lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C/C=C1\NC(=O)c2csc(n2)CNC(=O)C[C@@H](/C=C/CCSC(=O)CCCCCCC)OC(=O)[C@H](C(C)C)NC1=O
InChIKey: WCZYLKXWWUKEBA-QUDUTUPQSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of C-terminal His-tagged recombinant human HDAC3 (1 to 428 residues)/N-terminal GST-tagged recombinant human NCoR2 (395 to 489 residues) co-expressed in baculovirus infected Sf9 cells using fluorometric substrate measured after 60 mins by FRET assay
Measurement: IC50 = 8.9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 606.81, ALogP 4.42, HBA 9, HBD 3, PSA 143.56, QED 0.15
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Binding affinity to recombinant human JAK2 kinase domain (840 to 1132 residues) assessed as dissociation constant by ITC analysis
Measurement: Kd = 10.7 nM (pChEMBL 7.96999979019165)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 JH1 domain (unknown origin) using FITC-Ahx-KKSRGDYMTMQIG-NH2 peptide as substrate incubated for 60 mins in the presence of ATP by caliper microfluidic mobility shift technology
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): C[C@@H]1Cc2c([nH]c3ccccc23)[C@@H](c2c(F)cc(/C=C/C(=O)O)cc2F)N1CC(C)(C)F
InChIKey: DFBDRVGWBHBJNR-BBNFHIFMSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to human wild type ERalpha ligand binding domain
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 442.48, ALogP 5.63, HBA 2, HBD 2, PSA 56.33, QED 0.5
Compound (SMILES): COc1cc2ncnc(Nc3cccc(Cl)c3F)c2cc1OC(=O)N1CCN(C)C[C@H]1C
InChIKey: MXDSJQHFFDGFDK-CYBMUJFWSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 459.91, ALogP 4.31, HBA 7, HBD 1, PSA 79.82, QED 0.62
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lyn (SINGLE PROTEIN), Homo sapiens
UniProt: P07948
Assay: Inhibition of human recombinant Lyn
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): COc1ccc(CC[C@@H](OC(=O)[C@@H]2CCCCN2C(=O)[C@H](c2cc(OC)c(OC)c(OC)c2)C2CCCCC2)c2cccc(OCCN3CCOCC3)c2)cc1OC
InChIKey: ZDBWLRLGUBSLPG-FDHYQTMZSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: GPCRScan assay: inhibition of 5-HT2C
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 803.01, ALogP 7.4, HBA 11, HBD 0, PSA 114.46, QED 0.12
Compound (SMILES): O=C(/C=C/c1ccc(O)cc1)OCCc1ccc(O)cc1
InChIKey: ZCFLGZLKECDZFW-BJMVGYQFSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human carbonic anhydrase 14 preincubated for 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 284.31, ALogP 2.9, HBA 4, HBD 2, PSA 66.76, QED 0.65
Compound (SMILES): C/C=C1\NC(=O)c2csc(n2)CNC(=O)C[C@@H](/C=C/CCSC(=O)CCCCCCC)OC(=O)[C@H](C(C)C)NC1=O
InChIKey: WCZYLKXWWUKEBA-QUDUTUPQSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human full length C-terminal His- tagged HDAC2 (1 to 488 residues) expressed in Sf9 insect cells using fluorometric substrate measured after 60 mins by FRET assay
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 606.81, ALogP 4.42, HBA 9, HBD 3, PSA 143.56, QED 0.15
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2-mediated erythropoietin-induced STAT5 phosphorylation in human TF-1 cells pretreated for 60 mins followed by erythropoietin addition and measured after 15 mins by pacific orange/pacific blue NHS esters based Beckmann coulter flow cytometer
Measurement: IC50 = 488 nM (pChEMBL 6.309999942779541)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 JH1 domain (unknown origin) using Carboxyfluorescein-Ahx-GGEEEEYFELVKKKK peptide as substrate incubated for 60 mins in the presence of ATP by caliper microfluidic mobility shift technology
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): C[C@@H]1Cc2c([nH]c3ccccc23)[C@@H](c2c(F)cc(/C=C/C(=O)O)cc2F)N1CC(C)(C)F
InChIKey: DFBDRVGWBHBJNR-BBNFHIFMSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to human ERalpha D538G mutant ligand binding domain
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 442.48, ALogP 5.63, HBA 2, HBD 2, PSA 56.33, QED 0.5
Compound (SMILES): COc1cc2ncnc(Nc3cccc(Cl)c3F)c2cc1OC(=O)N1CCN(C)C[C@H]1C
InChIKey: MXDSJQHFFDGFDK-CYBMUJFWSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 (unknown origin)
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 459.91, ALogP 4.31, HBA 7, HBD 1, PSA 79.82, QED 0.62
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of human recombinant Lck
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): COc1ccc(CC[C@@H](OC(=O)[C@@H]2CCCCN2C(=O)[C@H](c2cc(OC)c(OC)c(OC)c2)C2CCCCC2)c2cccc(OCCN3CCOCC3)c2)cc1OC
InChIKey: ZDBWLRLGUBSLPG-FDHYQTMZSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: GPCRScan assay: inhibition of D2
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 803.01, ALogP 7.4, HBA 11, HBD 0, PSA 114.46, QED 0.12
Compound (SMILES): C/C=C1\NC(=O)c2csc(n2)CNC(=O)C[C@@H](/C=C/CCSC(=O)CCCCCCC)OC(=O)[C@H](C(C)C)NC1=O
InChIKey: WCZYLKXWWUKEBA-QUDUTUPQSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human full length C-terminal His-tagged HDAC8 expressed in baculovirus infected Sf9 insect cells using fluorometric substrate measured after 60 mins by FRET assay
Measurement: IC50 = 3960 nM (pChEMBL 5.400000095367432)
Descriptors: MW 606.81, ALogP 4.42, HBA 9, HBD 3, PSA 143.56, QED 0.15
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 μL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hour and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a PHERA star plate reader (BMG, Cary, N.C.).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 JH1 domain (unknown origin) using Carboxyfluorescein-Ahx-GGEEEEYFELVKKKK peptide as substrate incubated for 60 mins in the presence of ATP by caliper microfluidic mobility shift technology
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): C[C@@H]1Cc2c([nH]c3ccccc23)[C@@H](c2c(F)cc(/C=C/C(=O)O)cc2F)N1CC(C)(C)F
InChIKey: DFBDRVGWBHBJNR-BBNFHIFMSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to human ERalpha Y537S mutant ligand binding domain
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 442.48, ALogP 5.63, HBA 2, HBD 2, PSA 56.33, QED 0.5
Compound (SMILES): COc1cc2ncnc(Nc3cccc(Cl)c3F)c2cc1OC(=O)N1CCN(C)C[C@H]1C
InChIKey: MXDSJQHFFDGFDK-CYBMUJFWSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 459.91, ALogP 4.31, HBA 7, HBD 1, PSA 79.82, QED 0.62
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of human recombinant JNK3
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): COc1ccc(CC[C@@H](OC(=O)[C@@H]2CCCCN2C(=O)[C@H](c2cc(OC)c(OC)c(OC)c2)C2CCCCC2)c2cccc(OCCN3CCOCC3)c2)cc1OC
InChIKey: ZDBWLRLGUBSLPG-FDHYQTMZSA-N
Target: Histamine H4 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3N8
Assay: GPCRScan assay: inhibition of H4
Measurement: Ki = 3382 nM (pChEMBL 5.46999979019165)
Descriptors: MW 803.01, ALogP 7.4, HBA 11, HBD 0, PSA 114.46, QED 0.12
Compound (SMILES): C/C=C1\NC(=O)c2csc(n2)CNC(=O)C[C@@H](/C=C/CCSC(=O)CCCCCCC)OC(=O)[C@H](C(C)C)NC1=O
InChIKey: WCZYLKXWWUKEBA-QUDUTUPQSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human full length N-terminal GST-tagged HDAC6 expressed in Sf9 cells using fluorogenic substrate measured after 60 mins by FRET assay
Measurement: IC50 = 1810 nM (pChEMBL 5.739999771118164)
Descriptors: MW 606.81, ALogP 4.42, HBA 9, HBD 3, PSA 143.56, QED 0.15
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: TAM Kinase Assay: The kinase assay buffer contained 50 mM HEPES, pH7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% NP-40 and 2 mM DTT. 0.1 ul test compounds dissolved in DMSO were transferred from compound plates to white 384-well assay plates (Greiner LUMITRAC plates). The final concentration of DMSO was 1.25%. Enzyme solutions of 5.1 nM phosphor-Axl (see Axl autophosphorylation assay above), or 0.0625 nM c-Mer (Carna Biosciences, 08-108), or 0.366 nM Tyro3 (Life Technologies, PR7480A) were prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide SEQ ID NO: 1 (Quality Controlled Biochemicals, MA) dissolved in DMSO was diluted to 1 uM in assay buffer containing 2000 uM ATP. 4 ul enzyme solution (or assay buffer for the enzyme blank) was added to the appropriate wells in each plate, and then 4 ul/well substrate solution was added to initiate the reaction. The plate was protected from light and incubated at room temperature for 60 min. The reaction was stopped by adding 4 ul detection solution containing 50 mM Tris-HCl, pH7.8, 150 mM NaCl, 0.05% BSA, 45 mM EDTA, 180 nM SA-APC (Perkin Elmer, CR130-100) and 3 nM Eu¿W1024 anti-phosphotyrosine PY20 (Perkin Elmer, AD0067). The plate was incubated for 1 h at room temperature, and HTRF (homogenous time resolved fluorescence) signal was measured on a PHERAstar FS plate reader (BMG labtech). Percentage of inhibition was calculated for each concentration and IC50 value was generated from curve fitting with GraphPad Prism software.
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 (unknown origin) by caliper technology
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): COc1cc2ncnc(Nc3cccc(Cl)c3F)c2cc1OC(=O)N1CCN(C)C[C@H]1C
InChIKey: MXDSJQHFFDGFDK-CYBMUJFWSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 459.91, ALogP 4.31, HBA 7, HBD 1, PSA 79.82, QED 0.62
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human recombinant JAK3
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): COc1ccc(CC[C@@H](OC(=O)[C@@H]2CCCCN2C(=O)[C@H](c2cc(OC)c(OC)c(OC)c2)C2CCCCC2)c2cccc(OCCN3CCOCC3)c2)cc1OC
InChIKey: ZDBWLRLGUBSLPG-FDHYQTMZSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: GPCRScan assay: inhibition of Sigma 2
Measurement: Ki = 226 nM (pChEMBL 6.650000095367432)
Descriptors: MW 803.01, ALogP 7.4, HBA 11, HBD 0, PSA 114.46, QED 0.12
Compound (SMILES): C/C=C1\NC(=O)c2csc(n2)CNC(=O)C[C@@H](/C=C/CCSC(=O)CCCCCCC)OC(=O)[C@H](C(C)C)NC1=O
InChIKey: WCZYLKXWWUKEBA-QUDUTUPQSA-N
Target: Polyamine deacetylase HDAC10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q969S8
Assay: Inhibition of recombinant human N-terminal FLAG tagged HDAC10 (2 to 631 residues) expressed in baculovirus infected Sf9 insect cells using fluorogenic substrate measured after 60 mins by FRET assay
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 606.81, ALogP 4.42, HBA 9, HBD 3, PSA 143.56, QED 0.15
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: TAM Kinase Assay: The kinase assay buffer contained 50 mM HEPES, pH7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% NP-40 and 2 mM DTT. 0.1 ul test compounds dissolved in DMSO were transferred from compound plates to white 384-well assay plates (Greiner LUMITRAC plates). The final concentration of DMSO was 1.25%. Enzyme solutions of 5.1 nM phosphor-Axl (see Axl autophosphorylation assay above), or 0.0625 nM c-Mer (Carna Biosciences, 08-108), or 0.366 nM Tyro3 (Life Technologies, PR7480A) were prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide SEQ ID NO: 1 (Quality Controlled Biochemicals, MA) dissolved in DMSO was diluted to 1 uM in assay buffer containing 2000 uM ATP. 4 ul enzyme solution (or assay buffer for the enzyme blank) was added to the appropriate wells in each plate, and then 4 ul/well substrate solution was added to initiate the reaction. The plate was protected from light and incubated at room temperature for 60 min. The reaction was stopped by adding 4 ul detection solution containing 50 mM Tris-HCl, pH7.8, 150 mM NaCl, 0.05% BSA, 45 mM EDTA, 180 nM SA-APC (Perkin Elmer, CR130-100) and 3 nM Eu¿W1024 anti-phosphotyrosine PY20 (Perkin Elmer, AD0067). The plate was incubated for 1 h at room temperature, and HTRF (homogenous time resolved fluorescence) signal was measured on a PHERAstar FS plate reader (BMG labtech). Percentage of inhibition was calculated for each concentration and IC50 value was generated from curve fitting with GraphPad Prism software.
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 in human M07E cells assessed as reduction of IL-15 stimulated STAT phosphorylation preincubated for 30 mins followed by IL-15 stimulation and measured after 15 mins by flow cytometry analysis
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): COc1cc2ncnc(Nc3cccc(Cl)c3F)c2cc1OC(=O)N1CCN(C)C[C@H]1C
InChIKey: MXDSJQHFFDGFDK-CYBMUJFWSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 459.91, ALogP 4.31, HBA 7, HBD 1, PSA 79.82, QED 0.62
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Inhibition of human recombinant IRE1
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): COc1ccc(CC[C@@H](OC(=O)[C@@H]2CCCCN2C(=O)[C@H](c2cc(OC)c(OC)c(OC)c2)C2CCCCC2)c2cccc(OCCN3CCOCC3)c2)cc1OC
InChIKey: ZDBWLRLGUBSLPG-FDHYQTMZSA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13451
Assay: Displacement of iFit-FL from FKBP51 (unknown origin) by fluorescence polarization assay
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 803.01, ALogP 7.4, HBA 11, HBD 0, PSA 114.46, QED 0.12
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: TAM Kinase Assay: The kinase assay buffer contained 50 mM HEPES, pH7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% NP-40 and 2 mM DTT. 0.1 ul test compounds dissolved in DMSO were transferred from compound plates to white 384-well assay plates (Greiner LUMITRAC plates). The final concentration of DMSO was 1.25%. Enzyme solutions of 5.1 nM phosphor-Axl (see Axl autophosphorylation assay above), or 0.0625 nM c-Mer (Carna Biosciences, 08-108), or 0.366 nM Tyro3 (Life Technologies, PR7480A) were prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide SEQ ID NO: 1 (Quality Controlled Biochemicals, MA) dissolved in DMSO was diluted to 1 uM in assay buffer containing 2000 uM ATP. 4 ul enzyme solution (or assay buffer for the enzyme blank) was added to the appropriate wells in each plate, and then 4 ul/well substrate solution was added to initiate the reaction. The plate was protected from light and incubated at room temperature for 60 min. The reaction was stopped by adding 4 ul detection solution containing 50 mM Tris-HCl, pH7.8, 150 mM NaCl, 0.05% BSA, 45 mM EDTA, 180 nM SA-APC (Perkin Elmer, CR130-100) and 3 nM Eu¿W1024 anti-phosphotyrosine PY20 (Perkin Elmer, AD0067). The plate was incubated for 1 h at room temperature, and HTRF (homogenous time resolved fluorescence) signal was measured on a PHERAstar FS plate reader (BMG labtech). Percentage of inhibition was calculated for each concentration and IC50 value was generated from curve fitting with GraphPad Prism software.
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of JAK1/TYK2 in human M07E cells assessed as reduction of IFN alpha stimulated STAT phosphorylation preincubated for 30 mins followed by IFN alpha stimulation and measured after 15 mins by flow cytometry method
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): COc1cc2ncnc(Nc3cccc(Cl)c3F)c2cc1OC(=O)N1CCN(C)C[C@H]1C
InChIKey: MXDSJQHFFDGFDK-CYBMUJFWSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 459.91, ALogP 4.31, HBA 7, HBD 1, PSA 79.82, QED 0.62
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of human recombinant IGF-1R
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): COc1ccc(CC[C@@H](OC(=O)[C@@H]2CCCCN2C(=O)[C@H](c2cc(OC)c(OC)c(OC)c2)C2CCCCC2)c2cccc(OCCN3CCOCC3)c2)cc1OC
InChIKey: ZDBWLRLGUBSLPG-FDHYQTMZSA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q02790
Assay: Binding affinity to FKBP52 (unknown origin) assessed as inhibition constant by fluorescence polarization assay
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 803.01, ALogP 7.4, HBA 11, HBD 0, PSA 114.46, QED 0.12
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: TAM Enzymatic Assay: The kinase assay buffer contained 50 mM HEPES, pH7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% NP-40 and 2 mM DTT. 0.1 ul test compounds dissolved in DMSO were transferred from compound plates to white 384-well assay plates (Greiner LUMITRAC plates). The final concentration of DMSO was 1.25%. Enzyme solutions of 5.1 nM phosphor-Axl, or 0.0625 nM c-Mer (Carna Biosciences, 08-108), or 0.366 nM Tyro3 (Life Technologies, PR7480A) were prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide SEQ ID NO: 1 (Quality Controlled Biochemicals, MA) dissolved in DMSO was diluted to 1 uM in assay buffer containing 2000 uM ATP. 4 ul enzyme solution (or assay buffer for the enzyme blank) was added to the appropriate wells in each plate, and then 4 ul/well substrate solution was added to initiate the reaction. The plate was protected from light and incubated at room temperature for 60 min. The reaction was stopped by adding 4 ul detection solution containing 50 mM Tris-HCl, pH7.8, 150 mM NaCl, 0.05% BSA, 45 mM EDTA, 180 nM SA-APC (Perkin Elmer, CR130-100) and 3 nM Eu-W1024 anti-phosphotyrosine PY20 (Perkin Elmer, AD0067). The plate was incubated for 1 h at room temperature, and HTRF (homogenous time resolved fluorescence) signal was measured on a PHERAstar FS plate reader (BMG labtech). Percentage of inhibition was calculated for each concentration and IC50 value was generated from curve fitting with GraphPad Prism software.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 in human blood assessed as reduction of IL-2 stimulated STAT phosphorylation preincubated for 30 mins followed by IL-2 stimulation and measured after 15 mins by flow cytometry method
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): COc1cc2ncnc(Nc3cccc(Cl)c3F)c2cc1OC(=O)N1CCN(C)C[C@H]1C
InChIKey: MXDSJQHFFDGFDK-CYBMUJFWSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 459.91, ALogP 4.31, HBA 7, HBD 1, PSA 79.82, QED 0.62
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of human recombinant GSK3beta
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: TAM Enzymatic Assay: The kinase assay buffer contained 50 mM HEPES, pH7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% NP-40 and 2 mM DTT. 0.1 ul test compounds dissolved in DMSO were transferred from compound plates to white 384-well assay plates (Greiner LUMITRAC plates). The final concentration of DMSO was 1.25%. Enzyme solutions of 5.1 nM phosphor-Axl, or 0.0625 nM c-Mer (Carna Biosciences, 08-108), or 0.366 nM Tyro3 (Life Technologies, PR7480A) were prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide SEQ ID NO: 1 (Quality Controlled Biochemicals, MA) dissolved in DMSO was diluted to 1 uM in assay buffer containing 2000 uM ATP. 4 ul enzyme solution (or assay buffer for the enzyme blank) was added to the appropriate wells in each plate, and then 4 ul/well substrate solution was added to initiate the reaction. The plate was protected from light and incubated at room temperature for 60 min. The reaction was stopped by adding 4 ul detection solution containing 50 mM Tris-HCl, pH7.8, 150 mM NaCl, 0.05% BSA, 45 mM EDTA, 180 nM SA-APC (Perkin Elmer, CR130-100) and 3 nM Eu-W1024 anti-phosphotyrosine PY20 (Perkin Elmer, AD0067). The plate was incubated for 1 h at room temperature, and HTRF (homogenous time resolved fluorescence) signal was measured on a PHERAstar FS plate reader (BMG labtech). Percentage of inhibition was calculated for each concentration and IC50 value was generated from curve fitting with GraphPad Prism software.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Affinity Phenotypic Cellular interaction: (SureFire Assay kit (JAK1 dependent phosphorylation of STAT3, induced by IL-6 in TF-1 cells)) EUB0000644a JAK1
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): COc1cc2ncnc(Nc3cccc(Cl)c3F)c2cc1OC(=O)N1CCN(C)C[C@H]1C
InChIKey: MXDSJQHFFDGFDK-CYBMUJFWSA-N
Target: Cytochrome P450 3A5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20815
Assay: Inhibition of CYP3A5 (unknown origin)
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 459.91, ALogP 4.31, HBA 7, HBD 1, PSA 79.82, QED 0.62
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Fyn (SINGLE PROTEIN), Homo sapiens
UniProt: P06241
Assay: Inhibition of human recombinant Fyn
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: TAM Enzymatic Assay: The kinase assay buffer contained 50 mM HEPES, pH7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% NP-40 and 2 mM DTT. 0.1 ul test compounds dissolved in DMSO were transferred from compound plates to white 384-well assay plates (Greiner LUMITRAC plates). The final concentration of DMSO was 1.25%. Enzyme solutions of 5.1 nM phosphor-Axl, or 0.0625 nM c-Mer (Carna Biosciences, 08-108), or 0.366 nM Tyro3 (Life Technologies, PR7480A) were prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide SEQ ID NO: 1 (Quality Controlled Biochemicals, MA) dissolved in DMSO was diluted to 1 uM in assay buffer containing 2000 uM ATP. 4 ul enzyme solution (or assay buffer for the enzyme blank) was added to the appropriate wells in each plate, and then 4 ul/well substrate solution was added to initiate the reaction. The plate was protected from light and incubated at room temperature for 60 min. The reaction was stopped by adding 4 ul detection solution containing 50 mM Tris-HCl, pH7.8, 150 mM NaCl, 0.05% BSA, 45 mM EDTA, 180 nM SA-APC (Perkin Elmer, CR130-100) and 3 nM Eu-W1024 anti-phosphotyrosine PY20 (Perkin Elmer, AD0067). The plate was incubated for 1 h at room temperature, and HTRF (homogenous time resolved fluorescence) signal was measured on a PHERAstar FS plate reader (BMG labtech). Percentage of inhibition was calculated for each concentration and IC50 value was generated from curve fitting with GraphPad Prism software.
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Affinity Phenotypic Cellular interaction: (Cytokine potency assay (cytokine IL-6, JAK1, pSTAT3 in TF-1 cells)) EUB0000644a JAK1
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): COc1cc2ncnc(Nc3cccc(Cl)c3F)c2cc1OC(=O)N1CCN(C)C[C@H]1C
InChIKey: MXDSJQHFFDGFDK-CYBMUJFWSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR using poly[Glu:Tyr] (4:1) as substrate measured after 20 mins in presence of [gamma33P]ATP by filter-binding assay
Measurement: IC50 < 0.5 nM (pChEMBL 9.300999641418457)
Descriptors: MW 459.91, ALogP 4.31, HBA 7, HBD 1, PSA 79.82, QED 0.62
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human recombinant FGFR2
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: TAM Enzymatic Assay: The kinase assay buffer contained 50 mM HEPES, pH7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% NP-40 and 2 mM DTT. 0.1 ul test compounds dissolved in DMSO were transferred from compound plates to white 384-well assay plates (Greiner LUMITRAC plates). The final concentration of DMSO was 1.25%. Enzyme solutions of 5.1 nM phosphor-Axl, or 0.0625 nM c-Mer (Carna Biosciences, 08-108), or 0.366 nM Tyro3 (Life Technologies, PR7480A) were prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide SEQ ID NO: 1 (Quality Controlled Biochemicals, MA) dissolved in DMSO was diluted to 1 uM in assay buffer containing 2000 uM ATP. 4 ul enzyme solution (or assay buffer for the enzyme blank) was added to the appropriate wells in each plate, and then 4 ul/well substrate solution was added to initiate the reaction. The plate was protected from light and incubated at room temperature for 60 min. The reaction was stopped by adding 4 ul detection solution containing 50 mM Tris-HCl, pH7.8, 150 mM NaCl, 0.05% BSA, 45 mM EDTA, 180 nM SA-APC (Perkin Elmer, CR130-100) and 3 nM Eu-W1024 anti-phosphotyrosine PY20 (Perkin Elmer, AD0067). The plate was incubated for 1 h at room temperature, and HTRF (homogenous time resolved fluorescence) signal was measured on a PHERAstar FS plate reader (BMG labtech). Percentage of inhibition was calculated for each concentration and IC50 value was generated from curve fitting with GraphPad Prism software.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Affinity Phenotypic Cellular interaction: (Cytokine potency assay (cytokine IL-6, JAK1, pSTAT3 in CD14+whole blood cells)) EUB0000644a JAK1
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Fes/Fps (SINGLE PROTEIN), Homo sapiens
UniProt: P07332
Assay: Inhibition of human recombinant Fes
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: TAM Enzymatic Assay: The kinase assay buffer contained 50 mM HEPES, pH7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% NP-40 and 2 mM DTT. 0.1 ul test compounds dissolved in DMSO were transferred from compound plates to white 384-well assay plates (Greiner LUMITRAC plates). The final concentration of DMSO was 1.25%. Enzyme solutions of 5.1 nM phosphor-Axl, or 0.0625 nM c-Mer (Carna Biosciences, 08-108), or 0.366 nM Tyro3 (Life Technologies, PR7480A) were prepared in assay buffer. A 1 mM stock solution of peptide substrate Biotin-EQEDEPEGDYFEWLE-amide SEQ ID NO: 1 (Quality Controlled Biochemicals, MA) dissolved in DMSO was diluted to 1 uM in assay buffer containing 2000 uM ATP. 4 ul enzyme solution (or assay buffer for the enzyme blank) was added to the appropriate wells in each plate, and then 4 ul/well substrate solution was added to initiate the reaction. The plate was protected from light and incubated at room temperature for 60 min. The reaction was stopped by adding 4 ul detection solution containing 50 mM Tris-HCl, pH7.8, 150 mM NaCl, 0.05% BSA, 45 mM EDTA, 180 nM SA-APC (Perkin Elmer, CR130-100) and 3 nM Eu-W1024 anti-phosphotyrosine PY20 (Perkin Elmer, AD0067). The plate was incubated for 1 h at room temperature, and HTRF (homogenous time resolved fluorescence) signal was measured on a PHERAstar FS plate reader (BMG labtech). Percentage of inhibition was calculated for each concentration and IC50 value was generated from curve fitting with GraphPad Prism software.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Affinity Phenotypic Cellular interaction: (Cytokine potency assay (cytokine IL-6, JAK1, pSTAT3 in CD3+whole blood cells)) EUB0000644a JAK1
Measurement: IC50 = 207 nM (pChEMBL 6.679999828338623)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15303
Assay: Inhibition of human recombinant ErbB4
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzyme Assay: The kinase reaction was conducted in clear-bottom 96-well plate from Thermo Fisher Scientific in a final volume of 24 μL. Inhibitors were first diluted serially in DMSO and added to the plate wells before the addition of other reaction components. The final concentration of DMSO in the assay was 0.5%. The PI3K assays were carried out at room temperature in 20 mM MOPS, pH 6.7, 10 mM MgCl2, 5 mM DTT and CHAPS 0.03%. The reaction mixture was prepared containing 50 μM PIP2, kinase and varying concentration of inhibitors. Reactions were initiated by the addition of ATP containing 2.2 μCi [γ-33P]ATP to a final concentration of 1000 μM. The final concentration of PI3K isoforms α, β, δ and γ in the assay were 1.3, 9.4, 2.9 and 10.8 nM respectively. Reactions were incubated for 180 min and terminated by the addition of 100 μL of 1 M potassium phosphate pH 8.0, 30 mM EDTA quench buffer. A 100 μL aliquot of the reaction solution was then transferred to 96-well Millipore MultiScreen IP 0.45 μm PVDF filter plate (The filter plate was prewetted with 200 μL 100% ethanol, distilled water, and 1 M potassium phosphate pH 8.0, respectively). The filter plate was aspirated on a Millipore Manifold under vacuum and washed with 18×200 μL wash buffer containing 1 M potassium phosphate pH 8.0 and 1 mM ATP. After drying by aspiration and blotting, the plate was air dried in an incubator at 37° C. overnight. Packard TopCount adapter (Millipore) was then attached to the plate followed with addition of 120 μL Microscint 20 scintillation cocktail (Perkin Elmer) in each well. After the plate sealing, the radioactivity of the product was determined by scintillation counting on Topcount (Perkin-Elmer).
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Affinity Phenotypic Cellular interaction: (Cytokine potency assay (cytokine OSM, JAK1, pSTAT3 in TF-1 cells)) EUB0000644a JAK1
Measurement: IC50 = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of human recombinant ErbB2
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.).
Measurement: IC50 > 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Affinity Phenotypic Cellular interaction: (Cytokine potency assay (cytokine EPO, JAK2, pSTAT5 in UT7 cells)) EUB0000644a JAK1
Measurement: IC50 = 649 nM (pChEMBL 6.190000057220459)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Ephrin type-B receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29323
Assay: Inhibition of human recombinant EphB2
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.).
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Affinity Phenotypic Cellular interaction: (Cytokine potency assay (cytokine IL-2, JAK1/3, pSTAT5 in T-blast cells)) EUB0000644a JAK1
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human recombinant EGFR
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Affinity Phenotypic Cellular interaction: (Cytokine potency assay (cytokine IL-15, JAK1/3, pSTAT5 in T-blast cells)) EUB0000644a JAK1
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Myotonin-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q09013
Assay: Inhibition of human recombinant DMPK
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Affinity Phenotypic Cellular interaction: (Cytokine potency assay (cytokine INFgamma, JAK1/2, pSTAT1 in CD14+ monocyte cells)) EUB0000644a JAK1
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Inhibition of human recombinant c-RAF
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)c3F)CC2)C1
InChIKey: KTBSXLIQKWEBRB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 553.52, ALogP 3.6, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): CC[C@@H]1CN(C(=O)NCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
InChIKey: WYQFJHHDOKWSHR-MNOVXSKESA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Affinity Phenotypic Cellular interaction: (Cytokine potency assay (cytokine IL-4, JAK1/3, pSTAT6 in HEKa, human epithelial keratinocytes, adult cells)) EUB0000644a JAK1
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 380.37, ALogP 2.91, HBA 4, HBD 2, PSA 78.32, QED 0.73
Compound (SMILES): CN(C)CCCNC(=O)c1csc2nc(-c3ccc(NC(=O)Nc4cc(C(C)(C)C)on4)cc3)cn12
InChIKey: VBYMFAOTZHNONG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase Chk1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14757
Assay: Inhibition of human recombinant CHK1
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 509.64, ALogP 4.67, HBA 8, HBD 3, PSA 116.8, QED 0.3