lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(CNC[C@H]2CC[C@H](c3nnn4cnc5[nH]ccc5c34)CC2)s1
InChIKey: UXEHANJJLFQUIY-SHTZXODSSA-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.
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 380.52, ALogP 4.04, HBA 6, HBD 2, PSA 70.9, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H](O)CNCC(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NYYKCMGNIZNHAN-IBGZPJMESA-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 516.52, ALogP 3.7, HBA 9, HBD 2, PSA 97.56, QED 0.33
Compound (SMILES): CC(C)(O)CNC(=O)c1cc(NC(=O)c2cc(-c3ccccn3)c(Cl)cc2Cl)n(-c2ccccc2)n1
InChIKey: NXDRKVFQQJUBOG-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35739
Assay: Antagonist activity at TrkA in rat DRG assessed as inhibition of NGF-induced ERK phosphorylation preincubated for 60 mins followed by NGF addition and measured after 30 mins
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 524.41, ALogP 4.99, HBA 6, HBD 3, PSA 109.14, QED 0.32
Compound (SMILES): CNCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: FWUSQYKXFMDVPH-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 418.5, ALogP 3.41, HBA 8, HBD 1, PSA 77.33, QED 0.47
Compound (SMILES): COc1cc(OC)cc(N(CC(=O)NCCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: TZXHPCRUOAVQPR-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 462.51, ALogP 2.29, HBA 9, HBD 2, PSA 114.63, QED 0.39
Compound (SMILES): N=C(N)NCCCCC(=O)Nc1ccc(C[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)cc1
InChIKey: BLLLAUHTNAVSQR-VXKWHMMOSA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of integrin alphaVbeta1 (unknown origin)-mediated CHO cell adhesion to fibronectin preincubated for 15 to 30 mins followed by 60 min incubation for adhesion by crystal violet staining based cell adhesion assay
Measurement: IC50 = 0.63 nM (pChEMBL 9.199999809265137)
Descriptors: MW 558.66, ALogP 1.24, HBA 6, HBD 6, PSA 194.78, QED 0.12
Compound (SMILES): NC(=O)c1cc(-c2ccc(F)cc2)c2ccc(CN3C(=O)CCC3=O)cc2n1
InChIKey: XSTBUOHORFUCIB-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14832
Assay: Antagonist activity at mGluR3 (unknown origin) by FLIPR assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 377.38, ALogP 2.79, HBA 4, HBD 1, PSA 93.36, QED 0.71
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(F)cc(C(F)(F)F)c3)CC2)C1
InChIKey: XSVNQCQIBLRIMT-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 > 10 nM (pChEMBL 8)
Descriptors: MW 552.54, ALogP 4.21, HBA 7, HBD 1, PSA 106.73, QED 0.37
Compound (SMILES): COc1cc(OC)c(Cl)c(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: XLRXSFITRKMMRS-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 507.04, ALogP 5.32, HBA 8, HBD 0, PSA 68.54, QED 0.3
Compound (SMILES): N#Cc1cccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)c1
InChIKey: VDJRBBPYNWAREB-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 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 357.42, ALogP 2.86, HBA 6, HBD 1, PSA 85.9, QED 0.61
Compound (SMILES): COc1cc(OC)cc(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cnn(CCCN)c4)nc3c2)c1.Cl
InChIKey: GIBFLJLQDVDIAP-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 = 7244.36 nM (pChEMBL 5.139999866485596)
Descriptors: MW 543.59, ALogP 4.54, HBA 9, HBD 2, PSA 103.35, QED 0.24
Compound (SMILES): COCCN1CCN(c2ccc(Nc3nccc(-c4c(-c5cccc(C(=O)Nc6c(F)cccc6F)c5)nc5ccccn45)n3)c(OC)c2)CC1
InChIKey: DUMYPWASWOVLDF-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 690.75, ALogP 6.51, HBA 10, HBD 2, PSA 109.15, QED 0.16
Compound (SMILES): CO[C@]1(C(F)(F)F)CC[C@]2(CC1)NC(=O)C(c1cc(-c3ccc(Cl)c(F)c3)ccc1C)=C2O
InChIKey: YXQJEEBQFDIEBP-YHBQERECSA-N
Target: Acetyl-CoA carboxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O00763
Assay: Human ACC2 Enzyme Assay: For the assay, 50 nl of a 100-times concentrated solution of the test substance in DMSO were pipetted into a white low-volume 384-well microtitre plate (Greiner Bio-One, Frickenhausen, Germany), 2.5 μl of a solution of hACC2 in assay buffer [50 mM HEPES/NaOH pH 7.5, 2 mM MgCl2, 2 mM potassium citrate, 12 mM NaHCO3, 2 mM dithiothreitol (DTT), 0.005% (w/v) bovine serum albumin (BSA)] were added and the mixture was incubated for 15 min to allow prebinding of the substances to the enzyme prior to the enzyme reaction. The enzyme reaction was then started by addition of 2.5 μl of a solution of adenosine triphosphate (ATP, 100 μM=>final concentration in 5 μl of assay volume: 50 μM) and acetyl-CoA (20 μM=>final concentration in 5 μl assay volume: 10 μM) in assay buffer, and the resulting mixture was incubated at 22 °C. for the reaction time of 45 min. The concentration of the hACC2 was adjusted to the respective activity of the enzyme and set such that the assay was carried out in the linear range. Typical concentrations were in the range of 2 ng/μl. The reaction was stopped by addition of 2.5 μl of the "ADP-GLO reagent" (1:1.5-times diluted), and the resulting mixture was incubated at 22 °C. for 1 h to convert the unreacted ATP completely into cAMP. 2.5 μl of the "kinase detection reagent" were then added (1.2-times more concentrated than recommended by the manufacturer), the resulting mixture was incubated at 22 °C. for 1 h and the luminescence was then measured using a suitable measuring instrument (Viewlux or Topcount from Perkin-Elmer or Pherastar from BMG Labtechnologies).
Measurement: IC50 = 2010 nM (pChEMBL 5.699999809265137)
Descriptors: MW 483.89, ALogP 6.11, HBA 3, HBD 2, PSA 58.56, QED 0.52
Compound (SMILES): COc1ncccc1NC(=O)N1CCC(N2CC(CC#N)(n3ccc(-c4ncnc5[nH]ccc45)c3)C2)CC1
InChIKey: ZPSUVOGNAHWJDK-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 511.59, ALogP 3.45, HBA 8, HBD 2, PSA 127.99, QED 0.41
Compound (SMILES): N#CCC1(n2cc(-c3c(F)cnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)C3CCC(F)(F)CC3)CC2)C1
InChIKey: GYKTUKONDFVHDX-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 525.58, ALogP 4.31, HBA 6, HBD 1, PSA 93.84, QED 0.54
Compound (SMILES): CC(=O)OC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: HANZATNUZWTKEW-HAQNSBGRSA-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 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 313.36, ALogP 2.44, HBA 6, HBD 1, PSA 85.17, QED 0.75
Compound (SMILES): N#CCC1(n2cc(C(N)=O)c(Nc3ccnc(F)c3)n2)CCC(Nc2ccccn2)CC1
InChIKey: VJWMEQHGWFDKHM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Biochemical Assay: The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction and the plates were shaken and then incubated at room temperature for 120 minutes. At the end of the incubation, 20 uL of 2x stop buffer (streptavidin-Dylight 650 (Thermo #84547B/100 mL), Eu-tagged pY20 antibody (Perkin Elmer #AD0067), EDTA, HEPES, and Triton) was added to quench the reaction.
Measurement: IC50 = 195 nM (pChEMBL 6.710000038146973)
Descriptors: MW 434.48, ALogP 3.32, HBA 8, HBD 3, PSA 134.54, QED 0.49
Compound (SMILES): O=C(O)c1ccc(CC[C@H]2C(=O)CC[C@@H]2/C=C/C(O)Cc2ccc(F)cc2)cc1
InChIKey: TZVFTSQQDVXJEF-HPILLFOASA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Radioligand Binding Assay: The cell homogenate was centrifuged at 19000 r.p.m. for 20 min at 4° C. using a Beckman Ti-60 rotor. The resultant pellet was resuspended in TME buffer to give a final 1 mg/ml protein concentration, as determined by Biorad assay. Radioligand binding competition assays vs. [3H-]17-phenyl PGF2a , (5 nM) were performed in a 100 μl volume for 60 min. Binding reactions were started by adding plasma membrane fraction. The reaction was terminated by the addition of 4 ml ice-cold TRIS-HCl buffer and rapid filtration through glass fiber GF/B filters using a Brandel cell harvester. The filters were washed 3 times with ice-cold buffer and oven dried for one hour. [3H-] PGE2 (specific activity 180 Ci mmol) was used as the radioligand for EP receptors. [3H] 17-phenyl PGF2a, was employed for FP receptor binding studies. Binding studies employing EP1, EP2, EP4 and FP receptors were performed in duplicate in at least three separate experiments. A 200 μl assay volume was used. Incubations w
Measurement: Ki = 902 nM (pChEMBL 6.039999961853027)
Descriptors: MW 396.46, ALogP 4.21, HBA 3, HBD 2, PSA 74.6, QED 0.66
Compound (SMILES): Br.c1ccc2c(c1)CCN(CCCc1nc3ccccc3s1)C2
InChIKey: FWJIGGZKXTXJRN-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-mesulergine from human 5-HT2C receptor by liquid scintillation counting method
Measurement: Ki = 1182 nM (pChEMBL 5.929999828338623)
Descriptors: MW 308.45, ALogP 4.29, HBA 3, HBD 0, PSA 16.13, QED 0.71
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C(C)(C)C#Cc2nccc(OC)n2)c1
InChIKey: XNXPSFHVHIERHC-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 = 91.2 nM (pChEMBL 7.039999961853027)
Descriptors: MW 535.61, ALogP 4.81, HBA 10, HBD 0, PSA 100.31, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(CCn2ccnc2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: LAQISKDGTLGFIK-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 = 52.48 nM (pChEMBL 7.28000020980835)
Descriptors: MW 469.55, ALogP 4.39, HBA 9, HBD 0, PSA 83.12, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(Cc2cnccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QBQDRJRWFJDCET-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 453.51, ALogP 4.18, HBA 9, HBD 0, PSA 91.08, QED 0.36
Compound (SMILES): N#Cc1ccnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4cccnc4)c3F)c12
InChIKey: VJLBLADBINDMEV-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using MFC as substrate after 45 mins
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 439.4, ALogP 3.14, HBA 6, HBD 2, PSA 128.6, QED 0.46
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCNCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: UCZYIPRLKWCDDW-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 = 3.715 nM (pChEMBL 8.430000305175781)
Descriptors: MW 473.58, ALogP 3.09, HBA 9, HBD 1, PSA 80.57, QED 0.42
Compound (SMILES): FC(F)(F)c1ccc(CCN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: NIGMZMFZEBEOSJ-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 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 414.44, ALogP 4.05, HBA 5, HBD 1, PSA 62.11, QED 0.55
Compound (SMILES): C[C@H](O)CC(=O)N1CCC(c2nc(-c3cnc(N)c(-c4nnc(C(C)(C)C)o4)n3)n(C)n2)CC1
InChIKey: INFABNNEKSYVBX-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Mus musculus
UniProt: P42337
Assay: Cell Based Assay: This assay was used to measure PI3K-alpha inhibition in cells. BT474 cells (human breast ductal carcinoma, ATCC HTB-20) were seeded into black 384 well plates (Costar, #3712) at a density of 5600 cells/well in DMEM containing 10% FBS and 1% glutamine and allowed to adhere overnight.The following morning compounds in 100% DMSO were added to assay plates by acoustic dispensing. After a 2 hour incubation at 37 C. and 5% CO2, the medium was aspirated and the cells were lysed with a buffer containing 25 mM Tris, 3 mM EDTA, 3 mM EGTA, 50 mM sodium fluoride, 2 mM Sodium orthovanadate, 0.27M sucrose, 10 mM beta-glycerophosphate, 5 mM sodium pyrophosphate, 0.5% Triton X-100 and complete protease inhibitor cocktail tablets (Roche #04 693 116 001, used 1 tab per 50 ml lysis buffer).After 20 minutes, the cell lysates were transferred into ELISA plates (Greiner #781077) which had been pre-coated with an anti total-AKT antibody in PBS buffer.
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 469.55, ALogP 1.68, HBA 11, HBD 2, PSA 161.97, QED 0.56
Compound (SMILES): N#Cc1ccnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4c(F)cccc4F)c3F)c12
InChIKey: UPPPVANQFAMRRM-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using MFC as substrate after 45 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 474.39, ALogP 4.02, HBA 5, HBD 2, PSA 115.71, QED 0.33
Compound (SMILES): C1=C(CCN2CCc3ccccc3C2)Cc2ccccc21
InChIKey: CPTMQUFMCPDSBM-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D3 receptor by liquid scintillation counting method
Measurement: Ki = 89.13 nM (pChEMBL 7.050000190734863)
Descriptors: MW 275.39, ALogP 4.07, HBA 1, HBD 0, PSA 3.24, QED 0.82
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C(C)CNCC(F)(F)F)c1
InChIKey: JFHRSPHNHAHHOG-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 500.53, ALogP 4.73, HBA 8, HBD 1, PSA 77.33, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CCn2cnc(C)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: BEGHDVFYWWPCOW-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 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 470.54, ALogP 3.79, HBA 10, HBD 0, PSA 96.01, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCN)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1.Cl
InChIKey: DYBBAKRYVKNMJY-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human N-terminal His6-tagged FGFR3 expressed in insect Sf21 cells using Btn-Flt3 as substrate after 3 hrs by time resolved fluorescence assay
Measurement: IC50 = 1.514 nM (pChEMBL 8.819999694824219)
Descriptors: MW 434.5, ALogP 2.6, HBA 9, HBD 2, PSA 111.55, QED 0.41
Compound (SMILES): Nc1ncc(-c2ncccc2C(F)(F)F)nc1C(=O)Nc1ncccc1N1CCC(N)CC1
InChIKey: KYJCVYZGCYEQEA-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin)
Measurement: IC50 = 8700 nM (pChEMBL 5.059999942779541)
Descriptors: MW 458.45, ALogP 2.71, HBA 8, HBD 3, PSA 135.94, QED 0.54
Compound (SMILES): COc1ccc(OC)c(N(CCNC(C)C)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: FXBPODZDHNYGBT-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 = 154.88 nM (pChEMBL 6.809999942779541)
Descriptors: MW 432.53, ALogP 4.17, HBA 7, HBD 2, PSA 88.19, QED 0.41
Compound (SMILES): Cc1cc2ccc1[C@@H](C)COC(=O)Nc1ccc(S(=O)(=O)C3CC3)c(c1)CN(C)C(=O)[C@@H]2Nc1ccc2c(N)nccc2c1
InChIKey: DKEJQQLJGULWDZ-WENCNXQZSA-N
Target: Coagulation factor VII (SINGLE PROTEIN), Homo sapiens
UniProt: P08709
Assay: In Vitro Assay: Tissue kallikrein-1 (37° C) activity was determined in reactions containing 0.05 nM enzyme and 90 μM substrate (H-D-Val-Leu-Arg-AFC) in buffer (0.1M sodium phosphate pH 7.4, 0.2 M NaCl, 0.5% PEG 8000, and 1% DMSO). Assays were performed using 96-well microtiter plates (COSTAR 3600, CORNING, NY, USA) and a thermostatic temperature controlled plate reader (SPECTRAMAX® Gemini, Molecular Devices, Sunnyvale, Calif., USA). Fluorescence was monitored using 400 nm excitation and 505 nm emission wavelengths.
Measurement: Ki = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 613.74, ALogP 5.54, HBA 8, HBD 3, PSA 143.72, QED 0.27
Compound (SMILES): O=C(O)c1c[nH]c2cc(Cl)c(-c3ccc(C4(O)CCC4)cc3)cc12
InChIKey: FHQXLWCFSUSXBF-UHFFFAOYSA-N
Target: AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13131
Assay: Activation of recombinant human AMPK alpha1/beta1/gamma1 using Cy5-labelled SAMS as substrate in presence of ATP by TR-FRET assay
Measurement: EC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 341.79, ALogP 4.56, HBA 2, HBD 3, PSA 73.32, QED 0.65
Compound (SMILES): COc1cc(Nc2ccc(S(=O)(=O)NCC3CC3)c(C(F)(F)F)c2)cc(OC)c1
InChIKey: PXRZBSVMVTXTQV-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Binding Assay: The binding assays were performed by testing the ability of the new compounds to displace the radiolabeled synthetic non-selective cannabinoid agonist [3H]CP55940 (168 Ci/mmol; PerkinElmer) from the human CB1 (hCB1) or human CB2 (hCB2) receptors on membranes derived from stably transfected HEK-293 cells (PerkinElmer). Membranes were diluted in assay buffer (50 mM Tris-HCl, 1 mM EDTA, 1 mM MgCl2, 1 mg/ml BSA, pH=7.4). The amount of membrane was determined for each batch of membranes according to protein binding assay. The minimum amount of membrane that gave 50% specific binding was used for the binding assay. In most assays, binding was tested using 8 μg and 4 μg protein of hCB1 and hCB2 membranes, respectively. The tested compounds were dissolved in DMSO and diluted in assay buffer to a final concentration of 0.1% solvent. Total binding of [3H]CP55940 was evaluated with 1.5 nM to hCB1 and with 0.5 nM to hCB2, according to Kd affinity of [3H]CP55940 for the respective membranes. The ability of the tested compounds to displace [3H]CP55940 was evaluated first at a single concentration point of 100 nM for binding toward hCB2 or hCB1. In certain cases, the displacement was tested at compound concentrations ranging from 0.03 nM to 10 μM. Non-specific binding was measured by the addition of 1 μM of unlabelled CP55940 to the tubes. Binding assays were performed in triplicate in a total volume of 500 μl for 60 minutes at 30° C., in a shaking bath. Free and bound radioligands were separated by rapid filtration through GF/C filter plates (PerkinElmer) that had been presoaked with 0.1% Polyethylenimine (Sigma). Filters were shaken for 1 hour in 7 ml scintillation fluid (PerkinElmer) and radioactivity was determined by liquid scintillation counter (Wallac; PerkinElmer).
Measurement: Ki = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 430.45, ALogP 4.15, HBA 5, HBD 2, PSA 76.66, QED 0.66
Compound (SMILES): O=C1NN=C2CCCc3[nH]c4cccc1c4c32
InChIKey: GGJVOTFHPYZESL-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Enzymatic Assay: PARP-2 and PARP-3 enzymatic assays were conducted using commercial PARP-2/PARP-3 Chemiluminescent Assay Kit (BPS Biosciences) and the protocols with the kits. Briefly, histones were coated in a high binding plate first, and incubated with PARP-2 or PARP-3, and increasing concentrations of compounds for 0.5h. Then, biotinylated NAD and activated DNA were added to the wells. The biotinylated PARylation product was measured by adding streptavidin-HRP and HRP substrates which produce chemiluminescence. The IC50s were calculated based on residual enzyme activity in presence of increasing concentrations of compounds.
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 225.25, ALogP 1.95, HBA 2, HBD 2, PSA 57.25, QED 0.71
Compound (SMILES): COc1cc(-c2ccc3c(-c4cc5ccccc5[nH]4)n[nH]c3c2)ccc1O
InChIKey: YANIJISPXQRULY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of human GST-tagged CDK4/cyclin D1 expressed in Escherichia coli using retinoblastoma (386 to 928 residues) as substrate after 20 mins by gamma32P-ATP based scintillation counting analysis
Measurement: Ki = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 355.4, ALogP 5.09, HBA 3, HBD 3, PSA 73.93, QED 0.42
Compound (SMILES): CC(C)(C)c1ccc(N2C(=O)CC[C@@H]2COCc2ccc(C(=O)O)o2)cc1
InChIKey: BADIOVUTPYVHGM-MRXNPFEDSA-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 = 1921 nM (pChEMBL 5.71999979019165)
Descriptors: MW 371.43, ALogP 3.99, HBA 4, HBD 1, PSA 79.98, QED 0.83
Compound (SMILES): Cc1nn(C)c(C)c1-c1nc2c(N3CCN(Cc4cccnc4)CC3)c(Br)cnc2[nH]1
InChIKey: BMSHQZWQPJMOJN-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition Assays: Inhibition of CYP isozymes was determined using a mixture of probe substrates. The samples were incubated for 10 minutes followed by protein precipitation with methanol. The substrate metabolites in each sample were measured by LC/MS/MS using reverse-phase liquid chromatography and positive ion mode ESI with multiple reaction monitoring (MRM).
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 481.4, ALogP 3.45, HBA 7, HBD 1, PSA 78.76, QED 0.48
Compound (SMILES): CNCCN(c1cc(F)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: OJURKTZIXKTKOA-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 = 5.623 nM (pChEMBL 8.25)
Descriptors: MW 406.47, ALogP 3.54, HBA 7, HBD 1, PSA 68.1, QED 0.51
Compound (SMILES): COc1cc(OC)cc(N(CC2(OC)CCCNC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: PSPPDERBYPGSJF-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 488.59, ALogP 3.95, HBA 9, HBD 1, PSA 86.56, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CCF)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IWPIUSKMWHWQQF-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 = 2.754 nM (pChEMBL 8.5600004196167)
Descriptors: MW 407.45, ALogP 4.16, HBA 7, HBD 0, PSA 65.3, QED 0.46
Compound (SMILES): Cc1c(-c2c(F)cc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)cc2c(Cl)cccn2c1=O
InChIKey: MKZXRTJEMMVZLT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human Ramos B cells assessed as reduction in goat anti human IgM-stimulated calcium flux preincubated for 1 hr followed by goat anti human IgM addition and measured for 180 secs by FLIPR assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 571.01, ALogP 5.18, HBA 6, HBD 3, PSA 122.59, QED 0.27
Compound (SMILES): COc1cc(OCCO)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1.Cl
InChIKey: NTAJFSBXUQKVTI-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 = 11.48 nM (pChEMBL 7.940000057220459)
Descriptors: MW 475.55, ALogP 3.41, HBA 9, HBD 2, PSA 105.76, QED 0.34
Compound (SMILES): Cc1c(F)ccc2[nH]cc(C(=O)OCC34CCN(CC3)CC4)c12
InChIKey: MBXZXQXJYDODNK-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 316.38, ALogP 3.26, HBA 3, HBD 1, PSA 45.33, QED 0.88
Compound (SMILES): COc1cc(OC)cc(N(CC2CCN(CC(F)(F)F)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: LDRPTUAJCNQUAA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 134.9 nM (pChEMBL 6.869999885559082)
Descriptors: MW 540.59, ALogP 5.46, HBA 8, HBD 0, PSA 68.54, QED 0.29
Compound (SMILES): COc1cc(OC)cc(N(CC#CC2(O)CCOCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QNVUTZQLKFYKPS-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 = 16.6 nM (pChEMBL 7.78000020980835)
Descriptors: MW 499.57, ALogP 3.73, HBA 9, HBD 1, PSA 94.76, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CCCNC(=O)C(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: FFFJXBUHHHYLPP-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 = 1.096 nM (pChEMBL 8.960000038146973)
Descriptors: MW 514.51, ALogP 4.25, HBA 8, HBD 1, PSA 94.4, QED 0.33
Compound (SMILES): Cc1nc2ccc(-n3ncc(C(=O)c4cc5cc(CN6CCOCC6)ccc5[nH]4)c3N)cc2[nH]1
InChIKey: WRABCNDMFRHWIR-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells assessed as reduction in channel currents at -80 mV holding potential by automated whole-cell patch clamp method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 455.52, ALogP 3.18, HBA 7, HBD 3, PSA 117.85, QED 0.35
Compound (SMILES): Cc1ccc(CNC[C@H]2CC[C@H](c3nnn4cnc5[nH]ccc5c34)CC2)s1
InChIKey: UXEHANJJLFQUIY-SHTZXODSSA-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.
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 380.52, ALogP 4.04, HBA 6, HBD 2, PSA 70.9, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(C[C@@H](O)CNCC(F)(F)F)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NYYKCMGNIZNHAN-IBGZPJMESA-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 = 4.365 nM (pChEMBL 8.359999656677246)
Descriptors: MW 516.52, ALogP 3.7, HBA 9, HBD 2, PSA 97.56, QED 0.33
Compound (SMILES): CC(C)(O)CNC(=O)c1cc(NC(=O)c2cc(-c3ccccn3)c(Cl)cc2Cl)n(-c2ccccc2)n1
InChIKey: NXDRKVFQQJUBOG-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35739
Assay: Antagonist activity at unphosphorylated rat TrkA expressed in baculovirus expression system preincubated for 20 mins followed by TK-substrate-Biotin addition and measured after 35 mins by HTRF assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 524.41, ALogP 4.99, HBA 6, HBD 3, PSA 109.14, QED 0.32
Compound (SMILES): CNCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: FWUSQYKXFMDVPH-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 = 1.445 nM (pChEMBL 8.84000015258789)
Descriptors: MW 418.5, ALogP 3.41, HBA 8, HBD 1, PSA 77.33, QED 0.47
Compound (SMILES): COc1cc(OC)cc(N(CC(=O)NCCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: TZXHPCRUOAVQPR-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human N-terminal His6-tagged FGFR3 expressed in insect Sf21 cells using Btn-Flt3 as substrate after 3 hrs by time resolved fluorescence assay
Measurement: IC50 = 12.88 nM (pChEMBL 7.889999866485596)
Descriptors: MW 462.51, ALogP 2.29, HBA 9, HBD 2, PSA 114.63, QED 0.39
Compound (SMILES): N=C(N)NCCCCC(=O)Nc1ccc(C[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)cc1
InChIKey: BLLLAUHTNAVSQR-VXKWHMMOSA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of alphavbeta1 integrin (unknown origin) expressed in CHO cells assessed as inhibition of cell adhesion to fibronectin incubated for 60 mins by crystal violet staining based analysis
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 558.66, ALogP 1.24, HBA 6, HBD 6, PSA 194.78, QED 0.12
Compound (SMILES): NC(=O)c1cc(-c2ccc(F)cc2)c2ccc(CN3C(=O)CCC3=O)cc2n1
InChIKey: XSTBUOHORFUCIB-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14833
Assay: Antagonist activity at mGluR4 (unknown origin) by FLIPR assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 377.38, ALogP 2.79, HBA 4, HBD 1, PSA 93.36, QED 0.71
Compound (SMILES): COc1cc(OC)c(Cl)c(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: XLRXSFITRKMMRS-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 = 1.82 nM (pChEMBL 8.739999771118164)
Descriptors: MW 507.04, ALogP 5.32, HBA 8, HBD 0, PSA 68.54, QED 0.3
Compound (SMILES): N#Cc1cccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)c1
InChIKey: VDJRBBPYNWAREB-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 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 357.42, ALogP 2.86, HBA 6, HBD 1, PSA 85.9, QED 0.61
Compound (SMILES): COc1cc(OC)cc(N(CCCNCC(F)(F)F)c2ccc3ncc(-c4cnn(CCCN)c4)nc3c2)c1.Cl
InChIKey: GIBFLJLQDVDIAP-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 = 3.548 nM (pChEMBL 8.449999809265137)
Descriptors: MW 543.59, ALogP 4.54, HBA 9, HBD 2, PSA 103.35, QED 0.24
Compound (SMILES): CC(=O)OC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: HANZATNUZWTKEW-HAQNSBGRSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
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 = 880 nM (pChEMBL 6.059999942779541)
Descriptors: MW 313.36, ALogP 2.44, HBA 6, HBD 1, PSA 85.17, QED 0.75
Compound (SMILES): O=C(O)c1ccc(CC[C@H]2C(=O)CC[C@@H]2/C=C/C(O)Cc2ccc(F)cc2)cc1
InChIKey: TZVFTSQQDVXJEF-HPILLFOASA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Radioligand Binding Assay: The cell homogenate was centrifuged at 19000 r.p.m. for 20 min at 4° C. using a Beckman Ti-60 rotor. The resultant pellet was resuspended in TME buffer to give a final 1 mg/ml protein concentration, as determined by Biorad assay. Radioligand binding competition assays vs. [3H-]17-phenyl PGF2a , (5 nM) were performed in a 100 μl volume for 60 min. Binding reactions were started by adding plasma membrane fraction. The reaction was terminated by the addition of 4 ml ice-cold TRIS-HCl buffer and rapid filtration through glass fiber GF/B filters using a Brandel cell harvester. The filters were washed 3 times with ice-cold buffer and oven dried for one hour. [3H-] PGE2 (specific activity 180 Ci mmol) was used as the radioligand for EP receptors. [3H] 17-phenyl PGF2a, was employed for FP receptor binding studies. Binding studies employing EP1, EP2, EP4 and FP receptors were performed in duplicate in at least three separate experiments. A 200 μl assay volume was used. Incubations w
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 396.46, ALogP 4.21, HBA 3, HBD 2, PSA 74.6, QED 0.66
Compound (SMILES): Br.c1ccc2c(c1)CCN(CCCc1nc3ccccc3s1)C2
InChIKey: FWJIGGZKXTXJRN-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Displacement of [3H]-pyrilamine from human histamine H1 receptor by liquid scintillation counting method
Measurement: Ki = 822 nM (pChEMBL 6.079999923706055)
Descriptors: MW 308.45, ALogP 4.29, HBA 3, HBD 0, PSA 16.13, QED 0.71
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C(C)(C)C#Cc2nccc(OC)n2)c1
InChIKey: XNXPSFHVHIERHC-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 = 177.83 nM (pChEMBL 6.75)
Descriptors: MW 535.61, ALogP 4.81, HBA 10, HBD 0, PSA 100.31, QED 0.27
Compound (SMILES): COc1cc(OC)cc(N(CCn2ccnc2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: LAQISKDGTLGFIK-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 = 43.65 nM (pChEMBL 7.360000133514404)
Descriptors: MW 469.55, ALogP 4.39, HBA 9, HBD 0, PSA 83.12, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(Cc2cnccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QBQDRJRWFJDCET-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 = 2.138 nM (pChEMBL 8.670000076293945)
Descriptors: MW 453.51, ALogP 4.18, HBA 9, HBD 0, PSA 91.08, QED 0.36
Compound (SMILES): N#Cc1ccnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4cccnc4)c3F)c12
InChIKey: VJLBLADBINDMEV-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 439.4, ALogP 3.14, HBA 6, HBD 2, PSA 128.6, QED 0.46
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCNCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: UCZYIPRLKWCDDW-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 = 3.311 nM (pChEMBL 8.479999542236328)
Descriptors: MW 473.58, ALogP 3.09, HBA 9, HBD 1, PSA 80.57, QED 0.42
Compound (SMILES): C[C@H](O)CC(=O)N1CCC(c2nc(-c3cnc(N)c(-c4nnc(C(C)(C)C)o4)n3)n(C)n2)CC1
InChIKey: INFABNNEKSYVBX-LBPRGKRZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Mus musculus
UniProt: P42337
Assay: Cell Based Assay: This assay was used to measure PI3K-alpha inhibition in cells. BT474 cells (human breast ductal carcinoma, ATCC HTB-20) were seeded into black 384 well plates (Costar, #3712) at a density of 5600 cells/well in DMEM containing 10% FBS and 1% glutamine and allowed to adhere overnight.The following morning compounds in 100% DMSO were added to assay plates by acoustic dispensing. After a 2 hour incubation at 37 C. and 5% CO2, the medium was aspirated and the cells were lysed with a buffer containing 25 mM Tris, 3 mM EDTA, 3 mM EGTA, 50 mM sodium fluoride, 2 mM Sodium orthovanadate, 0.27M sucrose, 10 mM beta-glycerophosphate, 5 mM sodium pyrophosphate, 0.5% Triton X-100 and complete protease inhibitor cocktail tablets (Roche #04 693 116 001, used 1 tab per 50 ml lysis buffer).After 20 minutes, the cell lysates were transferred into ELISA plates (Greiner #781077) which had been pre-coated with an anti total-AKT antibody in PBS buffer.
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 469.55, ALogP 1.68, HBA 11, HBD 2, PSA 161.97, QED 0.56
Compound (SMILES): N#Cc1ccnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4c(F)cccc4F)c3F)c12
InChIKey: UPPPVANQFAMRRM-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 474.39, ALogP 4.02, HBA 5, HBD 2, PSA 115.71, QED 0.33
Compound (SMILES): C1=C(CCN2CCc3ccccc3C2)Cc2ccccc21
InChIKey: CPTMQUFMCPDSBM-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30729
Assay: Displacement of [3H]-N-methylspiperone from rat dopamine D4 receptor by liquid scintillation counting method
Measurement: Ki = 194.98 nM (pChEMBL 6.710000038146973)
Descriptors: MW 275.39, ALogP 4.07, HBA 1, HBD 0, PSA 3.24, QED 0.82