lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC(N)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PFFKWQNVRNBIGB-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 487.61, ALogP 3.61, HBA 9, HBD 1, PSA 94.56, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1.Cl
InChIKey: NDXCOBYSTJUJJD-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 474.61, ALogP 5.23, HBA 8, HBD 1, PSA 77.33, QED 0.34
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3F)ncnc2cc1OC[C@@H]1CN2CCOC[C@H]2CO1
InChIKey: ABXIBRWZRWHJCZ-KBPBESRZSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: Inhibition of recombinant human N-terminal GST-tagged factor 10a cleavage site-fused Flt1 (K784 to I1338 residues) expressed in baculovirus infected insect Sf9 cells using poly-EY as substrate after 120 mins in presence of gamma33P-ATP by liquid scintillation spectrometry
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 509.37, ALogP 4.31, HBA 8, HBD 1, PSA 77.97, QED 0.49
Compound (SMILES): Cc1ccc(OCCNc2nc(Nc3cc(C)[nH]n3)cc(C)c2C#N)cn1
InChIKey: BOWYXGHFMQMXPT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Fyn (SINGLE PROTEIN), Homo sapiens
UniProt: P06241
Assay: Inhibition of FYN (unknown origin)
Measurement: Ki = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 363.43, ALogP 3.23, HBA 7, HBD 3, PSA 111.54, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(CCNC[Si](C)(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: JMKXJKVYUUVONH-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 490.68
Compound (SMILES): Cc1c(-c2c(F)cc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)[nH]c2c(F)cc(F)cc2c1=O
InChIKey: WIJXOZNFPWXVAP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Jak2 Tyrosine Kinase Assay: The assays were performed in V-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2, 25 mM beta-glycerolphosphate, 0.015% Brij 35 surfactant and 4 mM DTT). The reaction was initiated by the combination of Jak2 tyrosine kinase with substrates and test compounds. The reaction mixture was incubated at room temperature for 60 minutes and terminated by adding 45 μL of 35 mM EDTA to each sample.
Measurement: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 572.54, ALogP 5.03, HBA 5, HBD 4, PSA 133.97, QED 0.24
Compound (SMILES): CS(=O)(=O)Nc1ccc(-c2nc3cc(NS(C)(=O)=O)ccc3o2)cc1
InChIKey: HGDCRMOPVMHNLX-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P54829
Assay: Inhibition of human PTPN5 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 381.44, ALogP 2.24, HBA 6, HBD 2, PSA 118.37, QED 0.7
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cncc(C(F)(F)F)n3)CC2)C1
InChIKey: VUMNCGMFRHJYTP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 536.52, ALogP 2.86, HBA 9, HBD 1, PSA 132.51, QED 0.41
Compound (SMILES): c1cc2c(ncn3nnc(C4CCN(Cc5csnn5)CC4)c23)[nH]1
InChIKey: SMPQVUVZVLHXCO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 340.42, ALogP 1.84, HBA 8, HBD 1, PSA 87.89, QED 0.61
Compound (SMILES): CC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N(C)CC(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)NC(C)(C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(N)=O)C(C)C)C(C)C
InChIKey: BSWBCDUBCHDFSM-YTMVHBNOSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Binding affinity to C-terminus 10x-His-taged human TFPI-1 (29 to 282 residues) incubated for 480 secs by SPR assay
Measurement: Kd = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 2358.73
Compound (SMILES): CCNCc1cc(C(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)nc(C(F)(F)F)n1
InChIKey: LNADOZPWRKKIOA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
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 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 593.62, ALogP 2.97, HBA 10, HBD 2, PSA 144.54, QED 0.32
Compound (SMILES): COc1cc(N2CCC(CCS(C)(=O)=O)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3cc(F)ccn23)n1
InChIKey: PGSWZQCCZKKHSP-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 785.85, ALogP 7.54, HBA 11, HBD 2, PSA 140.05, QED 0.13
Compound (SMILES): CCOc1cc(N2CCN(CCS(C)(=O)=O)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: NEVZWMZAOSTPNR-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 752.85, ALogP 6.3, HBA 11, HBD 2, PSA 134.06, QED 0.15
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)C3CCN(c4ncc(Cl)cc4F)CC3)CC2)C1
InChIKey: JNKOIMIJCLLCCZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 603.11, ALogP 3.84, HBA 9, HBD 1, PSA 122.86, QED 0.35
Compound (SMILES): COc1cn(C(C[C@H]2CC[C@H](OC)CC2)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: LARGKTWCHAEXEF-QDTYANCNSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition Assay: Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM Tris/HCl pH 7.4; 100 mM sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of plasma kallikrein from Kordia (0.6 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the substrate H-Pro-Phe-Arg-AMC dissolved in assay buffer (10 μl in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm).
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 564.04, ALogP 5.52, HBA 7, HBD 2, PSA 130.65, QED 0.35
Compound (SMILES): COC(=N)c1nc2ccc3ncnc(Nc4ccc(OC)cc4F)c3c2s1
InChIKey: RYBNARZBIXTFJS-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O43781
Assay: Inhibition of DYRK3 (unknown origin)
Measurement: IC50 = 21.1 nM (pChEMBL 7.679999828338623)
Descriptors: MW 383.41, ALogP 4.1, HBA 8, HBD 2, PSA 93.01, QED 0.41
Compound (SMILES): C[C@@H]1C[C@@H]2C[C@H](C1)C[C@@H](N1[C@@H]3CCC[C@H]1C[C@@H](n1c(=O)c(N4CC[C@H]4C(=O)O)nc4ccccc41)C3)C2
InChIKey: MAXKZGKDZCVVLT-VUOXEJBVSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: In Vitro Mu-Opioid Receptor Functional Assay: [35S]GTPγS functional assays were conducted using freshly thawed membranes expressing human μ-receptors. Assay reactions were prepared by sequentially adding the following reagents to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice (final concentrations indicated): membrane protein (0.026 mg/mL), saponin (10 mg/mL), GDP (3 mM) and [35S]GTPγS (0.20 nM; NEN). The prepared membrane solution (190 μL/well) was transferred to 96-shallow well polypropylene plates containing 10 μL of 20× concentrated stock solutions of the agonist DAMGO ([D-Ala2, N-methyl-Phe4 Gly-o15]-enkephalin) prepared in dimethyl sulfoxide (DMSO). Plates were incubated for 30 min at about 25 °C. with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GF/B filter plates (Packard, Meriden, Conn.) using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by three filtration washes with 200 μL of ice-cold wash buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at 50 °C. for 2-3 hr. BetaScint scintillation cocktail (Wallas, Turku, Finland) was added (50 μL/well) and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: EC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 504.68, ALogP 4.83, HBA 6, HBD 1, PSA 78.67, QED 0.64
Compound (SMILES): CCOc1cc(N2CCN(CCS(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3ccc(OCC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: IEQDZYFPBXQSDQ-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 810.93, ALogP 7, HBA 12, HBD 2, PSA 143.29, QED 0.12
Compound (SMILES): Cc1ncccc1-n1c([C@H](C)Nc2nc(N)nc(N)c2C#N)nc2cccc(Cl)c2c1=O
InChIKey: MODOHQQWQXQEQB-NSHDSACASA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of human full length PI3K p110alpha/p85alpha using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay
Measurement: IC50 = 6800 nM (pChEMBL 5.170000076293945)
Descriptors: MW 447.89, ALogP 2.74, HBA 10, HBD 3, PSA 161.42, QED 0.43
Compound (SMILES): CCOc1ccnc(C#CCN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)n1
InChIKey: PRVGMAOUBRLMGU-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 8709.64 nM (pChEMBL 5.059999942779541)
Descriptors: MW 521.58, ALogP 4.43, HBA 10, HBD 0, PSA 100.31, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(CC(=O)Nc2cc(O)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JMBVTEKOAZJGIC-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 511.54, ALogP 3.92, HBA 10, HBD 2, PSA 127.52, QED 0.32
Compound (SMILES): CS(=O)(=O)O.Cc1c(Cc2c(CO)nc3c(N)cc(N4CCOCC4)nn23)cccc1C(F)(F)F
InChIKey: IJKRASZDCNSORU-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta in human PC3 cells assessed as suppression of AKT phosphorylation at Ser473 after 60 mins by ELISA
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 421.42, ALogP 2.56, HBA 7, HBD 2, PSA 88.91, QED 0.67
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccn(C)c(=O)c1
InChIKey: JVGDBVAGMMZAGB-YKSBVNFPSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Activity at human muscarinic acetylcholine receptor M1 transfected in CHO-K1 cells assessed as intracellular calcium levels in presence of acetylcholine by FLIPR assay
Measurement: Ki = 302 nM (pChEMBL 6.519999980926514)
Descriptors: MW 503.59, ALogP 4.56, HBA 7, HBD 0, PSA 55.95, QED 0.35
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4cc5n(c4n3)C3(CCCCC3)CNC5=O)nc2)CC1
InChIKey: PDGKHKMBHVFCMG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: Inhibition of CDK6 (unknown origin) incubated for 60 mins in presence of ATP by plate reader based analysis
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 446.56, ALogP 2.72, HBA 8, HBD 2, PSA 91.21, QED 0.64
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4cccc(F)c4)ccc3o2)cc1)c1cccc(F)c1
InChIKey: JGAPJICEYAQHGJ-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of human PTPN2 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 32000 nM (pChEMBL 4.5)
Descriptors: MW 541.56, ALogP 5.37, HBA 6, HBD 2, PSA 118.37, QED 0.29
Compound (SMILES): COc1cc(N2CCC(N3CCN(S(C)(=O)=O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC(C)C)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: VUGSVMNPSQXIRQ-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 851.98, ALogP 7.07, HBA 12, HBD 2, PSA 146.53, QED 0.13
Compound (SMILES): COc1cc(OC)c(F)c(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1F
InChIKey: GLLVJFAKHOOPKT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.38 nM (pChEMBL 8.859999656677246)
Descriptors: MW 536.51, ALogP 5.01, HBA 8, HBD 1, PSA 77.33, QED 0.23
Compound (SMILES): O=C(Nc1ccc(F)cc1)N1N=C(c2ccncc2)CC1c1ccc(F)cc1
InChIKey: RDQXNTXNNZITKD-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of human T-type calcium channel Cav3.2 expressed in CHO cells assessed as inhibition of calcium tail current at -90 mV holding potential measured after 150 secs by QPatch assay
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 378.38, ALogP 4.74, HBA 3, HBD 1, PSA 57.59, QED 0.72
Compound (SMILES): COC/C(CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1)=N/O
InChIKey: YIDCCLXYFLNYHA-OGLMXYFKSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 7.943 nM (pChEMBL 8.100000381469727)
Descriptors: MW 462.51, ALogP 3.66, HBA 10, HBD 1, PSA 107.12, QED 0.23
Compound (SMILES): COc1ccc2[nH]cc(C(=O)OCC34CCN(CC3)CC4)c2c1OC
InChIKey: MHHANWALJYYOEO-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Cytochrome P450 Inhibition: Protocol 1: Studies were carried out in human liver microsomes. Human liver microsomes were purchased from BD Gentest. DMSO stocks were prepared for the test compounds. Aliquots of the DMSO solutions were diluted 1:3 by acetonitrile:ACN mixture (v/v: 40:60) to "400×" intermediate solutions, then further diluted by liver microsomes/buffer to "2×" intermediate solutions. "2×" intermediate solutions were mixed with "2×" NADPH/substrate solutions, which had been pre-warmed to 37° C. (final test compound concentrations were 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, 0.0136 μM, and 0 μM). The plates were kept in a 37° C. water bath for the duration of the experiment. At the end of incubation (5 minutes for 3A4; 45 minutes for 2C19; 10 minutes for 1A2, 2C9, 2D6), 120 μL of acetonitrile was added into corresponding wells. After the final time point was sampled, the plates were shaken at a vibrator (IKA, MTS 2/4) for 10 mM (600 rpm/min) and then centrifuged at 5594 g for 15 mM (Thermo Multifuge×3R). Aliquots of the supernatant were removed, diluted 1:1 into distilled water, and analyzed by LC-MS/MS. The peak area response ratio to internal standard (PARR) of the compounds at 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, and 0.0136 μM was compared to the PARR at 0 μM to determine the percent of metabolite generation from substrate at each test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 344.41, ALogP 2.83, HBA 5, HBD 1, PSA 63.79, QED 0.85
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1
InChIKey: MMGNRRUXETXMDE-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 4.786 nM (pChEMBL 8.319999694824219)
Descriptors: MW 447.54, ALogP 4.61, HBA 8, HBD 1, PSA 85.53, QED 0.4
Compound (SMILES): CCCCCC(O)c1ccc(N2C(=O)CC[C@@H]2COCc2ccc(C(=O)O)s2)cc1
InChIKey: NGKFLYGSJDSBQC-QSVWIEALSA-N
Target: Prostaglandin D2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q13258
Assay: Agonist activity at human recombinant DP receptor expressed in HEK293 cells assessed as effect on calcium accumulation by Fluo-4 AM dye based FLIPR assay
Measurement: EC50 = 3233 nM (pChEMBL 5.489999771118164)
Descriptors: MW 431.55, ALogP 4.77, HBA 5, HBD 2, PSA 87.07, QED 0.5
Compound (SMILES): Cc1ccc(CN2CC[C@@H](N3CC[C@@H](c4ccc(O)cc4)[C@H](F)C3)C2=O)cc1
InChIKey: UNVYDSCXINFREZ-BHDDXSALSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes
Measurement: IC50 > 18000 nM (pChEMBL 4.744999885559082)
Descriptors: MW 382.48, ALogP 3.63, HBA 3, HBD 1, PSA 43.78, QED 0.88
Compound (SMILES): COc1cc(OC)cc(N(CCCO)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: WPAMXPNNWJGKNP-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.399 nM (pChEMBL 8.619999885559082)
Descriptors: MW 449.51, ALogP 3.02, HBA 9, HBD 2, PSA 105.76, QED 0.38
Compound (SMILES): NC(=O)c1cccc(-c2c[nH]c3ncnc(N4CCOCC4)c23)c1
InChIKey: NCXSLSJEOUOJBB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13188
Assay: Displacement of K5 tracer from full length C-terminal NanoLuc fused human STK3 expressed in HEK293T cells incubated for 2 hrs by NanoBRET assay
Measurement: IC50 = 303 nM (pChEMBL 6.519999980926514)
Descriptors: MW 323.36, ALogP 1.56, HBA 5, HBD 2, PSA 97.13, QED 0.76
Compound (SMILES): COc1cc(OC)cc(N(CC2CCN(C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: BXMUZNHPFQUNSZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 4.898 nM (pChEMBL 8.3100004196167)
Descriptors: MW 472.59, ALogP 4.53, HBA 8, HBD 0, PSA 68.54, QED 0.39
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1c(-c2c(Cl)cccc2Cl)noc1C
InChIKey: AHIOWTSQFILAEW-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 576.27, ALogP 8.54, HBA 7, HBD 1, PSA 82.3, QED 0.21
Compound (SMILES): C[C@@H](c1nc2ccc(N3CCC[C@@H](C(=O)N4CCCC4)C3)nc2[nH]1)n1cc(Cl)cn1
InChIKey: NOSUIOGIJKVTAO-LSDHHAIUSA-N
Target: Diacylglycerol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PD7
Assay: Inhibition of human DGAT2
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 427.94, ALogP 3.26, HBA 6, HBD 1, PSA 82.94, QED 0.69
Compound (SMILES): O=C(c1c(F)ccc(NS(=O)(=O)c2cccnc2)c1F)c1c[nH]c2nccc(Cl)c12
InChIKey: UGHOYILAXQCULM-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin) using AMMC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 448.84, ALogP 3.92, HBA 5, HBD 2, PSA 104.81, QED 0.45
Compound (SMILES): CC(C(=O)Nc1ccc(C(=O)O)cc1)n1cc(Cl)c(-c2cc(Cl)ccc2C#N)cc1=O
InChIKey: MYLKJUSMRUADNT-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Measurement of FXIa Inhibition: To determine the factor XIa inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic factor XIa substrate to determine the enzymatic activity of human factor XIa. Here, factor XIa cleaves from the peptic factor XIa substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM of Tris/HCl pH 7.4; 100 mM of sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of factor XIa from Kordia (0.45 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the factor XIa substrate Boc-Glu(OBzl)-Ala-Arg-AMC dissolved in assay buffer (10 μM in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm). The measured emissions of the test batches with test substance are compared to those of control batches without test substance (only dimethyl sulphoxide instead of test substance in dimethyl sulphoxide), and the IC50 values are calculated from the concentration/activity relationships.
Measurement: IC50 = 275 nM (pChEMBL 6.559999942779541)
Descriptors: MW 456.29, ALogP 4.59, HBA 5, HBD 2, PSA 112.19, QED 0.58
Compound (SMILES): CCn1cc(-c2cnc3ccc(N(CCNC)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: ZNKBNXVWLPQHKJ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.455 nM (pChEMBL 8.609999656677246)
Descriptors: MW 432.53, ALogP 3.89, HBA 8, HBD 1, PSA 77.33, QED 0.43
Compound (SMILES): CNCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CCO)c3)nc2c1
InChIKey: CQDXYQFRLSRPQH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 7.079 nM (pChEMBL 8.149999618530273)
Descriptors: MW 448.53, ALogP 2.86, HBA 9, HBD 2, PSA 97.56, QED 0.38
Compound (SMILES): CCSC[C@@](O)([C@@H](Nc1cccc2nc(C)ccc12)c1ccc(OC)c(F)c1Cl)C(F)(F)F
InChIKey: NVBRVAKHESDYFE-FCHUYYIVSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Binding affinity to recombinant human androgen receptor expressed in baculovirus infected sf9 cells
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 502.96, ALogP 6.54, HBA 5, HBD 2, PSA 54.38, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCCNS(=O)(=O)N(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HONWIFHKRIBHLZ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal His6-tagged VEGFR2 (790 end residues) expressed in baculovirus infected insect Sf21 cells using Btn-Flt3 as substrate after 1 hr by time resolved fluorescence assay
Measurement: IC50 = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 525.64, ALogP 2.97, HBA 9, HBD 1, PSA 114.71, QED 0.3
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OC[C@@H]1CO[C@H]2[C@@H]1OC[C@@H]2OC
InChIKey: VENHPOQTVRCHJV-JXBRRONGSA-N
Target: Ephrin type-B receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54760
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 492.36, ALogP 4.5, HBA 8, HBD 1, PSA 83.96, QED 0.52
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3ccccn3)c2c(=O)n1-c1ccccc1
InChIKey: RYAQYDFEDXGXQC-FQEVSTJZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition Assays: Class I PI3-Ks can be either purchased (p110α/p85α, p110β/p85α, p110δ/p85α from Upstate, and p110γ from Sigma) or expressed as previously described (Knight et al., 2004). IC50 values are measured using either a standard TLC assay for lipid kinase activity (described below) or a high-throughput membrane capture assay. Kinase reactions are performed by preparing a reaction mixture containing kinase, inhibitor (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl2), and freshly sonicated phosphatidylinositol (100 μg/mL). Reactions are initiated by the addition of ATP containing 10 μCi of γ-32P-ATP to a final concentration of 10 or 100 μM and allowed to proceed for 5 minutes at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 μL 1N HCl followed by 160 μL CHCl3:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase is transferred to a new tube using a gel loading pipette tip precoated with CHCl3. This extract is spotted on TLC plates and developed for 3-4 hours in a 65:35 solution of n-propanol:1M acetic acid.
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 525.57, ALogP 3.9, HBA 8, HBD 2, PSA 120.2, QED 0.34
Compound (SMILES): O=C(c1ccc2cc(Oc3ccc(C(F)F)cn3)ccc2n1)N1CCNCC1
InChIKey: XJNLQAUECWCBNY-UHFFFAOYSA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Inhibition of human Nav1.8 by FRET based membrane potential assay
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 384.39, ALogP 3.41, HBA 5, HBD 1, PSA 67.35, QED 0.75
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ncccc2OC)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IHZFSYQVOKXLQL-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 48.98 nM (pChEMBL 7.309999942779541)
Descriptors: MW 506.57, ALogP 4.64, HBA 9, HBD 0, PSA 87.42, QED 0.3
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(C2CCCNC2)n1
InChIKey: HFTHZTJJBJKTGD-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 10500 nM (pChEMBL 4.980000019073486)
Descriptors: MW 516.45, ALogP 6.19, HBA 8, HBD 2, PSA 81.19, QED 0.3
Compound (SMILES): COc1ccc(NC(=O)C2=C(c3ccc(C)cc3)C[C@](c3ccc(OCCCC(F)(F)F)cc3)(C(F)(F)F)NC2=O)cc1
InChIKey: FBBPRPJENPWDPL-LJAQVGFWSA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q10469
Assay: Inhibition of human MGAT2 in mouse STC-1 cell based assay
Measurement: IC50 = 0.63 nM (pChEMBL 9.199999809265137)
Descriptors: MW 606.56, ALogP 7.09, HBA 4, HBD 2, PSA 76.66, QED 0.15
Compound (SMILES): Fc1cncc(-c2nc3ccc(F)cn3c2C2CC2)c1
InChIKey: VEYOJFZFZMQFIJ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of hepatic CYP3A4 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 271.27, ALogP 3.55, HBA 3, HBD 0, PSA 30.19, QED 0.71
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3sc(C(F)(F)F)cc3O)CC2)C1
InChIKey: ZBYPMXBGBCGFAB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 556.57, ALogP 3.84, HBA 9, HBD 2, PSA 126.96, QED 0.38
Compound (SMILES): COc1cc(O)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ZXPUNZSPQJIHJB-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.512 nM (pChEMBL 8.600000381469727)
Descriptors: MW 432.53, ALogP 3.88, HBA 8, HBD 2, PSA 88.33, QED 0.44
Compound (SMILES): CCN(C)Cc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PVNKKQPQLLGLMA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 456.59, ALogP 5.04, HBA 7, HBD 0, PSA 59.31, QED 0.35
Compound (SMILES): N=C(N)Nc1cccc(C(=O)Nc2ccc(C[C@H](NC(=O)[C@@H]3CCCN3S(=O)(=O)c3ccccc3)C(=O)O)cc2)c1
InChIKey: KXYAXQVLPNBUFO-ZEQRLZLVSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Cell Adhesion Assay : A panel of cell lines and integrin ligands were developed to allow rapid examination of potency and specificity of inhibitors against all 8 integrins that recognize RGD sequences in ligands. A subset of these was used to generate the very encouraging data about 8 shown above. These cell lines were used to calculate IC50 concentrations for each inhibitor synthesized to rapidly generate structure activity information to drive subsequent modification and synthesis. Inhibitors were evaluated for showing better potency/selectivity in CCl4-induced liver fibrosis.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 578.65, ALogP 2.21, HBA 6, HBD 6, PSA 194.78, QED 0.16
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC(N)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PFFKWQNVRNBIGB-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 5.888 nM (pChEMBL 8.229999542236328)
Descriptors: MW 487.61, ALogP 3.61, HBA 9, HBD 1, PSA 94.56, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C(C)C)c4)nc3c2)c1.Cl
InChIKey: NDXCOBYSTJUJJD-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.738 nM (pChEMBL 8.760000228881836)
Descriptors: MW 474.61, ALogP 5.23, HBA 8, HBD 1, PSA 77.33, QED 0.34
Compound (SMILES): Cc1ccc(OCCNc2nc(Nc3cc(C)[nH]n3)cc(C)c2C#N)cn1
InChIKey: BOWYXGHFMQMXPT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of KDR (unknown origin)
Measurement: Ki = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 363.43, ALogP 3.23, HBA 7, HBD 3, PSA 111.54, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(CCNC[Si](C)(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: JMKXJKVYUUVONH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 7.244 nM (pChEMBL 8.140000343322754)
Descriptors: MW 490.68
Compound (SMILES): c1cc2c(ncn3nnc(C4CCN(Cc5csnn5)CC4)c23)[nH]1
InChIKey: SMPQVUVZVLHXCO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 340.42, ALogP 1.84, HBA 8, HBD 1, PSA 87.89, QED 0.61
Compound (SMILES): COc1cn(C(C[C@H]2CC[C@H](OC)CC2)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: LARGKTWCHAEXEF-QDTYANCNSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition Assay: Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM Tris/HCl pH 7.4; 100 mM sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of plasma kallikrein from Kordia (0.6 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the substrate H-Pro-Phe-Arg-AMC dissolved in assay buffer (10 μl in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm).
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 564.04, ALogP 5.52, HBA 7, HBD 2, PSA 130.65, QED 0.35
Compound (SMILES): COC(=N)c1nc2ccc3ncnc(Nc4ccc(OC)cc4F)c3c2s1
InChIKey: RYBNARZBIXTFJS-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR20
Assay: Inhibition of DYRK4 (unknown origin)
Measurement: IC50 = 1570 nM (pChEMBL 5.800000190734863)
Descriptors: MW 383.41, ALogP 4.1, HBA 8, HBD 2, PSA 93.01, QED 0.41
Compound (SMILES): C[C@@H]1C[C@@H]2C[C@H](C1)C[C@@H](N1[C@@H]3CCC[C@H]1C[C@@H](n1c(=O)c(N4CC[C@H]4C(=O)O)nc4ccccc41)C3)C2
InChIKey: MAXKZGKDZCVVLT-VUOXEJBVSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: In Vitro Kappa-Opioid Receptor Functional Assay: Kappa opioid receptor membrane solution was prepared by sequentially adding final concentrations of 0.026 μg/μL kappa membrane protein (in-house), 10 μg/mL saponin, 3 μM GDP and 0.20 nM [35S]GTPγS to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice. The prepared membrane solution (190 μL/well) was transferred to 96-shallow well polypropylene plates containing 10 μL of 20× concentrated stock solutions of agonist prepared in DMSO. Plates were incubated for 30 min at a temperature of about 25 °C. with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GF/B filter plates (Packard) using a 96-well tissue harvester (Packard) and followed by three filtration washes with 200 μL ice-cold binding buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at 50 °C. for 2-3 hours. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: EC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 504.68, ALogP 4.83, HBA 6, HBD 1, PSA 78.67, QED 0.64
Compound (SMILES): Cc1ncccc1-n1c([C@H](C)Nc2nc(N)nc(N)c2C#N)nc2cccc(Cl)c2c1=O
InChIKey: MODOHQQWQXQEQB-NSHDSACASA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human full-length N-terminal His-tagged PI3K p110beta/p85alpha using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 447.89, ALogP 2.74, HBA 10, HBD 3, PSA 161.42, QED 0.43
Compound (SMILES): CCOc1ccnc(C#CCN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)n1
InChIKey: PRVGMAOUBRLMGU-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 6.918 nM (pChEMBL 8.15999984741211)
Descriptors: MW 521.58, ALogP 4.43, HBA 10, HBD 0, PSA 100.31, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(CC(=O)Nc2cc(O)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: JMBVTEKOAZJGIC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human FGFR1 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 1.549 nM (pChEMBL 8.8100004196167)
Descriptors: MW 511.54, ALogP 3.92, HBA 10, HBD 2, PSA 127.52, QED 0.32
Compound (SMILES): CS(=O)(=O)O.Cc1c(Cc2c(CO)nc3c(N)cc(N4CCOCC4)nn23)cccc1C(F)(F)F
InChIKey: IJKRASZDCNSORU-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta in human PC3 cells assessed as suppression of AKT phosphorylation at Thr308 after 60 mins by ELISA
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 421.42, ALogP 2.56, HBA 7, HBD 2, PSA 88.91, QED 0.67
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccn(C)c(=O)c1
InChIKey: JVGDBVAGMMZAGB-YKSBVNFPSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Activity at human muscarinic acetylcholine receptor M3 transfected in CHO-K1 cells assessed as intracellular calcium levels in presence of acetylcholine by FLIPR assay
Measurement: Ki = 354.81 nM (pChEMBL 6.449999809265137)
Descriptors: MW 503.59, ALogP 4.56, HBA 7, HBD 0, PSA 55.95, QED 0.35
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc4cc5n(c4n3)C3(CCCCC3)CNC5=O)nc2)CC1
InChIKey: PDGKHKMBHVFCMG-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of human CDK6/cyclin D3
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 446.56, ALogP 2.72, HBA 8, HBD 2, PSA 91.21, QED 0.64
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4cccc(F)c4)ccc3o2)cc1)c1cccc(F)c1
InChIKey: JGAPJICEYAQHGJ-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P54829
Assay: Inhibition of human PTPN5 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 31000 nM (pChEMBL 4.510000228881836)
Descriptors: MW 541.56, ALogP 5.37, HBA 6, HBD 2, PSA 118.37, QED 0.29
Compound (SMILES): COc1cc(OC)c(F)c(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1F
InChIKey: GLLVJFAKHOOPKT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.951 nM (pChEMBL 8.529999732971191)
Descriptors: MW 536.51, ALogP 5.01, HBA 8, HBD 1, PSA 77.33, QED 0.23
Compound (SMILES): O=C(Nc1ccc(F)cc1)N1N=C(c2ccncc2)CC1c1ccc(F)cc1
InChIKey: RDQXNTXNNZITKD-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1I (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P0X4
Assay: Inhibition of T-type calcium channel Cav3.3 (unknown origin) expressed in HEK293 cells assessed as calcium influx by Fluo-4-AM dye-based FLIPR assay
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 378.38, ALogP 4.74, HBA 3, HBD 1, PSA 57.59, QED 0.72
Compound (SMILES): COC/C(CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1)=N/O
InChIKey: YIDCCLXYFLNYHA-OGLMXYFKSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 6.026 nM (pChEMBL 8.220000267028809)
Descriptors: MW 462.51, ALogP 3.66, HBA 10, HBD 1, PSA 107.12, QED 0.23