lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): NCCN(CCNC(=O)CCC(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(O)cc1)CCNC(=O)CCC(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(O)cc1.O=C(O)C(F)(F)F
InChIKey: ZCPWOSPECIMESU-UKLKETJRSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human MCF7 cells
Measurement: Ki = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 1605.91
Compound (SMILES): NCCN(CCNC(=O)CCCC(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(O)cc1)CCNC(=O)CCCC(=O)NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(O)cc1.O=C(O)C(F)(F)F
InChIKey: DFTTXCVAQGMFHN-UDCAZBBNSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human MCF7 cells
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 1633.96
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(O)cc1
InChIKey: KUWBXRGRMQZCSS-QHCPKHFHSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human SK-N-MC cells
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 473.58, ALogP 2.59, HBA 4, HBD 6, PSA 140.33, QED 0.14
Compound (SMILES): NCCOCCOCCNC(=O)/N=C(/N)NCCC[C@@H](NC(=O)C(c1ccccc1)c1ccccc1)C(=O)NCc1ccc(O)cc1.O=C(O)C(F)(F)F
InChIKey: JXFDXGIWTUPDDW-XXIQNXCHSA-N
Target: Neuropeptide Y receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25929
Assay: Displacement of [3H]UR-MK114 from human neuropeptide Y receptor type 1 expressed in human SK-N-MC cells
Measurement: Ki = 7.3 nM (pChEMBL 8.140000343322754)
Descriptors: MW 647.78, ALogP 1.71, HBA 7, HBD 7, PSA 202.42, QED 0.06
Compound (SMILES): COc1ccc(COc2cccc(NC(=O)C3CCN(c4ccncc4)CC3)c2)cc1OC
InChIKey: REJHNYWZKUTBBF-UHFFFAOYSA-N
Target: Prothrombin (SINGLE PROTEIN), Bos taurus
UniProt: P00735
Assay: Inhibition of bovine thrombin using D-Phe-Pip-Arg-p-NA as substrate by chromogenic assay
Measurement: Ki = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 447.54, ALogP 4.53, HBA 6, HBD 1, PSA 72.92, QED 0.55
Compound (SMILES): O=C(Nc1cccc(OCc2cc(F)cc(F)c2)c1)C1CCN(c2ccncc2)CC1
InChIKey: ZORXTJQDLSFBOA-UHFFFAOYSA-N
Target: Prothrombin (SINGLE PROTEIN), Bos taurus
UniProt: P00735
Assay: Inhibition of bovine thrombin using D-Phe-Pip-Arg-p-NA as substrate by chromogenic assay
Measurement: Ki = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 423.46, ALogP 4.79, HBA 4, HBD 1, PSA 54.46, QED 0.62
Compound (SMILES): O=C(Nc1cccc(OCc2ccccc2F)c1)C1CCN(c2ccncc2)CC1
InChIKey: DXAPSOAHVMXRKS-UHFFFAOYSA-N
Target: Prothrombin (SINGLE PROTEIN), Bos taurus
UniProt: P00735
Assay: Inhibition of bovine thrombin using D-Phe-Pip-Arg-p-NA as substrate by chromogenic assay
Measurement: Ki = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 405.47, ALogP 4.65, HBA 4, HBD 1, PSA 54.46, QED 0.65
Compound (SMILES): O=C(Nc1cccc(OCc2cccc(F)c2)c1)C1CCN(c2ccncc2)CC1
InChIKey: NTCCWWNRATWWLQ-UHFFFAOYSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin using D-Phe-Pip-Arg-p-NA as substrate by chromogenic assay
Measurement: Ki = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 405.47, ALogP 4.65, HBA 4, HBD 1, PSA 54.46, QED 0.65
Compound (SMILES): O=C(Nc1cccc(OCc2ccc(F)cc2)c1)C1CCN(c2ccncc2)CC1
InChIKey: HPGYXBMGZJDAJR-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of human factor 10a using Z-D-Arg-Gly-Arg-p-NA as substrate by chromogenic assay
Measurement: Ki = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 405.47, ALogP 4.65, HBA 4, HBD 1, PSA 54.46, QED 0.65
Compound (SMILES): O=S1(=O)NCN(C2CC2)c2ccc(F)cc21
InChIKey: FLTMTBPCYAZIKM-UHFFFAOYSA-N
Target: Glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P42262
Assay: Positive allosteric modulation of GluA2 (Q) flop isoform (unknown origin) expressed in HEK293 cells assessed as potentiation of glutamate-evoked calcium flux by fluo-4/AM dye-based fluorescence assay
Measurement: EC50 = 810 nM (pChEMBL 6.090000152587891)
Descriptors: MW 242.28, ALogP 1.04, HBA 3, HBD 1, PSA 49.41, QED 0.8
Compound (SMILES): COc1cc2c(NC3CCN(C(C)C)CC3)nc(N3CCC(F)(F)CC3)nc2cc1OCCCN1CCCC1
InChIKey: RNAMYOYQYRYFQY-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of lysine methyltransferase G9a in human U2OS cells assessed as reduction of H3K9me2 cellular level by immunofluorescence in-cell Western assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 546.71, ALogP 5.02, HBA 8, HBD 1, PSA 65.99, QED 0.42
Compound (SMILES): COc1cccc(C(=O)Nc2cc(C)c(Oc3ccc(O)cc3)c(C)c2)c1
InChIKey: CGWSHFPCZCSZNN-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Mus musculus
UniProt: P19091
Assay: Antagonist activity at androgen receptor in mouse SC3 cells assessed as inhibition of DHT-induced cell growth after 3 days by CCK-8/WST-8 assay
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 363.41, ALogP 5.06, HBA 4, HBD 2, PSA 67.79, QED 0.66
Compound (SMILES): COc1cccc(C(=O)Nc2ccc(Oc3ccc(O)cc3)c(C)c2)c1
InChIKey: IBNFBUZURJLOIX-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Mus musculus
UniProt: P19091
Assay: Antagonist activity at androgen receptor in mouse SC3 cells assessed as inhibition of DHT-induced cell growth after 3 days by CCK-8/WST-8 assay
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 349.39, ALogP 4.75, HBA 4, HBD 2, PSA 67.79, QED 0.7
Compound (SMILES): COc1cccc(C(=O)Nc2ccc(Oc3ccc(O)cc3)cc2)c1
InChIKey: CRULTPXBZBEKFC-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Mus musculus
UniProt: P19091
Assay: Antagonist activity at androgen receptor in mouse SC3 cells assessed as inhibition of DHT-induced cell growth after 3 days by CCK-8/WST-8 assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 335.36, ALogP 4.45, HBA 4, HBD 2, PSA 67.79, QED 0.72
Compound (SMILES): CC(C)OC(=O)N1CCN(c2ccc(NC(=O)c3oc(N4CCCCC4)nc3C(F)(F)F)cn2)CC1
InChIKey: JDNUWBKKCJHGHA-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) preincubated prior to substrate addition
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 510.52, ALogP 4, HBA 8, HBD 1, PSA 104.04, QED 0.64
Compound (SMILES): O=C(Nc1ccc(N2CCN(C(=O)Nc3ccccc3Cl)CC2)nc1)c1oc(N2CCCCC2)nc1C(F)(F)F
InChIKey: ZENSLLXCLNJAMF-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) preincubated prior to substrate addition
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 578, ALogP 5.34, HBA 7, HBD 2, PSA 106.84, QED 0.42
Compound (SMILES): CCCCCn1c2ccccc2c2cc(C(=O)N3CCCCC3)ccc21
InChIKey: NZEVKZAEMSMLMC-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P20272
Assay: Displacement of [3H]-CP55940 from CB1 receptor in rat brain homogenate after 1.5 hrs by microbeta liquid scintillation counting analysis
Measurement: Ki = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 348.49, ALogP 5.61, HBA 2, HBD 0, PSA 25.24, QED 0.55
Compound (SMILES): Cc1cnc(Nc2cc(Cc3ccccc3)nc(N[C@H]3CC[C@H](O)CC3)n2)s1
InChIKey: LHVUZIHFLUPGOR-SAABIXHNSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Inhibition of recombinant human FLAG-tagged ITK using biotinylated GST-SAM68 as substrate after 30 mins
Measurement: Ki = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 395.53, ALogP 4.29, HBA 7, HBD 3, PSA 82.96, QED 0.58
Compound (SMILES): O[C@H]1CC[C@H](Nc2nc(Cc3ccccc3)cc(Nc3nc4ccccc4s3)n2)CC1
InChIKey: CLAFAHXMXSENJP-UAPYVXQJSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Inhibition of GST-tagged full-length ITK (unknown origin) using Ac-EFPIYDFLPAKKK-NH2 as substrate after 35 mins by LC/MS analysis
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 431.57, ALogP 5.14, HBA 7, HBD 3, PSA 82.96, QED 0.39
Compound (SMILES): CCc1ccc2nc(Nc3cc(Cc4ccccc4)nc(N[C@H]4CC[C@H](O)CC4)n3)sc2c1
InChIKey: DPRNXTSMYVCYLJ-XUTJKUGGSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of LRRK2 (unknown origin)
Measurement: IC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 459.62, ALogP 5.7, HBA 7, HBD 3, PSA 82.96, QED 0.33
Compound (SMILES): Cc1cccc(CC(=O)N2CCc3cc(-c4cn(C)c5ncnc(N)c45)ccc32)n1
InChIKey: VYZYOJULVVGQRS-UHFFFAOYSA-N
Target: Eukaryotic translation initiation factor 2-alpha kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NZJ5
Assay: Inhibition of GST-tagged human recombinant PERK by ADP-glo reagent based assay
Measurement: IC50 = 9.7 nM (pChEMBL 8.010000228881836)
Descriptors: MW 398.47, ALogP 3.05, HBA 6, HBD 1, PSA 89.93, QED 0.57
Compound (SMILES): Cc1cccc(CC(=O)N2CCc3c2ccc(-c2cn(C)c4ncnc(N)c24)c3F)n1
InChIKey: PRWSIEBRGXYXAJ-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes using paclitaxel as substrate after 5 to 60 mins by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 416.46, ALogP 3.19, HBA 6, HBD 1, PSA 89.93, QED 0.55
Compound (SMILES): Cn1cc(-c2ccc3c(c2)CCN3C(=O)Cc2cccc(C(F)(F)F)n2)c2c(N)ncnc21
InChIKey: PPJWJOYOOLVOPL-UHFFFAOYSA-N
Target: Eukaryotic translation initiation factor 2-alpha kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NZJ5
Assay: Inhibition of GST-tagged human recombinant PERK by ADP-glo reagent based assay
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 452.44, ALogP 3.76, HBA 6, HBD 1, PSA 89.93, QED 0.51
Compound (SMILES): Cn1cc(-c2ccc3c(c2F)CCN3C(=O)Cc2cccc(C(F)(F)F)n2)c2c(N)ncnc21
InChIKey: QAEKSWBVYBVLNO-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes using paclitaxel as substrate after 5 to 60 mins by LC-MS/MS analysis
Measurement: IC50 = 5830 nM (pChEMBL 5.230000019073486)
Descriptors: MW 470.43, ALogP 3.9, HBA 6, HBD 1, PSA 89.93, QED 0.46
Compound (SMILES): Cc1cc(C)n(CC(=O)N2CCc3c2ccc(-c2cn(C)c4ncnc(N)c24)c3F)n1
InChIKey: HFOKVVVCWLIUBP-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using nifedipine as substrate after 5 to 60 mins by LC-MS/MS analysis
Measurement: IC50 = 20500 nM (pChEMBL 4.690000057220459)
Descriptors: MW 419.46, ALogP 2.76, HBA 7, HBD 1, PSA 94.86, QED 0.55
Compound (SMILES): O=C1OCCc2cc(CCN3CCN(C(=O)Cc4ccc(-n5cnnn5)cc4)CC3)ccc21
InChIKey: UTGNVKDQKQTRCO-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48048
Assay: Inhibition of human ROMK channel-mediated 86Rb+ flux expressed in CHO cells after 35 mins by scintillation counting analysis
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 446.51, ALogP 1.3, HBA 8, HBD 0, PSA 93.45, QED 0.53
Compound (SMILES): Cc1c(CCN2CCN(C(=O)Cc3ccc(-n4cnnn4)cc3)CC2)ccc2c1COC2=O
InChIKey: INGZRGKJUHWGLX-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48048
Assay: Inhibition of human ROMK channel-mediated 86Rb+ flux expressed in CHO cells after 35 mins by scintillation counting analysis
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 446.51, ALogP 1.57, HBA 8, HBD 0, PSA 93.45, QED 0.53
Compound (SMILES): O=C1OCc2c1ccc(CCN1CCN(C(=O)Cc3ccc(-n4cnnn4)cc3)CC1)c2F
InChIKey: OZKZPUAEFNLTGL-UHFFFAOYSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48048
Assay: Inhibition of human ROMK channel-mediated 86Rb+ flux expressed in CHO cells after 35 mins by scintillation counting analysis
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 450.47, ALogP 1.4, HBA 8, HBD 0, PSA 93.45, QED 0.52
Compound (SMILES): O=C1OCc2cc(CCN3CCN(C(=O)Cc4ccc(-n5cnnn5)cc4)CC3)ccc21
InChIKey: LKLRNYYBQWYHND-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 channel (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 432.48, ALogP 1.26, HBA 8, HBD 0, PSA 93.45, QED 0.54
Compound (SMILES): CCCCCn1c2ccc(C(=O)N3CCCCC3)cc2c2ccc(OC)cc21
InChIKey: LHILAHDXYGCIPJ-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P20272
Assay: Displacement of [3H]-CP55940 from CB1 receptor in rat brain homogenate after 1.5 hrs by microbeta liquid scintillation counting analysis
Measurement: Ki = 12.8 nM (pChEMBL 7.889999866485596)
Descriptors: MW 378.52, ALogP 5.62, HBA 3, HBD 0, PSA 34.47, QED 0.52
Compound (SMILES): CCc1nc(N[C@@H]2CCC[C@@H]2C#N)c2cc[nH]c(=O)c2n1
InChIKey: OUAYPLUHINPFJL-MWLCHTKSSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 283.34, ALogP 1.98, HBA 5, HBD 2, PSA 94.46, QED 0.9
Compound (SMILES): N#CC1CCCC1Nc1ncnc2c(=O)[nH]ccc12
InChIKey: RSGDPBGFGVDKNP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 (unknown origin)
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 255.28, ALogP 1.42, HBA 5, HBD 2, PSA 94.46, QED 0.85
Compound (SMILES): COc1cc(-c2cnc3[nH]cc(-c4cnc(N)nc4)c3c2)cc(OC)c1OC
InChIKey: GNZKXRXWADXJOQ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 11 (SINGLE PROTEIN), Mus musculus
UniProt: Q80XI6
Assay: Inhibition of MLK3 in mouse BV2 cells assessed as inhibition of LPS-induced TNFalpha release after 8 hrs by ELISA
Measurement: IC50 = 990 nM (pChEMBL 6)
Descriptors: MW 377.4, ALogP 3.29, HBA 7, HBD 2, PSA 108.17, QED 0.55
Compound (SMILES): CN1CCN(Cc2ccc(-c3cnc4[nH]cc(-c5cnc6[nH]ccc6c5)c4c3)cc2)CC1
InChIKey: GOTKZROZHBWZJH-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Inhibition of wild type human IKKb by high throughput ATP-[33P] radiolabeled assay
Measurement: IC50 = 288 nM (pChEMBL 6.539999961853027)
Descriptors: MW 422.54, ALogP 4.52, HBA 4, HBD 2, PSA 63.84, QED 0.45
Compound (SMILES): CN1CCN(Cc2ccc(-c3cnc4[nH]cc(-c5ccc6[nH]ccc6c5)c4c3)cc2)CC1
InChIKey: QKKIWEILHCXECO-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of wild type human ERK2 by high throughput ATP-[33P] radiolabeled assay
Measurement: IC50 = 6290 nM (pChEMBL 5.199999809265137)
Descriptors: MW 421.55, ALogP 5.13, HBA 3, HBD 2, PSA 50.95, QED 0.42
Compound (SMILES): COc1cc(-c2cnc3[nH]cc(-c4ccc5[nH]ccc5c4)c3c2)cc(OC)c1OC
InChIKey: UQHKXSZPEUNUDH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16584
Assay: Inhibition of MLK3 (unknown origin) after 20 mins by scintillation counting analysis in presence of [33P]-ATP
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 399.45, ALogP 5.4, HBA 4, HBD 2, PSA 72.16, QED 0.41
Compound (SMILES): Nc1ccc(-c2cnc3[nH]cc(-c4ccc5[nH]ccc5c4)c3c2)cn1
InChIKey: YVKIJUOXNIWLHR-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes assessed as inhibition of diclofenac metabolism by HPLC/MS analysis
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 325.38, ALogP 4.36, HBA 3, HBD 3, PSA 83.38, QED 0.45
Compound (SMILES): COc1cc(-c2cnc3[nH]cc(-c4ccc(N)nc4)c3c2)cc(OC)c1OC
InChIKey: DFBYFJSXUCUKLA-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human wild type LRRK2 by qPCR analysis
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 376.42, ALogP 3.9, HBA 6, HBD 2, PSA 95.28, QED 0.55
Compound (SMILES): Nc1ncc(-c2cnc3[nH]cc(-c4ccc5[nH]ccc5c4)c3c2)cn1
InChIKey: MPTRQLXNBJOFSI-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 11 (SINGLE PROTEIN), Mus musculus
UniProt: Q80XI6
Assay: Inhibition of MLK3 in mouse BV2 cells assessed as inhibition of LPS-induced TNFalpha release after 8 hrs by ELISA
Measurement: IC50 = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 326.36, ALogP 3.75, HBA 4, HBD 3, PSA 96.27, QED 0.46
Compound (SMILES): CCn1c(C(=O)N[C@@H](C)CO)ccc1C(CC)(CC)c1ccc(OCC(O)C(C)(C)C)c(C)c1
InChIKey: SLBBZSWGKDNDJZ-JINQPTGOSA-N
Target: Vitamin D3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P11473
Assay: Binding affinity to VDR in scrambled siRNA-transfected human MCF7 cells assessed as cell growth inhibition by measuring reduction in BrdU incorporation after 16 hrs by ELISA
Measurement: IC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 472.67, ALogP 4.82, HBA 5, HBD 3, PSA 83.72, QED 0.44
Compound (SMILES): CN1CC[C@]23c4c5ccc(O)c4O[C@H]2[C@H](NC(=O)/C=C/c2ccccc2)C=C[C@H]3[C@H]1C5
InChIKey: HBGUKHSNIWDVFP-XUZRCCIISA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P33534
Assay: Displacement of [125I]-BNtxA from mouse cloned kappa opioid receptor expressed in CHO cells after 90 mins
Measurement: Ki = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 414.51, ALogP 3.04, HBA 4, HBD 2, PSA 61.8, QED 0.6
Compound (SMILES): O=C(COc1ccc(Cl)cc1)NNC(=S)NCCCCC1CCCCC1
InChIKey: JRAYHZWPXHIVJI-UHFFFAOYSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Homo sapiens
UniProt: P78536
Assay: Inhibition of human TACE after 5 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 397.97, ALogP 3.96, HBA 3, HBD 3, PSA 62.39, QED 0.35
Compound (SMILES): Cc1ccc(-c2csc(=N)n2CC(=O)N2CCN(c3ccccc3)CC2)cc1
InChIKey: QPNYSIWOKUFJDJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of human MAPK1
Measurement: Ki = 2090 nM (pChEMBL 5.679999828338623)
Descriptors: MW 392.53, ALogP 3.35, HBA 5, HBD 1, PSA 52.33, QED 0.74
Compound (SMILES): N=c1scc(-c2ccc(Cl)cc2)n1CC(=O)N1CCN(c2ccccc2)CC1
InChIKey: ISGVIWPJZIQAJO-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of human MAPK1
Measurement: Ki = 501 nM (pChEMBL 6.300000190734863)
Descriptors: MW 412.95, ALogP 3.7, HBA 5, HBD 1, PSA 52.33, QED 0.71
Compound (SMILES): N=c1scc(-c2ccccc2)n1CC(=O)N1CCN(c2ccccc2)CC1
InChIKey: FFEHZWWAKZFKGK-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of human MAPK1
Measurement: Ki = 1730 nM (pChEMBL 5.760000228881836)
Descriptors: MW 378.5, ALogP 3.04, HBA 5, HBD 1, PSA 52.33, QED 0.76
Compound (SMILES): CC(=O)N1CCN(C(=O)Cn2c(-c3ccc(C)cc3)csc2=N)CC1
InChIKey: ZIFWCHUSQIPOCD-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of human MAPK1
Measurement: Ki = 2230 nM (pChEMBL 5.650000095367432)
Descriptors: MW 358.47, ALogP 1.7, HBA 5, HBD 1, PSA 69.4, QED 0.91
Compound (SMILES): CC(=O)N1CCN(C(=O)Cn2c(-c3ccc(Cl)cc3)csc2=N)CC1
InChIKey: PIDHTUREIXPEFO-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of human MAPK1
Measurement: Ki = 778 nM (pChEMBL 6.110000133514404)
Descriptors: MW 378.89, ALogP 2.04, HBA 5, HBD 1, PSA 69.4, QED 0.89
Compound (SMILES): Cc1ccc(-c2csc(=N)n2CC(=O)N2CCN(C)CC2)cc1
InChIKey: RVXLBYMWQICVBU-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of human MAPK1
Measurement: Ki = 1890 nM (pChEMBL 5.71999979019165)
Descriptors: MW 330.46, ALogP 1.78, HBA 5, HBD 1, PSA 52.33, QED 0.93
Compound (SMILES): CC(=O)N1CCN(C(=O)Cn2c(-c3ccccc3)csc2=N)CC1
InChIKey: UJTCLCSSFRMSEH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of human MAPK1
Measurement: Ki = 3670 nM (pChEMBL 5.429999828338623)
Descriptors: MW 344.44, ALogP 1.39, HBA 5, HBD 1, PSA 69.4, QED 0.91
Compound (SMILES): CN1CCN(C(=O)Cn2c(-c3ccc(Cl)cc3)csc2=N)CC1
InChIKey: AXKCLMARXPEYOI-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of human MAPK1
Measurement: Ki = 8840 nM (pChEMBL 5.050000190734863)
Descriptors: MW 350.88, ALogP 2.12, HBA 5, HBD 1, PSA 52.33, QED 0.92
Compound (SMILES): Cc1ccc(-c2csc(=N)n2CC(=O)N2CCOCC2)cc1
InChIKey: MXCHJXBXBFDTNS-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of human MAPK1
Measurement: Ki = 9780 nM (pChEMBL 5.010000228881836)
Descriptors: MW 317.41, ALogP 1.86, HBA 5, HBD 1, PSA 58.32, QED 0.94
Compound (SMILES): CN1CCN(C(=O)Cn2c(-c3ccccc3)csc2=N)CC1
InChIKey: XYYGTTPKVXBPPI-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of human MAPK1
Measurement: Ki = 4890 nM (pChEMBL 5.309999942779541)
Descriptors: MW 316.43, ALogP 1.47, HBA 5, HBD 1, PSA 52.33, QED 0.93
Compound (SMILES): N=c1scc(-c2ccccc2)n1CC(=O)N1CCOCC1
InChIKey: BPAPVVZKFSFVIH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of human MAPK1
Measurement: Ki = 13780 nM (pChEMBL 4.860000133514404)
Descriptors: MW 303.39, ALogP 1.55, HBA 5, HBD 1, PSA 58.32, QED 0.94
Compound (SMILES): N=c1scc(-c2ccc(Cl)cc2)n1CC(=O)N1CCOCC1
InChIKey: IHOGKRIRHORAHV-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of human MAPK1
Measurement: Ki = 9180 nM (pChEMBL 5.039999961853027)
Descriptors: MW 337.83, ALogP 2.21, HBA 5, HBD 1, PSA 58.32, QED 0.93
Compound (SMILES): C=CC(=O)Nc1ccc(-n2c(=O)cnc3cnc(Nc4ccc(Cl)cc4)nc32)cc1
InChIKey: YQVNLEYHEXIBNV-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 7580 nM (pChEMBL 5.119999885559082)
Descriptors: MW 418.84, ALogP 3.7, HBA 7, HBD 2, PSA 101.8, QED 0.48
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(Cl)cc4)nc32)c1
InChIKey: NPYHVKHWRDSLAV-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 418.84, ALogP 3.7, HBA 7, HBD 2, PSA 101.8, QED 0.48
Compound (SMILES): C=CC(=O)Nc1ccc(-n2c(=O)cnc3cnc(Nc4ccc(N5CCOCC5)cc4)nc32)cc1
InChIKey: CHFSRPYBDAIBQR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 4168 nM (pChEMBL 5.380000114440918)
Descriptors: MW 469.51, ALogP 2.88, HBA 9, HBD 2, PSA 114.27, QED 0.41
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(N5CCOCC5)cc4)nc32)c1
InChIKey: NXZQKEJXOSVRFZ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 7.94 nM (pChEMBL 8.100000381469727)
Descriptors: MW 469.51, ALogP 2.88, HBA 9, HBD 2, PSA 114.27, QED 0.41
Compound (SMILES): C=CC(=O)Nc1ccc(-n2c(=O)cnc3cnc(Nc4ccc(N5CCN(C)CC5)cc4)nc32)cc1
InChIKey: DRGNKFXIAXKCCX-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 1260 nM (pChEMBL 5.900000095367432)
Descriptors: MW 482.55, ALogP 2.8, HBA 9, HBD 2, PSA 108.28, QED 0.4
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(N5CCN(C)CC5)cc4)nc32)c1
InChIKey: JJQDZMPHVLCCFS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R mutant (unknown origin) using Tyr 4 peptide as substrate after 1.5 hrs by FRET-based Z'-LYTE assay
Measurement: IC50 = 1.32 nM (pChEMBL 8.880000114440918)
Descriptors: MW 482.55, ALogP 2.8, HBA 9, HBD 2, PSA 108.28, QED 0.4
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(N5CCCCC5)cc4)nc32)c1
InChIKey: VJFSMDWEMFOWDK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 467.53, ALogP 4.03, HBA 8, HBD 2, PSA 105.04, QED 0.41
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(N5CCCC5)cc4)nc32)c1
InChIKey: HKNZEEWNPHTWIR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 98 nM (pChEMBL 7.010000228881836)
Descriptors: MW 453.51, ALogP 3.64, HBA 8, HBD 2, PSA 105.04, QED 0.43
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(N(CC)CC)cc4)nc32)c1
InChIKey: BIUVCZQWTOSTRS-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 455.52, ALogP 3.89, HBA 8, HBD 2, PSA 105.04, QED 0.39
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(NC(C)=O)cc4)nc32)c1
InChIKey: JIJDVLXBQGQRQM-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin) using Tyr 4 peptide as substrate after 1.5 hrs by FRET-based Z'-LYTE assay
Measurement: IC50 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 441.45, ALogP 3, HBA 8, HBD 3, PSA 130.9, QED 0.39
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(C(N)=O)cc4)nc32)c1
InChIKey: JWNAINYXINYHML-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R mutant (unknown origin) using Tyr 4 peptide as substrate after 1.5 hrs by FRET-based Z'-LYTE assay
Measurement: IC50 = 11.8 nM (pChEMBL 7.929999828338623)
Descriptors: MW 427.42, ALogP 2.14, HBA 8, HBD 3, PSA 144.89, QED 0.4
Compound (SMILES): C=CC(=O)Nc1ccc(-n2c(=O)cnc3cnc(Nc4ccc(N5CCN(C)CC5)cc4OC)nc32)cc1
InChIKey: BMYBPXJXNNXUJF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 812 nM (pChEMBL 6.090000152587891)
Descriptors: MW 512.57, ALogP 2.8, HBA 10, HBD 2, PSA 117.51, QED 0.36
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(N5CCN(C)CC5)cc4OC)nc32)c1
InChIKey: YJAJTLZIWHYGPF-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 2.36 nM (pChEMBL 8.630000114440918)
Descriptors: MW 512.57, ALogP 2.8, HBA 10, HBD 2, PSA 117.51, QED 0.36
Compound (SMILES): C=CC(=O)Nc1ccc(-n2c(=O)c(C)nc3cnc(Nc4ccc(OC)cc4)nc32)cc1
InChIKey: WZUJQAJDFCNKQS-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 206 nM (pChEMBL 6.690000057220459)
Descriptors: MW 428.45, ALogP 3.36, HBA 8, HBD 2, PSA 111.03, QED 0.45
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)c(C)nc3cnc(Nc4ccc(OC)cc4)nc32)c1
InChIKey: FGPPXNCHKYRZCI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Inhibition of human ITK using poly-Glu-Tyr (4:1) as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 46.1 nM (pChEMBL 7.340000152587891)
Descriptors: MW 428.45, ALogP 3.36, HBA 8, HBD 2, PSA 111.03, QED 0.45