay buffer (HBSS containing 20 mM HEPES, 0.1% BSA and 2.5 mM probenecid, pH7.4) for use in the assay at a final concentration of 70 pM. Test compounds are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates, first in DMSO, then assay buffer. On the day of the assay, cells are washed 3 times with 100 ul assay buffer and then incubated for 60 min (37° C., 5% CO2) in 60 ul assay buffer containing 1 uM Fluo-4AM ester, 0.02% pluronic acid, and 1% BSA. The dye loading solution is then aspirated and cells are washed 3 times with 100 ul assay buffer. 30 ul of that same buffer is left in each well. Within the Fluorescent Imaging Plate Reader (FLIPR, Molecular Devices), test compounds are added to the plate in a volume of 25 ul, incubated for 5 min and finally 25 ul of agonist is added. Fluorescence is measured for each well at 1 second intervals for 5 minutes and the height of each fluorescence peak is compared to the height of the fluorescence peak induced by 70 pM Ala-6,12 orexin-A with buffer in place of antagonist.
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 403.44, ALogP 3.38, HBA 7, HBD 0, PSA 105.14, QED 0.66
Compound (SMILES): C[C@@H]1CC[C@@H](Oc2cc(C#N)ccn2)CN1C(=O)c1ccccc1-c1ncccn1
InChIKey: MMRBNOXAAQLWLU-SJLPKXTDSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: The inhibition constant (Ki) is determined using a radioligand binding assay (described in Bergman et. al. Bioorg. Med. Chem. Lett. 2008, 18, 1425-1430).
Measurement: Ki = 761 nM (pChEMBL 6.119999885559082)
Descriptors: MW 399.45, ALogP 3.48, HBA 6, HBD 0, PSA 92, QED 0.67
Compound (SMILES): CCn1nc(C#Cc2cc(C(=O)Nc3ccc(CN4CCN(C)CC4)c(C(F)(F)F)c3)ccc2C)c2c(N)ncnc21
InChIKey: BNRXMSGHPVYSDK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PAK 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13153
Assay: Inhibition of human PAK1
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 576.63, ALogP 4.16, HBA 8, HBD 2, PSA 105.2, QED 0.34
Compound (SMILES): CC1(C)CCc2c(C(=O)Nc3cnn([C@H](c4ccccc4)C4CCS(=O)(=O)C4)c3)n[nH]c2C1
InChIKey: GQHAHPQLCBBLDS-IVAFLUGOSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin)
Measurement: Ki = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 467.6, ALogP 3.4, HBA 6, HBD 2, PSA 109.74, QED 0.6
Compound (SMILES): CC1(C)CCc2c(C(=O)Nc3cnn([C@H](c4ccccc4)C4CCCS(=O)(=O)C4)c3)n[nH]c2C1
InChIKey: VQAXOIUGIWGEFE-WBPHRXDCSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin)
Measurement: Ki = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 481.62, ALogP 3.79, HBA 6, HBD 2, PSA 109.74, QED 0.58
Compound (SMILES): CC1(C)CCc2c(C(=O)Nc3cnn([C@H](c4ccccc4)C4CCCCS4(=O)=O)c3)n[nH]c2C1
InChIKey: LLHYIISPPGQGTN-JFGZAKSSSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin)
Measurement: Ki = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 481.62, ALogP 3.93, HBA 6, HBD 2, PSA 109.74, QED 0.57
Compound (SMILES): CC1(C)CCc2c(C(=O)Nc3cnn([C@H](c4ccccc4)C4CC[S+]([O-])CC4)c3)n[nH]c2C1
InChIKey: TVHDLBOMEGOWNE-SINBQTRASA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of LCK (unknown origin)
Measurement: Ki = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 465.62, ALogP 4.12, HBA 5, HBD 2, PSA 98.66, QED 0.55
Compound (SMILES): C[C@H]1CNCCCN1S(=O)(=O)c1cccc2cncc(F)c12
InChIKey: QSKQVZWVLOIIEV-NSHDSACASA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 323.39, ALogP 1.75, HBA 4, HBD 1, PSA 62.3, QED 0.91
Compound (SMILES): COC(=O)c1c(O)cc(O)c(Cl)c1CCc1nccn1Cc1ccccc1
InChIKey: NCWIQXPFJORNJP-UHFFFAOYSA-N
Target: Endoplasmin (SINGLE PROTEIN), Homo sapiens
UniProt: P14625
Assay: Displacement of FITC-GM from recombinant Grp94 (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: IC50 = 1150 nM (pChEMBL 5.940000057220459)
Descriptors: MW 386.84, ALogP 3.57, HBA 6, HBD 2, PSA 84.58, QED 0.63
Compound (SMILES): O=C(CCCCSc1nc(-c2ccc(-c3ccccc3)cc2)cc(=O)[nH]1)NO
InChIKey: AOFVDNFTELWRHV-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant HDAC6 (unknown origin) by homogeneous fluorescence release assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 395.48, ALogP 3.87, HBA 5, HBD 3, PSA 95.08, QED 0.18
Compound (SMILES): O=C(/C=C/c1ccc(NC(=O)C(Cc2ccccc2)c2ccccc2)cn1)NO
InChIKey: UQSIPNLHOWORHA-BUHFOSPRSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant HDAC6 (unknown origin) by homogeneous fluorescence release assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 387.44, ALogP 3.57, HBA 4, HBD 3, PSA 91.32, QED 0.33
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc(Cl)c(NC[C@H]4CCCO4)n3)cc2)CC1
InChIKey: MMJSYUQCKWEFRW-QGZVFWFLSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of human ALK using poly[Glu:Tyr] (4:1) peptide substrate by 33P Hotspot assay
Measurement: IC50 = 143 nM (pChEMBL 6.840000152587891)
Descriptors: MW 402.93, ALogP 3.22, HBA 7, HBD 2, PSA 65.55, QED 0.77
Compound (SMILES): O=C(CCCCCOc1no[n+]([O-])c1S(=O)(=O)c1ccccc1)NO
InChIKey: AGDGTFUFKSHWRN-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of full length human recombinant HDAC8 expressed in baculovirus infected insect S9 cells using Ac-Leu-GlyLys(Tfa)-AMC as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 343 nM (pChEMBL 6.460000038146973)
Descriptors: MW 371.37, ALogP 0.59, HBA 8, HBD 2, PSA 145.67, QED 0.28
Compound (SMILES): CCCCC(Oc1cc(O)c(C(=O)O)cc1C#Cc1ccccc1OC(F)(F)F)C(=O)NC1CCCCC1
InChIKey: DPPSTFALTNIFPF-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P35236
Assay: Inhibition of HePTP (unknown origin) using pNPP as substrate at pH 7 at 25 degC by spectrophotometric analysis
Measurement: IC50 = 8700 nM (pChEMBL 5.059999942779541)
Descriptors: MW 533.54, ALogP 5.78, HBA 5, HBD 3, PSA 105.09, QED 0.35
Compound (SMILES): CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](C[C@@H]1CCNC1=O)C(O)S(=O)(=O)[O-].[Na+]
InChIKey: BSPJDKCMFIPBAW-KVIMGBSASA-M
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Non-covalent inhibition of SARS-Cov-2 PLpro incubated for 30 mins using FRET substrate measured for 1 hr by FRET-based enzymatic assay
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 485.56, ALogP 0.54, HBA 7, HBD 5, PSA 171.13, QED 0.28
Compound (SMILES): COc1ccc(CNCCc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: DJIQHQYIPAYBKR-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human CA4 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 320.41, ALogP 1.67, HBA 4, HBD 2, PSA 81.42, QED 0.76
Compound (SMILES): CN(C)c1ccc(CNCCc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: GAFHFMSHSNKQDR-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human CA4 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 333.46, ALogP 1.73, HBA 4, HBD 2, PSA 75.43, QED 0.76
Compound (SMILES): CSC(=S)NS(=O)(=O)c1ccccc1
InChIKey: FEGLFSLWHIVPBO-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 pre-incubated for 6 hrs by stopped-flow CO2 hydration assay
Measurement: Ki = 55.93 nM (pChEMBL 7.25)
Descriptors: MW 247.37, ALogP 1.61, HBA 4, HBD 1, PSA 46.17, QED 0.81
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2cccc(NC(C)=O)c2)n1
InChIKey: RHYMWMBUICSCMV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 2910 nM (pChEMBL 5.539999961853027)
Descriptors: MW 482.97, ALogP 4.38, HBA 8, HBD 2, PSA 91.85, QED 0.51
Compound (SMILES): COc1cc(-c2cnc3c(N4CCOCC4)snc3c2)cc(OC)c1OC
InChIKey: JONPTLGCLPUHKH-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Binding affinity to human PDGFRalpha
Measurement: Kd = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 387.46, ALogP 3.22, HBA 8, HBD 0, PSA 65.94, QED 0.67
Compound (SMILES): C[C@@H]1CC[C@@H](Oc2cc(C#N)ccn2)CN1C(=O)c1ccccc1-n1nccn1
InChIKey: FOEWIXNBXKVERV-NVXWUHKLSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: The inhibition constant (Ki) is determined using a radioligand binding assay (described in Bergman et. al. Bioorg. Med. Chem. Lett. 2008, 18, 1425-1430).
Measurement: Ki = 813 nM (pChEMBL 6.090000152587891)
Descriptors: MW 388.43, ALogP 2.61, HBA 7, HBD 0, PSA 96.93, QED 0.68
Compound (SMILES): C[C@@H]1CC[C@@H](Oc2cc(C#N)ccn2)CN1C(=O)c1ccccc1-c1ncccn1
InChIKey: MMRBNOXAAQLWLU-SJLPKXTDSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: FLIPR Ca2+ Flux Assay: Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine. All reagents were from GIBCO-Invitrogen Corp. The seeded plates are incubated overnight at 37° C. and 5% CO2. Ala-6,12 human orexin-A as the agonist is prepared as a 1 mM stock solution in 1% bovine serum albumin (BSA) and diluted in assay buffer (HBSS containing 20 mM HEPES, 0.1% BSA and 2.5 mM probenecid, pH7.4) for use in the assay at a final concentration of 70 pM. Test compounds are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates, first in DMSO, then assay buffer. On the day of the assay, cells are washed 3 times with 100 ul assay buffer and then incubated for 60 min (37° C., 5% CO2) in 60 ul assay buffer containing 1 uM Fluo-4AM ester, 0.02% pluronic acid, and 1% BSA. The dye loading solution is then aspirated and cells are washed 3 times with 100 ul assay buffer. 30 ul of that same buffer is left in each well. Within the Fluorescent Imaging Plate Reader (FLIPR, Molecular Devices), test compounds are added to the plate in a volume of 25 ul, incubated for 5 min and finally 25 ul of agonist is added. Fluorescence is measured for each well at 1 second intervals for 5 minutes and the height of each fluorescence peak is compared to the height of the fluorescence peak induced by 70 pM Ala-6,12 orexin-A with buffer in place of antagonist.
Measurement: IC50 = 4868 nM (pChEMBL 5.309999942779541)
Descriptors: MW 399.45, ALogP 3.48, HBA 6, HBD 0, PSA 92, QED 0.67
Compound (SMILES): CCn1nc(C#Cc2cc(C(=O)Nc3ccc(CN4CCN(C)CC4)c(C(F)(F)F)c3)ccc2C)c2c(N)ncnc21
InChIKey: BNRXMSGHPVYSDK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of human mTOR
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 576.63, ALogP 4.16, HBA 8, HBD 2, PSA 105.2, QED 0.34
Compound (SMILES): C[C@H]1CNCCCN1S(=O)(=O)c1cccc2cncc(F)c12
InChIKey: QSKQVZWVLOIIEV-NSHDSACASA-N
Target: Tyrosine-protein kinase ABL2 (SINGLE PROTEIN), Homo sapiens
UniProt: P42684
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 323.39, ALogP 1.75, HBA 4, HBD 1, PSA 62.3, QED 0.91
Compound (SMILES): COC(=O)c1c(O)cc(O)c(Cl)c1CCc1nccn1Cc1ccccc1
InChIKey: NCWIQXPFJORNJP-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of FITC-geldanamycin from human HSP90alpha at 277 K after 5 hrs by fluorescence polarization assay
Measurement: Ki = 1800 nM (pChEMBL 5.75)
Descriptors: MW 386.84, ALogP 3.57, HBA 6, HBD 2, PSA 84.58, QED 0.63
Compound (SMILES): O=C(CCCCSc1nc(-c2ccc(-c3ccccc3)cc2)cc(=O)[nH]1)NO
InChIKey: AOFVDNFTELWRHV-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant HDAC5 (unknown origin) by homogeneous fluorescence release assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 395.48, ALogP 3.87, HBA 5, HBD 3, PSA 95.08, QED 0.18
Compound (SMILES): O=C(/C=C/c1ccc(NC(=O)C(Cc2ccccc2)c2ccccc2)cn1)NO
InChIKey: UQSIPNLHOWORHA-BUHFOSPRSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant HDAC5 (unknown origin) by homogeneous fluorescence release assay
Measurement: IC50 = 9370 nM (pChEMBL 5.03000020980835)
Descriptors: MW 387.44, ALogP 3.57, HBA 4, HBD 3, PSA 91.32, QED 0.33
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc(Cl)c(NC[C@H]4CCCO4)n3)cc2)CC1
InChIKey: MMJSYUQCKWEFRW-QGZVFWFLSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of human LCK using peptide poly[Glu:Tyr] (4:1) substrate by 33P Hotspot assay
Measurement: IC50 = 136 nM (pChEMBL 6.869999885559082)
Descriptors: MW 402.93, ALogP 3.22, HBA 7, HBD 2, PSA 65.55, QED 0.77
Compound (SMILES): O=C(CCCCCOc1no[n+]([O-])c1S(=O)(=O)c1ccccc1)NO
InChIKey: AGDGTFUFKSHWRN-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of full length human recombinant HDAC11 expressed in baculovirus infected insect S9 cells after 30 mins by fluorescence assay
Measurement: IC50 = 608 nM (pChEMBL 6.21999979019165)
Descriptors: MW 371.37, ALogP 0.59, HBA 8, HBD 2, PSA 145.67, QED 0.28
Compound (SMILES): CCCCC(Oc1cc(O)c(C(=O)O)cc1C#Cc1ccccc1OC(F)(F)F)C(=O)NC1CCCCC1
InChIKey: DPPSTFALTNIFPF-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of SHP2 (unknown origin) using pNPP as substrate at pH 7 at 25 degC by spectrophotometric analysis
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 533.54, ALogP 5.78, HBA 5, HBD 3, PSA 105.09, QED 0.35
Compound (SMILES): CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](C[C@@H]1CCNC1=O)C(O)S(=O)(=O)[O-].[Na+]
InChIKey: BSPJDKCMFIPBAW-KVIMGBSASA-M
Target: Calpain-1 catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P07384
Assay: Covalent inhibition of Calpain 1 (unknown origin) incubated for 1 hr by FRET-based enzymatic assay
Measurement: IC50 <= 74 nM (pChEMBL 7.13100004196167)
Descriptors: MW 485.56, ALogP 0.54, HBA 7, HBD 5, PSA 171.13, QED 0.28
Compound (SMILES): COc1ccc(CNCCc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: DJIQHQYIPAYBKR-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 45.3 nM (pChEMBL 7.340000152587891)
Descriptors: MW 320.41, ALogP 1.67, HBA 4, HBD 2, PSA 81.42, QED 0.76
Compound (SMILES): CN(C)c1ccc(CNCCc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: GAFHFMSHSNKQDR-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 45.3 nM (pChEMBL 7.340000152587891)
Descriptors: MW 333.46, ALogP 1.73, HBA 4, HBD 2, PSA 75.43, QED 0.76
Compound (SMILES): CSC(=S)NS(=O)(=O)c1ccccc1
InChIKey: FEGLFSLWHIVPBO-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 pre-incubated for 4 hrs by stopped-flow CO2 hydration assay
Measurement: Ki = 60.21 nM (pChEMBL 7.21999979019165)
Descriptors: MW 247.37, ALogP 1.61, HBA 4, HBD 1, PSA 46.17, QED 0.81
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2cccc(NC(C)=O)c2)n1
InChIKey: RHYMWMBUICSCMV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of ABL T315I mutant in mouse BAF3 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 5560 nM (pChEMBL 5.25)
Descriptors: MW 482.97, ALogP 4.38, HBA 8, HBD 2, PSA 91.85, QED 0.51
Compound (SMILES): COc1cc(-c2cnc3c(N4CCOCC4)snc3c2)cc(OC)c1OC
InChIKey: JONPTLGCLPUHKH-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Binding affinity to human PDGFRbeta
Measurement: Kd = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 387.46, ALogP 3.22, HBA 8, HBD 0, PSA 65.94, QED 0.67
Compound (SMILES): C[C@@H]1CC[C@@H](Oc2cc(C#N)ccn2)CN1C(=O)c1ccccc1-n1nccn1
InChIKey: FOEWIXNBXKVERV-NVXWUHKLSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56719
Assay: FLIPR Ca2+ Flux Assay: Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine. All reagents were from GIBCO-Invitrogen Corp. The seeded plates are incubated overnight at 37° C. and 5% CO2. Ala-6,12 human orexin-A as the agonist is prepared as a 1 mM stock solution in 1% bovine serum albumin (BSA) and diluted in assay buffer (HBSS containing 20 mM HEPES, 0.1% BSA and 2.5 mM probenecid, pH7.4) for use in the assay at a final concentration of 70 pM. Test compounds are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates, first in DMSO, then assay buffer. On the day of the assay, cells are washed 3 times with 100 ul assay buffer and then incubated for 60 min (37° C., 5% CO2) in 60 ul assay buffer containing 1 uM Fluo-4AM ester, 0.02% pluronic acid, and 1% BSA. The dye loading solution is then aspirated and cells are washed 3 times with 100 ul assay buffer. 30 ul of that same buffer is left in each well. Within the Fluorescent Imaging Plate Reader (FLIPR, Molecular Devices), test compounds are added to the plate in a volume of 25 ul, incubated for 5 min and finally 25 ul of agonist is added. Fluorescence is measured for each well at 1 second intervals for 5 minutes and the height of each fluorescence peak is compared to the height of the fluorescence peak induced by 70 pM Ala-6,12 orexin-A with buffer in place of antagonist.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 388.43, ALogP 2.61, HBA 7, HBD 0, PSA 96.93, QED 0.68
Compound (SMILES): CCn1nc(C#Cc2cc(C(=O)Nc3ccc(CN4CCN(C)CC4)c(C(F)(F)F)c3)ccc2C)c2c(N)ncnc21
InChIKey: BNRXMSGHPVYSDK-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q02750
Assay: Inhibition of human MEK1
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 576.63, ALogP 4.16, HBA 8, HBD 2, PSA 105.2, QED 0.34
Compound (SMILES): C[C@H]1CNCCCN1S(=O)(=O)c1cccc2cncc(F)c12
InChIKey: QSKQVZWVLOIIEV-NSHDSACASA-N
Target: Acyl-CoA dehydrogenase family member 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6JQN1
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 323.39, ALogP 1.75, HBA 4, HBD 1, PSA 62.3, QED 0.91
Compound (SMILES): COC(=O)c1c(O)cc(O)c(Cl)c1CCc1nccn1Cc1ccccc1
InChIKey: NCWIQXPFJORNJP-UHFFFAOYSA-N
Target: Endoplasmin (SINGLE PROTEIN), Canis lupus familiaris
UniProt: P41148
Assay: Displacement of FITC-geldanamycin from full length dog GRP94 at 277 K after 5 hrs by fluorescence polarization assay
Measurement: Ki = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 386.84, ALogP 3.57, HBA 6, HBD 2, PSA 84.58, QED 0.63
Compound (SMILES): O=C(CCCCSc1nc(-c2ccc(-c3ccccc3)cc2)cc(=O)[nH]1)NO
InChIKey: AOFVDNFTELWRHV-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant HDAC4 (unknown origin) by homogeneous fluorescence release assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 395.48, ALogP 3.87, HBA 5, HBD 3, PSA 95.08, QED 0.18
Compound (SMILES): O=C(/C=C/c1ccc(NC(=O)C(Cc2ccccc2)c2ccccc2)cn1)NO
InChIKey: UQSIPNLHOWORHA-BUHFOSPRSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant HDAC4 (unknown origin) by homogeneous fluorescence release assay
Measurement: IC50 = 11700 nM (pChEMBL 4.929999828338623)
Descriptors: MW 387.44, ALogP 3.57, HBA 4, HBD 3, PSA 91.32, QED 0.33
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc(Cl)c(NC[C@H]4CCCO4)n3)cc2)CC1
InChIKey: MMJSYUQCKWEFRW-QGZVFWFLSA-N
Target: Proto-oncogene tyrosine-protein kinase ROS (SINGLE PROTEIN), Homo sapiens
UniProt: P08922
Assay: Inhibition of human ROS/ROS1 using KKKSPGEYVNIEFG peptide substrate by 33P Hotspot assay
Measurement: IC50 = 124 nM (pChEMBL 6.909999847412109)
Descriptors: MW 402.93, ALogP 3.22, HBA 7, HBD 2, PSA 65.55, QED 0.77
Compound (SMILES): O=C(CCCCCOc1no[n+]([O-])c1S(=O)(=O)c1ccccc1)NO
InChIKey: AGDGTFUFKSHWRN-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 38000 nM (pChEMBL 4.420000076293945)
Descriptors: MW 371.37, ALogP 0.59, HBA 8, HBD 2, PSA 145.67, QED 0.28
Compound (SMILES): CCCCC(Oc1cc(O)c(C(=O)O)cc1C#Cc1ccccc1OC(F)(F)F)C(=O)NC1CCCCC1
InChIKey: DPPSTFALTNIFPF-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P29350
Assay: Inhibition of SHP1 (unknown origin) using pNPP as substrate at pH 7 at 25 degC by spectrophotometric analysis
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 533.54, ALogP 5.78, HBA 5, HBD 3, PSA 105.09, QED 0.35
Compound (SMILES): CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](C[C@@H]1CCNC1=O)C(O)S(=O)(=O)[O-].[Na+]
InChIKey: BSPJDKCMFIPBAW-KVIMGBSASA-M
Target: Cathepsin K (SINGLE PROTEIN), Homo sapiens
UniProt: P43235
Assay: Covalent inhibition of Cathepsin K (unknown origin) incubated for 30 mins using FRET substrate measured for 1 hr by FRET-based enzymatic assay
Measurement: IC50 <= 74 nM (pChEMBL 7.13100004196167)
Descriptors: MW 485.56, ALogP 0.54, HBA 7, HBD 5, PSA 171.13, QED 0.28
Compound (SMILES): COc1ccc(CNCCc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: DJIQHQYIPAYBKR-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA12 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 46.2 nM (pChEMBL 7.329999923706055)
Descriptors: MW 320.41, ALogP 1.67, HBA 4, HBD 2, PSA 81.42, QED 0.76
Compound (SMILES): CN(C)c1ccc(CNCCc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: GAFHFMSHSNKQDR-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA12 pre-incubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 46.2 nM (pChEMBL 7.329999923706055)
Descriptors: MW 333.46, ALogP 1.73, HBA 4, HBD 2, PSA 75.43, QED 0.76
Compound (SMILES): CSC(=S)NS(=O)(=O)c1ccccc1
InChIKey: FEGLFSLWHIVPBO-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 pre-incubated for 2 hrs by stopped-flow CO2 hydration assay
Measurement: Ki = 62.73 nM (pChEMBL 7.199999809265137)
Descriptors: MW 247.37, ALogP 1.61, HBA 4, HBD 1, PSA 46.17, QED 0.81
Compound (SMILES): COc1cc(-c2cnc3c(N4CCOCC4)snc3c2)cc(OC)c1OC
InChIKey: JONPTLGCLPUHKH-UHFFFAOYSA-N
Target: Cyclin-G-associated kinase (SINGLE PROTEIN), Homo sapiens
UniProt: O14976
Assay: Binding affinity to GAK (unknown origin)
Measurement: Kd = 8.9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 387.46, ALogP 3.22, HBA 8, HBD 0, PSA 65.94, QED 0.67
Compound (SMILES): CCn1nc(C#Cc2cc(C(=O)Nc3ccc(CN4CCN(C)CC4)c(C(F)(F)F)c3)ccc2C)c2c(N)ncnc21
InChIKey: BNRXMSGHPVYSDK-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of human MAPK1
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 576.63, ALogP 4.16, HBA 8, HBD 2, PSA 105.2, QED 0.34
Compound (SMILES): C[C@H]1CNCCCN1S(=O)(=O)c1cccc2cncc(F)c12
InChIKey: QSKQVZWVLOIIEV-NSHDSACASA-N
Target: Acyl-CoA dehydrogenase family member 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q709F0
Assay: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.
Measurement: Kd > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 323.39, ALogP 1.75, HBA 4, HBD 1, PSA 62.3, QED 0.91
Compound (SMILES): COC(=O)c1c(O)cc(O)c(Cl)c1CCc1nccn1Cc1ccccc1
InChIKey: NCWIQXPFJORNJP-UHFFFAOYSA-N
Target: Endoplasmin (SINGLE PROTEIN), Canis lupus familiaris
UniProt: P41148
Assay: Displacement of FITC-geldanamycin from full length dog GRP94 at 277 K after 5 hrs by fluorescence polarization assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 386.84, ALogP 3.57, HBA 6, HBD 2, PSA 84.58, QED 0.63