lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cn(C(CC2CCC(O)CC2)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: CJNBXUGWBBVSDD-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 = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 550.01, ALogP 4.87, HBA 7, HBD 3, PSA 141.65, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CCC(=O)N(C)OC)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YZFIDVOGSPMNRW-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.951 nM (pChEMBL 8.529999732971191)
Descriptors: MW 476.54, ALogP 3.6, HBA 9, HBD 0, PSA 94.84, QED 0.34
Compound (SMILES): COc1ccnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4cccc(F)c4)c3F)c12
InChIKey: OUAKMJJSVVASQF-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BQ as substrate after 30 mins
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 461.42, ALogP 4.02, HBA 5, HBD 2, PSA 101.15, QED 0.42
Compound (SMILES): COc1ccc(Cl)c(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PNXHAMDNXPTINS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of TEL-fused FGFR3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 72 hrs by Alamar blue assay
Measurement: IC50 = 12.02 nM (pChEMBL 7.920000076293945)
Descriptors: MW 409.88, ALogP 3.82, HBA 7, HBD 1, PSA 76.3, QED 0.52
Compound (SMILES): COc1cc(OC)cc(N(CC2(CNC(C)C)COC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: FIOAXDHVMFVFQO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 14.45 nM (pChEMBL 7.840000152587891)
Descriptors: MW 502.62, ALogP 4.2, HBA 9, HBD 1, PSA 86.56, QED 0.35
Compound (SMILES): O=C(CCNC(=O)c1ccc(Cl)s1)Nc1ccc(N2CCOCC2=O)cc1
InChIKey: ZAKACSMWGGBPNE-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Biochemical assay using fluorogenic peptide substrate.Step 1: Compound transfer to plate (50 nl).Step 2: Dilute FXa in Assay Buffer.Step 3: Dilute substrate in Assay Buffer.Step 4: Add equal volumes to Assay plate (total assay volume 10 uL).Step 5: Centrifuge plate, 1 min, 1000 rpm.Step 6: Detect fluorescence signal: ex: 320 nm; Em. 405 nm (EnVision), every 10 min. 60 min pre-incubation of enzyme with compound and 15 min reaction time after substrate addition.
Measurement: IC50 = 5.75 nM (pChEMBL 8.239999771118164)
Descriptors: MW 407.88, ALogP 2.52, HBA 5, HBD 2, PSA 87.74, QED 0.77
Compound (SMILES): COc1cc(OC(C)C)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: XIUDTKCWPZRTTG-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 309.03 nM (pChEMBL 6.510000228881836)
Descriptors: MW 443.55, ALogP 5.37, HBA 7, HBD 0, PSA 65.3, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC[C@@H]2CO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MJBNLVZGJYYOOP-OAQYLSRUSA-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 = 1.778 nM (pChEMBL 8.75)
Descriptors: MW 488.59, ALogP 3.64, HBA 9, HBD 1, PSA 88.77, QED 0.38
Compound (SMILES): N#Cc1ccc2nnc(C(=O)N3CCC(c4cccc(F)c4C(F)(F)F)CC3)n2c1
InChIKey: TZIIUZZREBUIBM-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant human CYP2C19 expressed in insect cell microsomes in presence of NADPH-regenerating system after 15 to 45 mins by fluorescence probe substrate-based assay
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 417.37, ALogP 3.78, HBA 5, HBD 0, PSA 74.29, QED 0.6
Compound (SMILES): Cc1nc2c(N)cc(N3CCOCC3)nn2c1Nc1cccc(C(F)(F)F)c1CN1CC(O)C1
InChIKey: XHADQZSGBXAFFU-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 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 477.49, ALogP 2.4, HBA 9, HBD 3, PSA 104.18, QED 0.51
Compound (SMILES): Cc1ncc(F)cc1C1CCCN1c1ccn2ncc(C(=O)NC3CCC(O)CC3)c2n1
InChIKey: FDBFUEIJFKHRQU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: Compounds of Formula I were screened for their ability to inhibit Jak3 using the general enzyme inhibition assay method, in which the assay mixture contained 500 μM ATP, 10 μM Omnia Y7 peptide (Catalog # IVGN KNZ3071C, Invitrogen Corporation, Carlsbad, Calif.) and 1.5 nM Jak3 in a total volume of 20 μL. GST-tagged human Jak3 kinase domain comprising amino acids 781-1124 was purchased from Invitrogen Corporation, Carlsbad, Calif. (catalog # IVGN PV3855).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 438.51, ALogP 2.95, HBA 7, HBD 2, PSA 95.65, QED 0.65
Compound (SMILES): CCCCC[C@H](O)/C=C/[C@H]1CC(F)(F)C(=O)N1CCCCCCC(=O)O
InChIKey: PWZMQIUUWBQDQW-WFPWZJHXSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: cAMP Assay: 1. Seed cells on an EP2 or EP4 STEP plate at a density of 40,000-80,000 cells/well in 200 uL of reduced serum medium containing 0.5% FBS. Place the plate in a 37° C. incubator with 5% CO2 and incubate overnight. 2. After 16-18 hours of incubation, aspirate the culture media from each well. 3. Add 200 ul of culture medium containing 500 uM IBMX (an inhibitor of cAMP phosphodiesterase) and different concentration of test compounds to the assigned wells. For each test compound, at least 8 concentrations starting at highest 10 M and lowest 0.01 pM were tested. In addition each concentration had triplicates. A PGE2 curve (concentrations from lowest to highest, 0 pM, 0.384 pM, 1.92 pM, 9.6 pM, 48 pM, 240 pM, 1200 pM, and 6000 pM) was always run in parallel with test compounds. 4. Incubate the cells in a cell culture incubator for 30 minutes. 5. Centrifuge the plate at 1,000x rpm for 10 minutes. 6. Aspirate the supernatant.
Measurement: EC50 = 0.37 nM (pChEMBL 9.430000305175781)
Descriptors: MW 375.46, ALogP 3.76, HBA 3, HBD 2, PSA 77.84, QED 0.38
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCCc4cccc(OC)c43)s2)cc1
InChIKey: VJVDLRVFJTVWEO-QFIPXVFZSA-N
Target: RXR alpha/PPAR gamma (PROTEIN COMPLEX), Homo sapiens
UniProt: P19793
Assay: Agonist activity at human CMV-fused PPARgamma LBD/RXRalpha (unknown origin) expressed in African green monkey CV1 cells transfected with luciferase plasmid measured after 24 hrs by luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 475.61, ALogP 5.87, HBA 5, HBD 1, PSA 59, QED 0.39
Compound (SMILES): C[C@@H]1c2ncn(-c3ccccn3)c2CCN1C(=O)c1cccc(C(F)(F)F)c1Cl
InChIKey: OGZKVSNRBCPRRL-GFCCVEGCSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]astemizole from human ERG expressed in HEK293 cells by competitive binding assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 420.82, ALogP 4.7, HBA 4, HBD 0, PSA 51.02, QED 0.6
Compound (SMILES): COc1ccc(-c2cc(C(N)=O)nc3cc(CCc4cnc(C)nc4)ccc23)c(F)c1
InChIKey: YFISEEHEDYLAHH-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: O00222
Assay: Binding affinity to mGluR8 (unknown origin) by FLIPR assay
Measurement: IC50 = 26670 nM (pChEMBL 4.570000171661377)
Descriptors: MW 416.46, ALogP 4.03, HBA 5, HBD 1, PSA 90.99, QED 0.51
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: FMWDLYTVSRVYQS-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 = 28.18 nM (pChEMBL 7.550000190734863)
Descriptors: MW 445.52, ALogP 4.05, HBA 8, HBD 1, PSA 85.53, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cccc(C#N)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WHVXBHTZGZQBQC-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 = 43.65 nM (pChEMBL 7.360000133514404)
Descriptors: MW 501.55, ALogP 4.5, HBA 9, HBD 0, PSA 101.98, QED 0.31
Compound (SMILES): CC(C)[C@H](Cc1ccc(C(F)(F)F)cc1)C(=O)NC[C@@]1(C2CC2)NC(=O)NC1=O
InChIKey: VXXYNKXMRXANKX-KXBFYZLASA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: In Vitro Fluorescence Assay: A continuous assay is used in which the substrate is a synthetic peptide containing a fluorescent group (7-methoxycoumarin, Mca), which is quenched by energy transfer to a 2,4-dinitrophenyl group. The substrate is the peptide Mca-PQGL-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-AR-OH. When the peptide is cleaved by MMP a large increase in fluorescence is observed. The source of the enzyme for this assay is full-length, recombinant, human pro-MMP-2 expressed in Chinese Hamster Ovary (CHO) cells that is subsequently activated by an organomercurial compound, 4-aminophenyl mercuric acetate (APMA). APMA is removed through a desalting column (MMP-2 Calbiochem catalog number PF023). The assay buffer consists of 100 mM Tris-HCl (pH 7.5), 100 mM NaCl, 10 mM CaCl2 and 10 uM human serum albumin Each well of the 96-well plates consists of a 100 uL reaction mixture consisting of assay buffer, MMP (final concentration of 0.2 nM, prepared by diluting in assay buffer).
Measurement: IC50 = 3365 nM (pChEMBL 5.46999979019165)
Descriptors: MW 411.42, ALogP 2.62, HBA 3, HBD 3, PSA 87.3, QED 0.6
Compound (SMILES): O=C(NCc1cccc(N2CCN(C(=O)Cc3n[nH]c(=O)[nH]3)CC2)c1)c1nc2ccccc2c(=O)[nH]1
InChIKey: FMEMUXYNXWETSE-UHFFFAOYSA-N
Target: Matrilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P09237
Assay: Inhibition of recombinant human AMPA-activated MMP7 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 488.51, ALogP 0.16, HBA 7, HBD 4, PSA 159.94, QED 0.3
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC[C@@]3(C[C@H]3c3ccc(C(F)(F)F)cc3F)C2)n1C
InChIKey: ZIQDGXNDXRMRPM-HTAPYJJXSA-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 = 323.59 nM (pChEMBL 6.489999771118164)
Descriptors: MW 495.55, ALogP 5.3, HBA 7, HBD 0, PSA 59.98, QED 0.25
Compound (SMILES): CCOC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC(C4CC4)C4CC4)nc(Cl)nc31)[C@H](O)[C@@H]2O
InChIKey: IRHYVDDJDDMRKD-QNEDUEMWSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [125I]N6-(4-amino-3-iodobenzyl)adenosine-5-N-methyluronamide from human A3A adenosine receptor expressed in CHO cell membranes after 60 mins by scintillation proximity assay
Measurement: Ki = 236 nM (pChEMBL 6.630000114440918)
Descriptors: MW 447.92, ALogP 1.93, HBA 9, HBD 3, PSA 122.39, QED 0.43
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1.Cl
InChIKey: SUGJLIOPCUJKNU-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 = 5.248 nM (pChEMBL 8.279999732971191)
Descriptors: MW 502.62, ALogP 4.13, HBA 9, HBD 1, PSA 88.77, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CCCC#N)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WAHZMINPROSVEH-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 = 9.772 nM (pChEMBL 8.010000228881836)
Descriptors: MW 428.5, ALogP 4.49, HBA 8, HBD 0, PSA 89.09, QED 0.38
Compound (SMILES): [2H]C([2H])([2H])Oc1cc(F)cc(N(CCN)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: AJGWZFROWJUKON-BMSJAHLVSA-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 = 41.69 nM (pChEMBL 7.380000114440918)
Descriptors: MW 392.44, ALogP 3.27, HBA 7, HBD 1, PSA 82.09, QED 0.54
Compound (SMILES): C[C@H](NC(=O)c1c(N)nn2cccnc12)c1cc2cccc(C#Cc3ccncc3)c2c(=O)n1-c1ccccc1
InChIKey: MFRGEOCULIALIZ-FQEVSTJZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: PI3K-gamma Selective Assay: A compound's ability in selectively inhibiting PI3K-γ can be assessed using RAW264.7 macrophages. Briefly, serum-starved RAW264.7 cells are stimulated with a known GPCR agonist C5a. See, e.g., Camps et al., Nature Medicine (2005) 11(9):936-943. Cells can be treated with test compounds prior to, simultaneously with, or subsequent to the stimulation by C5a. RAW 264.7 cells respond to the complement component fragment C5a through activation of the C5a receptor, and the C5a receptor activates macrophages and induces cell migration. Test compounds' ability to inhibit C5a-mediated AKT phosphorylation is indicative of selective inhibition of PI3K-γ. Thus, by monitoring the reduction of phospho-AKT in stimulated RAW 264.7 cells (using for example, phospho-AKT antibodies), a compound's potential efficacy in selectively inhibiting PI3Kγ can be assessed.
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 525.57, ALogP 3.9, HBA 8, HBD 2, PSA 120.2, QED 0.34
Compound (SMILES): O=C(CN1CC(O)C(NC(=O)c2ccc(Cl)s2)C1)Nc1ccc(-n2ccccc2=O)cc1F
InChIKey: ARAVOODWJJJNBY-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Biochemical assay using fluorogenic peptide substrate.Step 1: Compound transfer to plate (50 nl).Step 2: Dilute FXa in Assay Buffer.Step 3: Dilute substrate in Assay Buffer.Step 4: Add equal volumes to Assay plate (total assay volume 10 uL).Step 5: Centrifuge plate, 1 min, 1000 rpm.Step 6: Detect fluorescence signal: ex: 320 nm; Em. 405 nm (EnVision), every 10 min. 60 min pre-incubation of enzyme with compound and 30 min reaction time after substrate addition.
Measurement: IC50 = 1.25 nM (pChEMBL 8.899999618530273)
Descriptors: MW 490.94, ALogP 2.11, HBA 7, HBD 3, PSA 103.67, QED 0.49
Compound (SMILES): COc1cc(OC)cc(N(C/C(C)=N/O)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RBVQYTAEUBJSEY-JFLMPSFJSA-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 = 25.7 nM (pChEMBL 7.590000152587891)
Descriptors: MW 432.48, ALogP 4.04, HBA 9, HBD 1, PSA 97.89, QED 0.27
Compound (SMILES): O=[N+]([O-])c1ccc(S(=O)(=O)Nc2ccc(-c3nc4cc(NS(=O)(=O)c5ccc([N+](=O)[O-])cc5)ccc4o3)cc2)cc1
InChIKey: SZJCSSKMAZDKFQ-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 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 595.57, ALogP 4.91, HBA 10, HBD 2, PSA 204.65, QED 0.17
Compound (SMILES): CCCCSc1nc2c(c(=O)n1-c1ccccc1)SCC2
InChIKey: RFJZKWIAOIBWJA-UHFFFAOYSA-N
Target: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (SINGLE PROTEIN), Homo sapiens
UniProt: O76083
Assay: In Vitro Enzyme Assay: In vitro enzyme assays were conducted via the Ba(OH)2 precipitation method of Wang et al. (32) using recombinant human PDE11A4, PDE10A1, PDE5A1, PDE6C, PDE8A (BPS Bioscience Inc.), PDE7A (BIOMOL International), and PDE4A10 enzymes (gift from HengmingKe), in the presence of 100 nM cGMP, 30 nM cAMP, 500 nM cGMP, 1.7 μM cGMP, 10 nM cAMP, 15 nM cAMP, and 625 nM cAMP, respectively. Inhibitor concentrations that reduce enzyme activity by 50% (IC50) are presented. The values are means of at least three independent experiments.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 318.47, ALogP 3.77, HBA 5, HBD 0, PSA 34.89, QED 0.48
Compound (SMILES): COc1ccc(C#CCN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)nc1
InChIKey: OXSXREVSJHOBMS-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 = 537.03 nM (pChEMBL 6.269999980926514)
Descriptors: MW 506.57, ALogP 4.64, HBA 9, HBD 0, PSA 87.42, QED 0.3
Compound (SMILES): COc1cc(OC)cc(N(CC2CCOCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: UZVFQJWFEJNXPR-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 = 32.36 nM (pChEMBL 7.489999771118164)
Descriptors: MW 459.55, ALogP 4.61, HBA 8, HBD 0, PSA 74.53, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCN)c4)nc3c2)c1
InChIKey: ZLIXAXDZDFQVBX-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 = 8.128 nM (pChEMBL 8.09000015258789)
Descriptors: MW 444.54, ALogP 4.02, HBA 8, HBD 1, PSA 91.32, QED 0.42
Compound (SMILES): COc1cn(C(CC2CCC(O)CC2)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: CJNBXUGWBBVSDD-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 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 550.01, ALogP 4.87, HBA 7, HBD 3, PSA 141.65, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CCC(=O)N(C)OC)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YZFIDVOGSPMNRW-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 = 15.49 nM (pChEMBL 7.809999942779541)
Descriptors: MW 476.54, ALogP 3.6, HBA 9, HBD 0, PSA 94.84, QED 0.34
Compound (SMILES): COc1ccc(Cl)c(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PNXHAMDNXPTINS-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 = 12.3 nM (pChEMBL 7.909999847412109)
Descriptors: MW 409.88, ALogP 3.82, HBA 7, HBD 1, PSA 76.3, QED 0.52
Compound (SMILES): COc1cc(OC)cc(N(CC2(CNC(C)C)COC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: FIOAXDHVMFVFQO-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 = 114.82 nM (pChEMBL 6.940000057220459)
Descriptors: MW 502.62, ALogP 4.2, HBA 9, HBD 1, PSA 86.56, QED 0.35
Compound (SMILES): O=C(CCNC(=O)c1ccc(Cl)s1)Nc1ccc(N2CCOCC2=O)cc1
InChIKey: ZAKACSMWGGBPNE-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Biochemical assay using fluorogenic peptide substrate.Step 1: Compound transfer to plate (50 nl).Step 2: Dilute FXa in Assay Buffer.Step 3: Dilute substrate in Assay Buffer.Step 4: Add equal volumes to Assay plate (total assay volume 10 uL).Step 5: Centrifuge plate, 1 min, 1000 rpm.Step 6: Detect fluorescence signal: ex: 320 nm; Em. 405 nm (EnVision), every 10 min. 60 min pre-incubation of enzyme with compound and 30 min reaction time after substrate addition.
Measurement: IC50 = 7.29 nM (pChEMBL 8.140000343322754)
Descriptors: MW 407.88, ALogP 2.52, HBA 5, HBD 2, PSA 87.74, QED 0.77
Compound (SMILES): COc1cc(OC(C)C)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: XIUDTKCWPZRTTG-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 > 1000 nM (pChEMBL 6)
Descriptors: MW 443.55, ALogP 5.37, HBA 7, HBD 0, PSA 65.3, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC[C@@H]2CO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MJBNLVZGJYYOOP-OAQYLSRUSA-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 = 2.754 nM (pChEMBL 8.5600004196167)
Descriptors: MW 488.59, ALogP 3.64, HBA 9, HBD 1, PSA 88.77, QED 0.38
Compound (SMILES): N#Cc1ccc2nnc(C(=O)N3CCC(c4cccc(F)c4C(F)(F)F)CC3)n2c1
InChIKey: TZIIUZZREBUIBM-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of recombinant human CYP2D6 expressed in insect cell microsomes in presence of NADPH-regenerating system after 15 to 45 mins by fluorescence probe substrate-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 417.37, ALogP 3.78, HBA 5, HBD 0, PSA 74.29, QED 0.6
Compound (SMILES): Cc1nc2c(N)cc(N3CCOCC3)nn2c1Nc1cccc(C(F)(F)F)c1CN1CC(O)C1
InChIKey: XHADQZSGBXAFFU-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 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 477.49, ALogP 2.4, HBA 9, HBD 3, PSA 104.18, QED 0.51
Compound (SMILES): Cc1ncc(F)cc1C1CCCN1c1ccn2ncc(C(=O)NC3CCC(O)CC3)c2n1
InChIKey: FDBFUEIJFKHRQU-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition Assay: Compounds of Formula I were screened for their ability to inhibit Tyk2 using the general enzyme inhibition assay method, in which the assay mixture contained 500 μM ATP, 8 μM Omnia Y12 peptide (Catalog # IVGN KPZ3121C; Invitrogen Corporation, Carlsbad, Calif.) and 1 nM Tyk2 in a total volume of 20 μL. Human Tyk2 kinase domain, comprising amino acids 886 to 1187 with 10 additional histidine residues (histidine tag) on the carboxy terminus, was expressed and purified from bacculovirus in-house at Array BioPharma Inc. (Boulder, Colo.). The histidine tag was cleaved after purification using standard conditions.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 438.51, ALogP 2.95, HBA 7, HBD 2, PSA 95.65, QED 0.65
Compound (SMILES): CCCCC[C@H](O)/C=C/[C@H]1CC(F)(F)C(=O)N1CCCCCCC(=O)O
InChIKey: PWZMQIUUWBQDQW-WFPWZJHXSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: SEAP Activity Assay: 1. Seed cells on an EP2 or EP4 STEP plate at a density of 40,000-80,000 cells/well in 200 ul of reduced serum medium containing 0.5% FBS. Place the plate in a 37° C. incubator with 5% CO2 and incubate overnight. 2. After 16-18 hours of incubation, aspirate the culture media from each well. 3. Add 200 ul of culture medium containing different concentration of test compounds to the assigned wells. For each test compound, at least 8 concentrations starting at highest 10 M and lowest 0.01 pM were tested. In addition each concentration had triplicates. A PGE2 curve (concentrations from lowest to highest, 0 pM, 0.384 pM, 1.92 pM, 9.6 pM, 48 pM, 240 pM, 1200 pM, and 6000 pM) was always run in parallel with test compounds. 4. After 6-8 hours of stimulation with test compounds and PGE2, 10 ul of culture media from each well was transferred to a corresponding well of a 96-well solid black plate. Cover the plate with the lid.
Measurement: EC50 = 0.059 nM (pChEMBL 10.229999542236328)
Descriptors: MW 375.46, ALogP 3.76, HBA 3, HBD 2, PSA 77.84, QED 0.38
Compound (SMILES): C[C@@H]1c2ncn(-c3ccccn3)c2CCN1C(=O)c1cccc(C(F)(F)F)c1Cl
InChIKey: OGZKVSNRBCPRRL-GFCCVEGCSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Radioligand Binding: uman or rat P2X7-1321N1 cells were collected and frozen @−80° C. On the day of the experiment, cell membrane preparations were made according to standard published methods. The total assay volume was 100 μl:10 μl compound (10x)+(b) 40 μl tracer (2.5×)+50 μl membrane (2x). The tracer used for the assay was tritiated A-804598. The compound can be prepared as described in the literature. (Donnelly-Roberts, D. Neuropharmacology 2008, 56 (1), 223-229.) Compounds, tracer and membranes were incubated for 1 hour @ 4° C. The assay was terminated by filtration (GF/B filters pre-soaked with 0.3% PEI) and washed with washing buffer (Tris-HCl 50 mM). The IC50 generated in the binding assay was corrected for tracer concentration and affinity of the tracer to derive at the affinity (Ki) of the test compounds. The data are presented in Tables 2 and 3 under the headings: P2X7 human Ki (μM) and P2X7 rat Ki (μM). Data are analyzed and graphed on Graphpad Prism 5. For analysis, each concentration point is averaged from triplicate values and the averaged values are plotted on Graphpad Prism.
Measurement: Ki = 39.8 nM (pChEMBL 7.400000095367432)
Descriptors: MW 420.82, ALogP 4.7, HBA 4, HBD 0, PSA 51.02, QED 0.6
Compound (SMILES): COc1ccc(-c2cc(C(N)=O)nc3cc(CCc4cnc(C)nc4)ccc23)c(F)c1
InChIKey: YFISEEHEDYLAHH-UHFFFAOYSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of Cav1.2 (unknown origin)
Measurement: IC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 416.46, ALogP 4.03, HBA 5, HBD 1, PSA 90.99, QED 0.51
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: FMWDLYTVSRVYQS-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 120.23 nM (pChEMBL 6.920000076293945)
Descriptors: MW 445.52, ALogP 4.05, HBA 8, HBD 1, PSA 85.53, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cccc(C#N)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WHVXBHTZGZQBQC-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 302 nM (pChEMBL 6.519999980926514)
Descriptors: MW 501.55, ALogP 4.5, HBA 9, HBD 0, PSA 101.98, QED 0.31
Compound (SMILES): CC(C)[C@H](Cc1ccc(C(F)(F)F)cc1)C(=O)NC[C@@]1(C2CC2)NC(=O)NC1=O
InChIKey: VXXYNKXMRXANKX-KXBFYZLASA-N
Target: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: In Vitro Fluorescence Assay: A continuous assay is used in which the substrate is a synthetic peptide containing a fluorescent group (7-methoxycoumarin, Mca), which is quenched by energy transfer to a 2,4-dinitrophenyl group. The substrate is the peptide Mca-PQGL-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-AR-OH. When the peptide is cleaved by MMP a large increase in fluorescence is observed. The source of the enzyme for this assay is full-length, recombinant, human pro-MMP-2 expressed in Chinese Hamster Ovary (CHO) cells that is subsequently activated by an organomercurial compound, 4-aminophenyl mercuric acetate (APMA). APMA is removed through a desalting column (MMP-2 Calbiochem catalog number PF023). The assay buffer consists of 100 mM Tris-HCl (pH 7.5), 100 mM NaCl, 10 mM CaCl2 and 10 uM human serum albumin Each well of the 96-well plates consists of a 100 uL reaction mixture consisting of assay buffer, MMP (final concentration of 0.2 nM, prepared by diluting in assay buffer).
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 411.42, ALogP 2.62, HBA 3, HBD 3, PSA 87.3, QED 0.6
Compound (SMILES): O=C(NCc1cccc(N2CCN(C(=O)Cc3n[nH]c(=O)[nH]3)CC2)c1)c1nc2ccccc2c(=O)[nH]1
InChIKey: FMEMUXYNXWETSE-UHFFFAOYSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Homo sapiens
UniProt: P78536
Assay: Inhibition of recombinant human TACE using Cy3-PLAQAV(Cy5Q-L-2,3-diaminopropionic acid)-RSSSR-NH2 as substrate measured after 40 mins by spectrofluorimetric method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 488.51, ALogP 0.16, HBA 7, HBD 4, PSA 159.94, QED 0.3
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC[C@@]3(C[C@H]3c3ccc(C(F)(F)F)cc3F)C2)n1C
InChIKey: ZIQDGXNDXRMRPM-HTAPYJJXSA-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 = 426.58 nM (pChEMBL 6.369999885559082)
Descriptors: MW 495.55, ALogP 5.3, HBA 7, HBD 0, PSA 59.98, QED 0.25
Compound (SMILES): CCOC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC(C4CC4)C4CC4)nc(Cl)nc31)[C@H](O)[C@@H]2O
InChIKey: IRHYVDDJDDMRKD-QNEDUEMWSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Inhibition of 5HT2C (unknown origin)
Measurement: Ki = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 447.92, ALogP 1.93, HBA 9, HBD 3, PSA 122.39, QED 0.43
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1.Cl
InChIKey: SUGJLIOPCUJKNU-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 25.7 nM (pChEMBL 7.590000152587891)
Descriptors: MW 502.62, ALogP 4.13, HBA 9, HBD 1, PSA 88.77, QED 0.33
Compound (SMILES): COc1cc(OC)cc(N(CCCC#N)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WAHZMINPROSVEH-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 36.31 nM (pChEMBL 7.440000057220459)
Descriptors: MW 428.5, ALogP 4.49, HBA 8, HBD 0, PSA 89.09, QED 0.38
Compound (SMILES): [2H]C([2H])([2H])Oc1cc(F)cc(N(CCN)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: AJGWZFROWJUKON-BMSJAHLVSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 117.49 nM (pChEMBL 6.929999828338623)
Descriptors: MW 392.44, ALogP 3.27, HBA 7, HBD 1, PSA 82.09, QED 0.54
Compound (SMILES): O=C(CN1CC(O)C(NC(=O)c2ccc(Cl)s2)C1)Nc1ccc(-n2ccccc2=O)cc1F
InChIKey: ARAVOODWJJJNBY-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Biochemical assay using fluorogenic peptide substrate.Step 1: Compound transfer to plate (50 nl).Step 2: Dilute FXa in Assay Buffer.Step 3: Dilute substrate in Assay Buffer.Step 4: Add equal volumes to Assay plate (total assay volume 10 uL).Step 5: Centrifuge plate, 1 min, 1000 rpm.Step 6: Detect fluorescence signal: ex: 320 nm; Em. 405 nm (EnVision), every 10 min. 60 min pre-incubation of enzyme with compound and 45 min reaction time after substrate addition.
Measurement: IC50 = 1.44 nM (pChEMBL 8.84000015258789)
Descriptors: MW 490.94, ALogP 2.11, HBA 7, HBD 3, PSA 103.67, QED 0.49
Compound (SMILES): COc1cc(OC)cc(N(C/C(C)=N/O)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RBVQYTAEUBJSEY-JFLMPSFJSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 138.04 nM (pChEMBL 6.860000133514404)
Descriptors: MW 432.48, ALogP 4.04, HBA 9, HBD 1, PSA 97.89, QED 0.27
Compound (SMILES): CCCCSc1nc2c(c(=O)n1-c1ccccc1)SCC2
InChIKey: RFJZKWIAOIBWJA-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: In Vitro Enzyme Assay: In vitro enzyme assays were conducted via the Ba(OH)2 precipitation method of Wang et al. (32) using recombinant human PDE11A4, PDE10A1, PDE5A1, PDE6C, PDE8A (BPS Bioscience Inc.), PDE7A (BIOMOL International), and PDE4A10 enzymes (gift from HengmingKe), in the presence of 100 nM cGMP, 30 nM cAMP, 500 nM cGMP, 1.7 μM cGMP, 10 nM cAMP, 15 nM cAMP, and 625 nM cAMP, respectively. Inhibitor concentrations that reduce enzyme activity by 50% (IC50) are presented. The values are means of at least three independent experiments.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 318.47, ALogP 3.77, HBA 5, HBD 0, PSA 34.89, QED 0.48
Compound (SMILES): COc1ccc(C#CCN(c2cc(OC)cc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)nc1
InChIKey: OXSXREVSJHOBMS-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 506.57, ALogP 4.64, HBA 9, HBD 0, PSA 87.42, QED 0.3
Compound (SMILES): COc1cc(OC)cc(N(CC2CCOCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: UZVFQJWFEJNXPR-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 147.91 nM (pChEMBL 6.829999923706055)
Descriptors: MW 459.55, ALogP 4.61, HBA 8, HBD 0, PSA 74.53, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCN)c4)nc3c2)c1
InChIKey: ZLIXAXDZDFQVBX-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 = 9.772 nM (pChEMBL 8.010000228881836)
Descriptors: MW 444.54, ALogP 4.02, HBA 8, HBD 1, PSA 91.32, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CCC(=O)N(C)OC)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YZFIDVOGSPMNRW-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 154.88 nM (pChEMBL 6.809999942779541)
Descriptors: MW 476.54, ALogP 3.6, HBA 9, HBD 0, PSA 94.84, QED 0.34
Compound (SMILES): COc1ccc(Cl)c(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: PNXHAMDNXPTINS-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 = 16.98 nM (pChEMBL 7.769999980926514)
Descriptors: MW 409.88, ALogP 3.82, HBA 7, HBD 1, PSA 76.3, QED 0.52
Compound (SMILES): COc1cc(OC)cc(N(CC2(CNC(C)C)COC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: FIOAXDHVMFVFQO-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 = 588.84 nM (pChEMBL 6.230000019073486)
Descriptors: MW 502.62, ALogP 4.2, HBA 9, HBD 1, PSA 86.56, QED 0.35
Compound (SMILES): O=C(CCNC(=O)c1ccc(Cl)s1)Nc1ccc(N2CCOCC2=O)cc1
InChIKey: ZAKACSMWGGBPNE-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Biochemical assay using fluorogenic peptide substrate.Step 1: Compound transfer to plate (50 nl).Step 2: Dilute FXa in Assay Buffer.Step 3: Dilute substrate in Assay Buffer.Step 4: Add equal volumes to Assay plate (total assay volume 10 uL).Step 5: Centrifuge plate, 1 min, 1000 rpm.Step 6: Detect fluorescence signal: ex: 320 nm; Em. 405 nm (EnVision), every 10 min. 60 min pre-incubation of enzyme with compound and 45 min reaction time after substrate addition.
Measurement: IC50 = 8.69 nM (pChEMBL 8.0600004196167)
Descriptors: MW 407.88, ALogP 2.52, HBA 5, HBD 2, PSA 87.74, QED 0.77
Compound (SMILES): COc1cc(OC(C)C)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: XIUDTKCWPZRTTG-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 443.55, ALogP 5.37, HBA 7, HBD 0, PSA 65.3, QED 0.36
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC[C@@H]2CO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MJBNLVZGJYYOOP-OAQYLSRUSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 2.818 nM (pChEMBL 8.550000190734863)
Descriptors: MW 488.59, ALogP 3.64, HBA 9, HBD 1, PSA 88.77, QED 0.38
Compound (SMILES): N#Cc1ccc2nnc(C(=O)N3CCC(c4cccc(F)c4C(F)(F)F)CC3)n2c1
InChIKey: TZIIUZZREBUIBM-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of recombinant human CYP3A4 expressed in insect cell microsomes in presence of NADPH-regenerating system after 15 to 45 mins by fluorescence probe substrate-based assay
Measurement: IC50 = 74000 nM (pChEMBL 4.130000114440918)
Descriptors: MW 417.37, ALogP 3.78, HBA 5, HBD 0, PSA 74.29, QED 0.6
Compound (SMILES): CCCCC[C@H](O)/C=C/[C@H]1CC(F)(F)C(=O)N1CCCCCCC(=O)O
InChIKey: PWZMQIUUWBQDQW-WFPWZJHXSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: SEAP Activity Assay: 1. Seed cells on an EP2 or EP4 STEP plate at a density of 40,000-80,000 cells/well in 200 ul of reduced serum medium containing 0.5% FBS. Place the plate in a 37° C. incubator with 5% CO2 and incubate overnight. 2. After 16-18 hours of incubation, aspirate the culture media from each well. 3. Add 200 ul of culture medium containing different concentration of test compounds to the assigned wells. For each test compound, at least 8 concentrations starting at highest 10 M and lowest 0.01 pM were tested. In addition each concentration had triplicates. A PGE2 curve (concentrations from lowest to highest, 0 pM, 0.384 pM, 1.92 pM, 9.6 pM, 48 pM, 240 pM, 1200 pM, and 6000 pM) was always run in parallel with test compounds. 4. After 6-8 hours of stimulation with test compounds and PGE2, 10 ul of culture media from each well was transferred to a corresponding well of a 96-well solid black plate. Cover the plate with the lid.
Measurement: EC50 = 205 nM (pChEMBL 6.690000057220459)
Descriptors: MW 375.46, ALogP 3.76, HBA 3, HBD 2, PSA 77.84, QED 0.38
Compound (SMILES): C[C@@H]1c2ncn(-c3ccccn3)c2CCN1C(=O)c1cccc(C(F)(F)F)c1Cl
InChIKey: OGZKVSNRBCPRRL-GFCCVEGCSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Ca2+ flux assay: 1321N1 cells expressing the recombinant human or rat P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 μl volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250× the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 μL of the compound into 300 μL of assay buffer. A further 3× dilution occurred when transferring 50 μL/well of the compound plate to 100 μL/well in the cell plate. Cells were incubated with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 μL/well of BzATP (final concentration is 250 μM BzATP (human and rat)). The fluorescence change was measured 180 seconds after adding the agonist. Peak fluorescence was plotted as a function of BzATP concentration using Origin 7 software.
Measurement: IC50 = 55.7 nM (pChEMBL 7.25)
Descriptors: MW 420.82, ALogP 4.7, HBA 4, HBD 0, PSA 51.02, QED 0.6
Compound (SMILES): COc1ccc(-c2cc(C(N)=O)nc3cc(CCc4cnc(C)nc4)ccc23)c(F)c1
InChIKey: YFISEEHEDYLAHH-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 416.46, ALogP 4.03, HBA 5, HBD 1, PSA 90.99, QED 0.51
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: FMWDLYTVSRVYQS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 758.58 nM (pChEMBL 6.119999885559082)
Descriptors: MW 445.52, ALogP 4.05, HBA 8, HBD 1, PSA 85.53, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cccc(C#N)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WHVXBHTZGZQBQC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 309.03 nM (pChEMBL 6.510000228881836)
Descriptors: MW 501.55, ALogP 4.5, HBA 9, HBD 0, PSA 101.98, QED 0.31
Compound (SMILES): CC(C)[C@H](Cc1ccc(C(F)(F)F)cc1)C(=O)NC[C@@]1(C2CC2)NC(=O)NC1=O
InChIKey: VXXYNKXMRXANKX-KXBFYZLASA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: In Vitro Fluorescence Assay: A continuous assay is used in which the substrate is a synthetic peptide containing a fluorescent group (7-methoxycoumarin, Mca), which is quenched by energy transfer to a 2,4-dinitrophenyl group. The substrate is the peptide Mca-PQGL-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionyl)-AR-OH. When the peptide is cleaved by MMP a large increase in fluorescence is observed. The source of the enzyme for this assay is full-length, recombinant, human pro-MMP-2 expressed in Chinese Hamster Ovary (CHO) cells that is subsequently activated by an organomercurial compound, 4-aminophenyl mercuric acetate (APMA). APMA is removed through a desalting column (MMP-2 Calbiochem catalog number PF023). The assay buffer consists of 100 mM Tris-HCl (pH 7.5), 100 mM NaCl, 10 mM CaCl2 and 10 uM human serum albumin Each well of the 96-well plates consists of a 100 uL reaction mixture consisting of assay buffer, MMP (final concentration of 0.2 nM, prepared by diluting in assay buffer).
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 411.42, ALogP 2.62, HBA 3, HBD 3, PSA 87.3, QED 0.6
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC[C@@]3(C[C@H]3c3ccc(C(F)(F)F)cc3F)C2)n1C
InChIKey: ZIQDGXNDXRMRPM-HTAPYJJXSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Functional Calcium Assay: CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were seeded into black walled clear-base 384-well plates at a density of 8,000 cells per well and grown overnight at 37° C. After washing with the assay buffer (20 mM HEPES, 145 mM NaCl, 5 mM KCl, 5.5 mM glucose, 1 mM MgCl2 and 2 mM CaCl2, pH 7.4) containing 2.5 mM Probenecid, cells were incubated with the cytoplasmic Ca2+ probe Fluo-4 AM at 1 μM (final concentration), 37° C. for 60 min. Plates were washed three times as above and placed into a Fluorometric Imaging Plate Reader (FLIPR Tetra, Molecular Devices) to monitor cell fluorescence (ex=470-495 nm, em=515-575 nm) before and after the addition of different concentrations of test compounds. Compounds of invention were dissolved in DMSO and 200-fold diluted with assay buffer plus 0.01% Pluronic F-127. Cells were exposed first to test compounds for 10 min, then to a submaximal concentration of the hD2 receptor agonist dopamine (EC80, 50-140 nM). The fluorescence before compound addition (baseline) and before and after addition of agonist challenge was monitored. The peak of Ca2+ stimulation (baseline subtracted) was plotted versus the concentration of test compound and the curve fitted using a four-parameter logistic equation (XLfit) to assess the agonist/antagonist potency and maximal response.
Measurement: Ki < 10000 nM (pChEMBL 5)
Descriptors: MW 495.55, ALogP 5.3, HBA 7, HBD 0, PSA 59.98, QED 0.25