lovingscience/chembl-v37-raw-activities huggingface dataset:
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 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 = 9.333 nM (pChEMBL 8.029999732971191)
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 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 = 54.95 nM (pChEMBL 7.260000228881836)
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: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal His6-tagged VEGFR2 (790 end residues) expressed in baculovirus infected insect Sf21 cells using Btn-Flt3 as substrate after 1 hr by time resolved fluorescence assay
Measurement: IC50 = 26.92 nM (pChEMBL 7.570000171661377)
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: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK3beta (unknown origin)
Measurement: IC50 = 6100 nM (pChEMBL 5.210000038146973)
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 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 = 134.9 nM (pChEMBL 6.869999885559082)
Descriptors: MW 432.53, ALogP 4.17, HBA 7, HBD 2, PSA 88.19, QED 0.41
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 BAP-tagged AMPK alpha1/beta1/gamma1 assessed as protection from Thr172 residue dephosphorylation preincubated for 15 mins followed by addition of PP2a for 60 mins and using okadaic acid by DELFIA protection assay
Measurement: EC50 = 28.2 nM (pChEMBL 7.550000190734863)
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: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 430.45, ALogP 4.15, HBA 5, HBD 2, PSA 76.66, QED 0.66
Compound (SMILES): CC(C)(C)c1ccc(N2C(=O)CC[C@@H]2COCc2ccc(C(=O)O)o2)cc1
InChIKey: BADIOVUTPYVHGM-MRXNPFEDSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Agonist activity at human recombinant EP2 receptor expressed in HEK-EBNA cells incubated for 30 mins by cAMP accumulation assay
Measurement: EC50 = 28 nM (pChEMBL 7.550000190734863)
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 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
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 < 1000 nM (pChEMBL 6)
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 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 = 4.571 nM (pChEMBL 8.34000015258789)
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 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 = 4.365 nM (pChEMBL 8.359999656677246)
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 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 using Btn-Flt3 as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 6.607 nM (pChEMBL 8.180000305175781)
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 = 6.6 nM (pChEMBL 8.180000305175781)
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 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 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 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
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: 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 = 489.78 nM (pChEMBL 6.309999942779541)
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 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 = 14.13 nM (pChEMBL 7.849999904632568)
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 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 = 3.548 nM (pChEMBL 8.449999809265137)
Descriptors: MW 514.51, ALogP 4.25, HBA 8, HBD 1, PSA 94.4, QED 0.33
Compound (SMILES): Cc1ccc(CNC[C@H]2CC[C@H](c3nnn4cnc5[nH]ccc5c34)CC2)s1
InChIKey: UXEHANJJLFQUIY-SHTZXODSSA-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.
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
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 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 = 4.074 nM (pChEMBL 8.390000343322754)
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: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of TRKB (unknown origin) in presence of [gamma33P]ATP by radiometric HotSpot assay
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
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 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 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: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal His6-tagged VEGFR2 (790 end residues) expressed in baculovirus infected insect Sf21 cells using Btn-Flt3 as substrate after 1 hr by time resolved fluorescence assay
Measurement: IC50 = 489.78 nM (pChEMBL 6.309999942779541)
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-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Cell Adhesion Assay : A panel of cell lines and integrin ligands were developed to allow rapid examination of potency and specificity of inhibitors against all 8 integrins that recognize RGD sequences in ligands. A subset of these was used to generate the very encouraging data about 8 shown above. These cell lines were used to calculate IC50 concentrations for each inhibitor synthesized to rapidly generate structure activity information to drive subsequent modification and synthesis. Inhibitors were evaluated for showing better potency/selectivity in CCl4-induced liver fibrosis.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 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 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14831
Assay: Antagonist activity at mGluR7 (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 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 = 3.162 nM (pChEMBL 8.5)
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: 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 = 990 nM (pChEMBL 6)
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 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 = 5.754 nM (pChEMBL 8.239999771118164)
Descriptors: MW 543.59, ALogP 4.54, HBA 9, HBD 2, PSA 103.35, QED 0.24
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 EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: FLIPR Assay: Calciium Signal Studies of the Flipr. Cells were seeded at a density of 5×104 cells per well in Biocoati® Poly-D-lysine-coated black-wall, clear-bottom 96-well plates (Becton-Dickinson) and allowed to attach overnight in an incubator at 37° C. Cells were then washed two times with HBSS-HEPES buffer (Hanks Balanced Salt Solution without bicarbonate and phenol red, 20 mM HEPES, pH 7.4) using a Denley Cellwash plate washer (Labsystems). After 45 minutes of dye-loading in the dark, using the calcium-sensitive dye Fluo-4 AM at a final concentration of 2 μM, plates were washed four times with HBSS-HEPES buffer to remove excess dye leaving 100 μl in each well. Plates were re-equilibrated to 37° C. for a few minutes. Cells were excited with an Argon laser at 488 nm, and emission was measured through a 510-570 nm bandwidth emission filter (FLIPR, Molecular Devices, Sunnyvale, Calif.). Drug solution was added in a 50 μl volume to each well to give the desired final concentration.
Measurement: EC50 = 952 nM (pChEMBL 6.019999980926514)
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: 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 = 79.43 nM (pChEMBL 7.099999904632568)
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 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 = 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 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 = 60.26 nM (pChEMBL 7.21999979019165)
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 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 = 1.66 nM (pChEMBL 8.779999732971191)
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 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC as substrate after 30 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 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 = 4.677 nM (pChEMBL 8.329999923706055)
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: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Cell Based Assay: ATR (Ataxia Telangiectasia+Rad3-related kinase) is a PI3-kinase-related kinase which phosphorylates multiple substrates on serine or threonine residues in response to DNA damage or replication blocks. Chk1, a downstream protein kinase of ATR, plays a key role in DNA damage checkpoint control. Activation of Chk1 involves phosphorylation of Ser317 and Ser345 (the latter regarded as the preferential target for phosphorylation/activation by ATR).This was a cell based assay to measure inhibition of ATR kinase, by measuring a decrease in phosphorylation of Chk1 (Ser 345) in HT29 cells, following treatment with compound and the UV mimetic 4NQO (Sigma #N8141). HT29 cells (ECACC #85061109) were seeded into 384 well assay plates (Costar #3712) at a density of 6000 cells/well in 40 ul EMEM medium containing 1% L glutamine and 10% FBS and allowed to adhere overnight. The following morning compounds in 100% DMSO were added to assay plates by acoustic dispensing.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
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 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BFC 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: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5-HT1A receptor by liquid scintillation counting method
Measurement: Ki = 1096.48 nM (pChEMBL 5.960000038146973)
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 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 = 2.455 nM (pChEMBL 8.609999656677246)
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 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 = 25.7 nM (pChEMBL 7.590000152587891)
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 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 = 2.692 nM (pChEMBL 8.569999694824219)
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: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at 5HT2B (unknown origin)
Measurement: EC50 = 160 nM (pChEMBL 6.800000190734863)
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 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 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 432.53, ALogP 4.17, HBA 7, HBD 2, PSA 88.19, QED 0.41
Compound (SMILES): O=C(O)c1c[nH]c2cc(Cl)c(-c3ccc(C4(O)CCC4)cc3)cc12
InChIKey: FHQXLWCFSUSXBF-UHFFFAOYSA-N
Target: AMPK alpha2/beta1/gamma1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P54619
Assay: Activation of recombinant human AMPK alpha2/beta1/gamma1 using Cy5-labelled SAMS as substrate assessed as protection from Thr172 residue dephosphorylation preincubated for 15 mins followed by incubation with PP2a for 60 mins measured 60 mins post okadaic acid/Cy5-labelled SAMS and ATP addition by TR-FRET assay
Measurement: EC50 = 6.8 nM (pChEMBL 8.170000076293945)
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 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
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 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 430.45, ALogP 4.15, HBA 5, HBD 2, PSA 76.66, QED 0.66
Compound (SMILES): CC(C)(C)c1ccc(N2C(=O)CC[C@@H]2COCc2ccc(C(=O)O)o2)cc1
InChIKey: BADIOVUTPYVHGM-MRXNPFEDSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Displacement of [3H]PGE2 from from human EP2 receptor expressed in HEK293 cells at pH 6.0 membranes incubated for 60 mins
Measurement: EC50 = 189 nM (pChEMBL 6.71999979019165)
Descriptors: MW 371.43, ALogP 3.99, HBA 4, HBD 1, PSA 79.98, QED 0.83
Compound (SMILES): CNCCN(c1cc(F)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: OJURKTZIXKTKOA-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 = 7.943 nM (pChEMBL 8.100000381469727)
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 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 = 7.943 nM (pChEMBL 8.100000381469727)
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 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 = 1.202 nM (pChEMBL 8.920000076293945)
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 = 170 nM (pChEMBL 6.769999980926514)
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 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 = 3.388 nM (pChEMBL 8.470000267028809)
Descriptors: MW 475.55, ALogP 3.41, HBA 9, HBD 2, PSA 105.76, QED 0.34
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 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 = 2511.89 nM (pChEMBL 5.599999904632568)
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 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 = 33.11 nM (pChEMBL 7.480000019073486)
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 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 = 1.072 nM (pChEMBL 8.970000267028809)
Descriptors: MW 514.51, ALogP 4.25, HBA 8, HBD 1, PSA 94.4, QED 0.33
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 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 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: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of TRKC (unknown origin) in presence of [gamma33P]ATP by radiometric HotSpot assay
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
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 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 = 3.236 nM (pChEMBL 8.489999771118164)
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 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 = 158.49 nM (pChEMBL 6.800000190734863)
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-4/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Binding affinity to human integrin alpha4beta1 incubated for 6 hrs by radioligand binding assay
Measurement: Kd = 0.7943 nM (pChEMBL 9.100000381469727)
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 8 (SINGLE PROTEIN), Homo sapiens
UniProt: O00222
Assay: Antagonist activity at mGluR8 (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 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 = 4.266 nM (pChEMBL 8.369999885559082)
Descriptors: MW 507.04, ALogP 5.32, HBA 8, HBD 0, PSA 68.54, QED 0.3
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 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 = 3.802 nM (pChEMBL 8.420000076293945)
Descriptors: MW 543.59, ALogP 4.54, HBA 9, HBD 2, PSA 103.35, QED 0.24
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: Thromboxane A2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21731
Assay: FLIPR Assay: Calciium Signal Studies of the Flipr. Cells were seeded at a density of 5×104 cells per well in Biocoati® Poly-D-lysine-coated black-wall, clear-bottom 96-well plates (Becton-Dickinson) and allowed to attach overnight in an incubator at 37° C. Cells were then washed two times with HBSS-HEPES buffer (Hanks Balanced Salt Solution without bicarbonate and phenol red, 20 mM HEPES, pH 7.4) using a Denley Cellwash plate washer (Labsystems). After 45 minutes of dye-loading in the dark, using the calcium-sensitive dye Fluo-4 AM at a final concentration of 2 μM, plates were washed four times with HBSS-HEPES buffer to remove excess dye leaving 100 μl in each well. Plates were re-equilibrated to 37° C. for a few minutes. Cells were excited with an Argon laser at 488 nm, and emission was measured through a 510-570 nm bandwidth emission filter (FLIPR, Molecular Devices, Sunnyvale, Calif.). Drug solution was added in a 50 μl volume to each well to give the desired final concentration.
Measurement: EC50 = 5598 nM (pChEMBL 5.25)
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: 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 = 40.74 nM (pChEMBL 7.389999866485596)
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 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 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 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 = 338.84 nM (pChEMBL 6.46999979019165)
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 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 = 16.22 nM (pChEMBL 7.789999961853027)
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 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 5.300000190734863)
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 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 = 21.88 nM (pChEMBL 7.659999847412109)
Descriptors: MW 473.58, ALogP 3.09, HBA 9, HBD 1, PSA 80.57, QED 0.42
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 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) using BQ 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: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5-HT2A receptor by liquid scintillation counting method
Measurement: Ki = 1862.09 nM (pChEMBL 5.730000019073486)
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 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 = 5.623 nM (pChEMBL 8.25)
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 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 = 128.82 nM (pChEMBL 6.889999866485596)
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 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 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 434.5, ALogP 2.6, HBA 9, HBD 2, PSA 111.55, QED 0.41
Compound (SMILES): COc1ccc(OC)c(N(CCNC(C)C)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: FXBPODZDHNYGBT-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 432.53, ALogP 4.17, HBA 7, HBD 2, PSA 88.19, QED 0.41
Compound (SMILES): O=C(O)c1c[nH]c2cc(Cl)c(-c3ccc(C4(O)CCC4)cc3)cc12
InChIKey: FHQXLWCFSUSXBF-UHFFFAOYSA-N
Target: 5'-AMP-activated protein kinase catalytic subunit alpha-1/beta-1/gamma-1 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P80385
Assay: Activation of recombinant rat AMPK alpha1/beta1/gamma1 using Cy5-labelled SAMS as substrate assessed as protection from Thr172 residue dephosphorylation preincubated for 15 mins followed by incubation with PP2a for 60 mins measured 60 mins post okadaic acid/Cy5-labelled SAMS and ATP addition by TR-FRET assay
Measurement: EC50 = 7 nM (pChEMBL 8.149999618530273)
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 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
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: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 430.45, ALogP 4.15, HBA 5, HBD 2, PSA 76.66, QED 0.66
Compound (SMILES): CNCCN(c1cc(F)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: OJURKTZIXKTKOA-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 = 45.71 nM (pChEMBL 7.340000152587891)
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 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 = 38.02 nM (pChEMBL 7.420000076293945)
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 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 = 16.98 nM (pChEMBL 7.769999980926514)
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 = 7.6 nM (pChEMBL 8.119999885559082)
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 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 = 44.67 nM (pChEMBL 7.349999904632568)
Descriptors: MW 475.55, ALogP 3.41, HBA 9, HBD 2, PSA 105.76, QED 0.34
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 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 presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
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 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 = 144.54 nM (pChEMBL 6.840000152587891)
Descriptors: MW 499.57, ALogP 3.73, HBA 9, HBD 1, PSA 94.76, QED 0.4