lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1C(=O)C(c2ccsc2)(c2cccc(-c3cnccn3)c2)N=C1N
InChIKey: NXXHXFSKVSTXAG-UHFFFAOYSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of cathepsin D by FRET assay
Measurement: IC50 = 33000 nM (pChEMBL 4.480000019073486)
Descriptors: MW 349.42, ALogP 2.24, HBA 6, HBD 1, PSA 84.47, QED 0.79
Compound (SMILES): CCC(=O)c1cc(C2(c3cccc(-c4cccnc4F)c3)N=C(N)N(C)C2=O)cs1
InChIKey: SYHWIMVHWVXBDN-UHFFFAOYSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of cathepsin D by FRET assay
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 422.49, ALogP 3.57, HBA 6, HBD 1, PSA 88.65, QED 0.5
Compound (SMILES): CCC(=O)c1cc([C@]2(c3cccc(-c4cccnc4F)c3)N=C(N)N(C)C2=O)cs1
InChIKey: SYHWIMVHWVXBDN-QFIPXVFZSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of cathepsin D by FRET assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 422.49, ALogP 3.57, HBA 6, HBD 1, PSA 88.65, QED 0.5
Compound (SMILES): Cc1cccc(-c2[nH]c(C(C)(C)C)nc2-c2ccc3c(c2)OCO3)n1.Cl
InChIKey: BTUOOXPZOVNPMF-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of GST tagged TbetaR-1 (unknown origin) by Westernblot assay
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 335.41, ALogP 4.47, HBA 4, HBD 1, PSA 60.03, QED 0.75
Compound (SMILES): Cl.O=C(N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1ccnc(Cl)c1
InChIKey: RMCXSXUPSMUNGA-NHHGTILHSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity against mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]-GTPgammaS binding
Measurement: EC50 = 0.83 nM (pChEMBL 9.079999923706055)
Descriptors: MW 481.98, ALogP 2.8, HBA 6, HBD 3, PSA 94.92, QED 0.58
Compound (SMILES): Cl.O=C(N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1ccnc(Br)c1
InChIKey: LIODVMHGQVYESL-NHHGTILHSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity against mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]-GTPgammaS binding
Measurement: EC50 = 1.19 nM (pChEMBL 8.920000076293945)
Descriptors: MW 526.43, ALogP 2.91, HBA 6, HBD 3, PSA 94.92, QED 0.53
Compound (SMILES): Cl.O=C(CCc1ccncc1)N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5
InChIKey: XWCRBEYCIKMNSO-JIMVDJGHSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity against mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]-GTPgammaS binding
Measurement: EC50 = 1.46 nM (pChEMBL 8.84000015258789)
Descriptors: MW 475.59, ALogP 2.47, HBA 6, HBD 3, PSA 94.92, QED 0.59
Compound (SMILES): Cc1cc(C(=O)N[C@@H]2CC[C@@]3(O)[C@H]4Cc5ccc(O)c6c5[C@@]3(CCN4CC3CC3)[C@H]2O6)ccn1.Cl
InChIKey: DWPNKFGOPCMQPA-APVPXXETSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity against mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]-GTPgammaS binding
Measurement: EC50 = 1.13 nM (pChEMBL 8.949999809265137)
Descriptors: MW 461.56, ALogP 2.46, HBA 6, HBD 3, PSA 94.92, QED 0.65
Compound (SMILES): Cl.O=C(N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1ccncc1Br
InChIKey: YNKHKFRVSKZOFC-IQELHQNUSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity against mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]-GTPgammaS binding
Measurement: EC50 = 1.31 nM (pChEMBL 8.880000114440918)
Descriptors: MW 526.43, ALogP 2.91, HBA 6, HBD 3, PSA 94.92, QED 0.57
Compound (SMILES): Cl.O=C(N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1ccncc1Cl
InChIKey: OUYHOJRQDCJGKJ-IQELHQNUSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity against mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]-GTPgammaS binding
Measurement: EC50 = 2.32 nM (pChEMBL 8.630000114440918)
Descriptors: MW 481.98, ALogP 2.8, HBA 6, HBD 3, PSA 94.92, QED 0.62
Compound (SMILES): Cc1cnccc1C(=O)N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5.Cl
InChIKey: GVQOZXIRFMKSTJ-APVPXXETSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity against mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]-GTPgammaS binding
Measurement: EC50 = 1.52 nM (pChEMBL 8.819999694824219)
Descriptors: MW 461.56, ALogP 2.46, HBA 6, HBD 3, PSA 94.92, QED 0.65
Compound (SMILES): Cl.O=C(Cc1ccncc1)N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5
InChIKey: MKBMLMVJNQPFKC-NCFDXLCNSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity against mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]-GTPgammaS binding
Measurement: EC50 = 2.32 nM (pChEMBL 8.630000114440918)
Descriptors: MW 461.56, ALogP 2.08, HBA 6, HBD 3, PSA 94.92, QED 0.63
Compound (SMILES): Cl.O=C(CNC(=O)c1ccncc1)N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5
InChIKey: GEUBDVMAWKJQAB-QTJUMRCSSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity against mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]-GTPgammaS binding
Measurement: EC50 = 2.84 nM (pChEMBL 8.550000190734863)
Descriptors: MW 504.59, ALogP 1.27, HBA 7, HBD 4, PSA 124.02, QED 0.47
Compound (SMILES): CN1CCC(C(=O)N[C@@H]2CC[C@@]3(O)[C@H]4Cc5ccc(O)c6c5[C@@]3(CCN4CC3CC3)[C@H]2O6)CC1.Cl
InChIKey: BEMLTQBXQXGYNK-APVPXXETSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity against mu opioid receptor expressed in CHO cells assessed as stimulation of [35S]-GTPgammaS binding
Measurement: EC50 = 5.08 nM (pChEMBL 8.289999961853027)
Descriptors: MW 467.61, ALogP 1.78, HBA 6, HBD 3, PSA 85.27, QED 0.63
Compound (SMILES): Cl.OC12CC3CC(CC(C3)N1Cc1ccccc1)C2
InChIKey: ZHHLHBNBIKLLJG-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Inhibition of kappa opioid receptor by NIMH PDSP
Measurement: Ki = 662.4 nM (pChEMBL 6.179999828338623)
Descriptors: MW 243.35, ALogP 2.77, HBA 2, HBD 1, PSA 23.47, QED 0.86
Compound (SMILES): Cl.OC12CC3CC(CC(C3)N1Cc1cccc(F)c1)C2
InChIKey: LPAMOYXJLQSGRI-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Inhibition of H1 receptor by NIMH PDSP
Measurement: Ki < 10000 nM (pChEMBL 5)
Descriptors: MW 261.34, ALogP 2.91, HBA 2, HBD 1, PSA 23.47, QED 0.88
Compound (SMILES): Cl.c1ccc(CN2C3CC4CC(C3)CC2C4)cc1
InChIKey: HXOMGUPFBWZKBK-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Inhibition of M5 muscarinic receptor by NIMH PDSP
Measurement: Ki = 6546 nM (pChEMBL 5.179999828338623)
Descriptors: MW 227.35, ALogP 3.45, HBA 1, HBD 0, PSA 3.24, QED 0.75
Compound (SMILES): Cl.Fc1cccc(CN2C3CC4CC(C3)CC2C4)c1
InChIKey: ZILQWXOKQUVSTI-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Inhibition of M2 muscarinic receptor by NIMH PDSP
Measurement: Ki = 3542 nM (pChEMBL 5.449999809265137)
Descriptors: MW 245.34, ALogP 3.59, HBA 1, HBD 0, PSA 3.24, QED 0.77
Compound (SMILES): CS(=O)(=O)N(CCN1CCOCC1)c1ccc(Nc2ncc3cnn(C4CCCCCC4)c3n2)cc1
InChIKey: XFWNXRYYGPIPLI-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 using a fluorescent probe 7-benzyloxy-4(trifluoromethyl)-coumarin
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 513.67, ALogP 3.56, HBA 9, HBD 1, PSA 105.48, QED 0.46
Compound (SMILES): CS(=O)(=O)Nc1ccc(Nc2ncc3cnn(C4CCCCCC4)c3n2)cn1
InChIKey: PARUULGUCQEWNM-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 401.5, ALogP 3.23, HBA 8, HBD 2, PSA 114.69, QED 0.63
Compound (SMILES): CC(Oc1cc(-c2cnn(C3CCNCC3)c2)cnc1N)c1c(Cl)ccc(F)c1Cl
InChIKey: KTEIFNKAUNYNJU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase MRCK alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VT25
Assay: PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: CDC42BPA
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 450.35, ALogP 5.04, HBA 6, HBD 2, PSA 77.99, QED 0.53
Compound (SMILES): C[C@H](Oc1cc(-c2cnn(C3CCNCC3)c2)cnc1N)c1c(Cl)ccc(F)c1Cl
InChIKey: KTEIFNKAUNYNJU-LBPRGKRZSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Binding affinity to MET (unknown origin)
Measurement: Kd = 37.5 nM (pChEMBL 7.429999828338623)
Descriptors: MW 450.35, ALogP 5.04, HBA 6, HBD 2, PSA 77.99, QED 0.53
Compound (SMILES): Cc1ccc(C(=O)NC2CC2)cc1-c1ccc2c(c1)NC(=O)C21CCOCC1
InChIKey: BKDNDBILDOURLT-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition Assay: Enzymatic activity assay was performed in 96-well microtiter plates (Corning, catalog number #3686) using a total volume of 50 ul of an assay buffer composed of 50 mM HEPES pH 7.5, 10 mM MgCl2, 1.75 mM Na3VO4. Various concentrations of the test compound or vehicle controls were pre-incubated for one hour with 0.055 ug/ml of the human p38alfa (SAPKa) enzyme (obtained from University of Dundee). The reaction was started by addition of biotinylated ATF2 substrate and ATP in concentrations around their Km values (final concentration 0.62 uM and 60 uM respectively) and took place for one hour at 25 C. Addition of the detection reagents, streptavidin XL665 and anti-phosphoresidue antibody coupled to Europium cryptate, caused the juxtaposition of the cryptate and the XL665 fluorophore, resulting in fluorescence energy transfer (FRET). The FRET intensity depends on the amount of bounded cryptate antibody, which is proportional to the extent of substrate phosphorylation.
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 376.46, ALogP 3.55, HBA 3, HBD 2, PSA 67.43, QED 0.86
Compound (SMILES): CCCCCn1cc(C(=O)Nc2cccc3ccccc23)c2ccccc21
InChIKey: GWCQNKRMTGVYIZ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor expressed in CHO cells assessed as increase of forskolin-stimulated cAMP accumulation after 20 mins
Measurement: EC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 356.47, ALogP 6.24, HBA 2, HBD 1, PSA 34.03, QED 0.41
Compound (SMILES): CCCCCn1cc(C(=O)Nc2ccc3ccccc3c2)c2ccccc21
InChIKey: LKGPFICOQRIBQC-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor expressed in CHO cells assessed as increase of forskolin-stimulated cAMP accumulation after 20 mins
Measurement: EC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 356.47, ALogP 6.24, HBA 2, HBD 1, PSA 34.03, QED 0.41
Compound (SMILES): CCCCCn1cc(C(=O)c2cccc3ccccc23)c2cccnc21
InChIKey: IMGJLJWXTHYHIG-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor expressed in CHO cells assessed as increase of forskolin-stimulated cAMP accumulation after 20 mins
Measurement: EC50 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 342.44, ALogP 5.61, HBA 3, HBD 0, PSA 34.89, QED 0.34
Compound (SMILES): COCCn1cc(C(=O)c2cccc3ccccc23)c2cccnc21
InChIKey: DXGSMGNKLUGXSZ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor expressed in CHO cells assessed as increase of forskolin-stimulated cAMP accumulation after 20 mins
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 330.39, ALogP 4.07, HBA 4, HBD 0, PSA 44.12, QED 0.52
Compound (SMILES): Cc1noc(C)c1-c1ccc2c(c1)CN(C)C(=O)N2
InChIKey: DRKGLYHLBGWKHL-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of first bromodomain of BRD4
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 257.29, ALogP 2.94, HBA 3, HBD 1, PSA 58.37, QED 0.85
Compound (SMILES): Cc1noc(C)c1-c1ccccc1
InChIKey: BHAXDAUULXCVEK-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human His-tagged bromodomain BRD4(1) by isothermal titration calorimetry
Measurement: Kd = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 173.21, ALogP 2.96, HBA 2, HBD 0, PSA 26.03, QED 0.66
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2cccc(-c3ccc(C(F)(F)F)cc3)c2)cc1
InChIKey: ZOPNBMMVVZRSGH-NRFANRHFSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Partial agonist activity at human GPR40 expressed in CHO cells measured over 20 secs interval by luminometric analysis in presence of 0.01% human serum albumin
Measurement: EC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 438.45, ALogP 6.53, HBA 2, HBD 1, PSA 46.53, QED 0.43
Compound (SMILES): Cc1cc(OCCCS(C)(=O)=O)cc(C)c1-c1cccc(COc2ccc3c(c2)OC[C@H]3CC(=O)O)c1
InChIKey: BZCALJIHZVNMGJ-HSZRJFAPSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human FFAR1 expressed in CHO cells assessed as increase in intracellular calcium level by Fluo 4-AM dye-based FLIPR assay
Measurement: EC50 = 33.6 nM (pChEMBL 7.46999979019165)
Descriptors: MW 524.64, ALogP 5.31, HBA 6, HBD 1, PSA 99.13, QED 0.34
Compound (SMILES): COc1cc2c(NC3CCN(C4CCCCC4)CC3)nc(N3CCCN(C(C)C)CC3)nc2cc1OCCCN1CCCCC1
InChIKey: OUKWLRHRXOPODD-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of G9a in human PC3 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 621.91, ALogP 6.02, HBA 9, HBD 1, PSA 69.23, QED 0.3
Compound (SMILES): COc1cc2c(NC3CCN(CC4CCCCC4)CC3)nc(N3CCCN(C(C)C)CC3)nc2cc1OCCCN1CCCCC1
InChIKey: XFAXSWXKPQWHDW-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of G9a in human PC3 cells assessed as reduction of H3K9me2 after 48 hrs by In-Cell Western assay
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 635.94, ALogP 6.27, HBA 9, HBD 1, PSA 69.23, QED 0.27
Compound (SMILES): C[C@@H]1CCCN1CCCOc1ccc(-c2ccc(=O)[nH]n2)cc1
InChIKey: XUKROCVZGZNGSI-CQSZACIVSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYN8
Assay: Antagonist activity at histamine H3 receptor in rat cortical membrane
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 313.4, ALogP 2.69, HBA 4, HBD 1, PSA 58.22, QED 0.83
Compound (SMILES): C[C@H](N)C(=O)NCC(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: NHXLMOGPVYXJNR-ZPHDWPCDSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst5 receptor in HEK293 cells after 2 hrs by autoradiography
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 1637.91
Compound (SMILES): CCCCCCCCCC(=O)CC(=O)N[C@H]1CCSC1=O
InChIKey: DTKPMZLHSRTKNJ-AWEZNQCLSA-N
Target: PhzR (SINGLE PROTEIN), Pseudomonas aeruginosa
UniProt: Q9RMS5
Assay: Agonist activity at Pseudomonas aeruginosa QscR expressed in Escherichia coli JLD271 harboring QscR expression plasmid pJN105Q and pPA1897-lacZ transcriptional fusion reporter pSC11-Q measured after 35 mins by Miller-type beta-galactosidase reporter gene assay
Measurement: EC50 = 80.46 nM (pChEMBL 7.090000152587891)
Descriptors: MW 313.46, ALogP 3.23, HBA 4, HBD 1, PSA 63.24, QED 0.47
Compound (SMILES): C[C@H](N)C(=O)NCC(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: QIXXUKXLULSIND-REMOFRLVSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst5 receptor in HEK293 cells after 2 hrs by autoradiography
Measurement: IC50 = 556 nM (pChEMBL 6.25)
Descriptors: MW 1614.87
Compound (SMILES): C[C@H](N)C(=O)NCC(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: QIXXUKXLULSIND-TTZRXDBLSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst5 receptor in HEK293 cells after 2 hrs by autoradiography
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 1614.87
Compound (SMILES): C[C@H](N)C(=O)NCC(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: PPMRXEMNCQTEFU-DQMVLKBGSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst5 receptor in HEK293 cells after 2 hrs by autoradiography
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 1648.93
Compound (SMILES): C[C@H](N)C(=O)NCC(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: PPMRXEMNCQTEFU-RPZSHQLJSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst5 receptor in HEK293 cells after 2 hrs by autoradiography
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 1648.93
Compound (SMILES): C[C@H](N)C(=O)NCC(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2cn(Cc3ccccc3)cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: PCOKLAQIKLJNCC-TUQJLTHMSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst5 receptor in HEK293 cells after 2 hrs by autoradiography
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1678.96
Compound (SMILES): C[C@H](N)C(=O)NCC(=O)N[C@H]1CSSC[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2cn(Cc3ccccc3)cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC1=O
InChIKey: PCOKLAQIKLJNCC-PPQOTRBLSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst5 receptor in HEK293 cells after 2 hrs by autoradiography
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1678.96
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](N)CSSC[C@@H](C(=O)O)NC(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: PJRZZHKHLDKTKL-VJLATZRLSA-N
Target: Somatostatin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30872
Assay: Binding affinity towards human somatostatin receptor type 1 using [125I][Leu8,D-Trp22,Tyr25]SRIF-28 as radioligand.
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 1079.32
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2ccc3ccccc3c2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](N)CSSC[C@@H](C(=O)O)NC(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: ZWDCQOWLWNRGRH-LWNGEPAASA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst5 receptor in HEK293 cells after 2 hrs by autoradiography
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 1090.34
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2cn(Cc3ccccc3)cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](N)CSSC[C@@H](C(=O)O)NC(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: QGPLCSNQORHDTQ-UVDDJNJYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst5 receptor in HEK293 cells after 2 hrs by autoradiography
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1120.37
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc2cn(Cc3ccccc3)cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](N)CSSC[C@@H](C(=O)O)NC(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: QGPLCSNQORHDTQ-VQFDOSOCSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P35346
Assay: Displacement of 125I-[LTT]-SRIF-28 from human sst5 receptor in HEK293 cells after 2 hrs by autoradiography
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 1120.37
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OC
InChIKey: FJUMAPNPNSYMAU-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 463.49, ALogP 5.37, HBA 8, HBD 2, PSA 120.63, QED 0.39
Compound (SMILES): COc1cc2ncnc(Sc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OC
InChIKey: FFLVHWGDEYLFKE-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 479.56, ALogP 5.73, HBA 8, HBD 2, PSA 111.4, QED 0.34
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cccc(C(F)(F)F)c4)c3)c2cc1OC
InChIKey: QPJTXOPHNPRKOS-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 484.43, ALogP 6.1, HBA 6, HBD 2, PSA 94.6, QED 0.34
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cccc(C(C)(C)C)c4)c3)c2cc1OC
InChIKey: XLDWUSQMDJOMMX-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 472.55, ALogP 6.38, HBA 6, HBD 2, PSA 94.6, QED 0.34
Compound (SMILES): COc1cccc(NC(=O)Nc2cccc(Oc3ncnc4cc(OC)c(OC)cc34)c2)c1
InChIKey: ILRHFINBZIHVAO-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 446.46, ALogP 5.09, HBA 7, HBD 2, PSA 103.83, QED 0.41
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4ccc(Cl)cc4)c3)c2cc1OC
InChIKey: SUAVWHXDRSHRAU-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 450.88, ALogP 5.74, HBA 6, HBD 2, PSA 94.6, QED 0.39
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4ccc(C(C)(C)C)cc4)c3)c2cc1OC
InChIKey: BWKRBEKNGFHQLO-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 472.55, ALogP 6.38, HBA 6, HBD 2, PSA 94.6, QED 0.34
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4ccc(Cl)c(C(F)(F)F)c4)c3)c2cc1OC
InChIKey: LFWLHYKPWIJSBE-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 518.88, ALogP 6.76, HBA 6, HBD 2, PSA 94.6, QED 0.29
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)on4)c3C)c2cc1OC
InChIKey: QLLMCJODYDQMKE-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 477.52, ALogP 5.68, HBA 8, HBD 2, PSA 120.63, QED 0.36
Compound (SMILES): COc1cc2ncnc(Oc3ccc(F)c(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OC
InChIKey: BFGHWVXEBAHITM-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 481.48, ALogP 5.51, HBA 8, HBD 2, PSA 120.63, QED 0.37
Compound (SMILES): COc1cc2ncnc(Oc3ccc(Cl)c(NC(=O)Nc4cc(C(C)(C)C)on4)c3)c2cc1OC
InChIKey: SOSHULPZORWFMN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of BRAF V600E mutant-dependent MEK phosphorylation in A375 cells
Measurement: IC50 = 229 nM (pChEMBL 6.639999866485596)
Descriptors: MW 497.94, ALogP 6.02, HBA 8, HBD 2, PSA 120.63, QED 0.33
Compound (SMILES): CN(C)[C@H]1CC[C@@H](c2ccc(OCCCN3CCCCC3)cc2)CC1
InChIKey: NBCFVKKQKAXINS-TYKWCNGQSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [125I]Iodoproxyfan from recombinant human histamine H3 receptor expressed in HEK293 cells after 60 mins
Measurement: Ki = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 344.54, ALogP 4.53, HBA 3, HBD 0, PSA 15.71, QED 0.68
Compound (SMILES): CN(C)[C@H]1CC[C@H](c2ccc(OCCCN3CCCCC3)cc2)CC1
InChIKey: NBCFVKKQKAXINS-XUTJKUGGSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [125I]Iodoproxyfan from recombinant human histamine H3 receptor expressed in HEK293 cells after 60 mins
Measurement: Ki = 0.21 nM (pChEMBL 9.680000305175781)
Descriptors: MW 344.54, ALogP 4.53, HBA 3, HBD 0, PSA 15.71, QED 0.68
Compound (SMILES): c1cc([C@H]2CC[C@@H](N3CCCC3)CC2)ccc1OCCCN1CCCCC1
InChIKey: IIGOTHGDDVVXRO-DKXQDJALSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [125I]Iodoproxyfan from recombinant human histamine H3 receptor expressed in HEK293 cells after 60 mins
Measurement: Ki = 0.33 nM (pChEMBL 9.479999542236328)
Descriptors: MW 370.58, ALogP 5.06, HBA 3, HBD 0, PSA 15.71, QED 0.62
Compound (SMILES): c1cc([C@H]2CC[C@H](N3CCCC3)CC2)ccc1OCCCN1CCCCC1
InChIKey: IIGOTHGDDVVXRO-AFARHQOCSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [125I]Iodoproxyfan from recombinant human histamine H3 receptor expressed in HEK293 cells after 60 mins
Measurement: Ki = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 370.58, ALogP 5.06, HBA 3, HBD 0, PSA 15.71, QED 0.62
Compound (SMILES): c1cc([C@H]2CC[C@H](N3CCOCC3)CC2)ccc1OCCCN1CCCCC1
InChIKey: NFMCJKWXWBIFGH-AFARHQOCSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [125I]Iodoproxyfan from recombinant human histamine H3 receptor expressed in HEK293 cells after 60 mins
Measurement: Ki = 0.41 nM (pChEMBL 9.390000343322754)
Descriptors: MW 386.58, ALogP 4.3, HBA 4, HBD 0, PSA 24.94, QED 0.65