lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#Cc1ccc(F)cn1)c1nc2cccc(Cl)c2c(=O)n1-c1cccc(-c2ccccc2)c1
InChIKey: WFVHTFYAMBXFNL-FQEVSTJZSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: PI3K isoforms were assayed under initial rate conditions in the presence of 25 mM Hepes (pH 7.4), and 2xKm ATP (100-300 uM), 10 uM PIP2, 5% glycerol, 5 mM MgCl2, 50 mM NaCl, 0.05% (v/v) Chaps, 1 mM dithiothreitol, 1% (v/v) DMSO at the following concentrations for each isoform: PI3K alpha, beta, delta, and gamma at 50 picomolar (pM) and PI3Kgamma at 2 nanomolar (nM). After an assay reaction time of 30 minutes at 25° C., reactions were terminated with a final concentration of 10 mM EDTA, 10 nM labeled-PIP3, and 35 nM Europium labeled GRP-1 detector protein before reading TR-FRET on an Envision plate reader (Ex: 340 nm; Em: 615/665 nm; 100 us delay and 500 us read window).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 588.05, ALogP 6.19, HBA 8, HBD 2, PSA 111.61, QED 0.23
Compound (SMILES): CC(=O)N1CCC(C(=O)N2CC[C@](c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3)(S(=O)(=O)c3ccc(F)cc3)C2)CC1
InChIKey: ZCVYLZVBYDUMQY-DEOSSOPVSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Agonist activity at LXRalpha (unknown origin) expressed in African green monkey CV1 cells
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 626.57, ALogP 5.28, HBA 4, HBD 0, PSA 74.76, QED 0.33
Compound (SMILES): COc1cc(-c2ccc(Cl)c(C)c2)ccc1-n1c(=O)ccc2cc(S(=O)(=O)Nc3ccon3)ccc21
InChIKey: IPKXOBOEJFTCKO-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using diclofenac as substrate
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 521.98, ALogP 5.42, HBA 7, HBD 1, PSA 103.43, QED 0.32
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(C#CCO)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: DIZNSMNZOQAXRV-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 450.5, ALogP 2.72, HBA 8, HBD 2, PSA 111.85, QED 0.41
Compound (SMILES): CCCCCC(=O)c1ccc(N2C(=O)CC[C@@H]2CCCc2ccc(C(=O)O)s2)cc1
InChIKey: IIIMTHLYWCQJTA-SFHVURJKSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Agonist activity at human recombinant EP3A receptor expressed in HEK293 cells assessed as effect on calcium accumulation by Fluo-4 AM dye based FLIPR assay
Measurement: EC50 = 2345 nM (pChEMBL 5.630000114440918)
Descriptors: MW 427.57, ALogP 5.73, HBA 4, HBD 1, PSA 74.68, QED 0.37
Compound (SMILES): COc1cc(OC)cc(N(CC(NC(C)C)C(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: NFVFGSNTTFYGGF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (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 488.64, ALogP 5.21, HBA 8, HBD 1, PSA 77.33, QED 0.33
Compound (SMILES): CCCCCC(O)c1ccc([C@H]2CCC(=O)[C@@H]2C/C=C\CCCC(=O)O)cc1
InChIKey: BCHXZTZHDBHTJJ-ITDWLTTLSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Agonist activity at human recombinant EP2 receptor expressed in HEK293 cells assessed as effect on calcium accumulation by Fluo-4 AM dye based FLIPR assay
Measurement: EC50 = 1011 nM (pChEMBL 6)
Descriptors: MW 386.53, ALogP 5.56, HBA 3, HBD 2, PSA 74.6, QED 0.36
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3c(Cl)cccc3Cl)CC2)C1
InChIKey: OCGBOKGBZRYUTL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.).
Measurement: IC50 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 550.45, ALogP 4.75, HBA 7, HBD 2, PSA 118.76, QED 0.37
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccnc(F)c4)cc23)c1F
InChIKey: VXWGODJACAPXND-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using CEC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 474.46, ALogP 4.42, HBA 5, HBD 2, PSA 104.81, QED 0.3
Compound (SMILES): CC1(C)[C@H]2CC[C@@H](CCN3[C@@H]4CCC[C@H]3C[C@@H](n3c(=O)c(N5CC[C@@H]5C(=O)O)nc5ccccc53)C4)[C@@H]1C2
InChIKey: OPNHKXQPNQNQOK-DUWFNVGLSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: In Vitro Delta-Opioid Receptor Binding Assay: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressed in CHO-K1 cells; Perkin Elmer) in a final volume of 500 μL binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25 μM unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25 °C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma-Aldrich). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 500 μL ice-cold binding buffer. Filter plates were subsequently dried at 50 °C. for 1-2 hours. Fifty μL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 1770 nM (pChEMBL 5.75)
Descriptors: MW 518.7, ALogP 5.08, HBA 6, HBD 1, PSA 78.67, QED 0.57
Compound (SMILES): O=C(OC(C(F)(F)F)C(F)(F)F)N1CCN(Cc2ccc(Cl)cc2N2CCOCC2)CC1
InChIKey: BICIAYLKEQATFV-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of MGLL derived from human PC3 cell lysates preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 489.84, ALogP 3.92, HBA 5, HBD 0, PSA 45.25, QED 0.6
Compound (SMILES): C[C@H](Nc1cc(C(N)=O)nc(-c2ccc(Oc3ccc(Cl)cn3)cc2)n1)C(N)=O
InChIKey: MZOPJCMGXOIERS-JTQLQIEISA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Electrophysiology Assay: Cells: The hNav1.7 expressing HEK-293 cells were plated on 35 mm culture dishes pre-coated with poly-D-lysine in standard DMEM culture media (Mediatech, Inc., Herndon, Va.) and incubated in a 5% CO2 incubator at 37° C. CuItured cells were used approximately 12-48 h after plating.Electrophysiology: On the day of experimentation, the 35 mm dish was placed on the stage of an inverted microscope equipped with a perfusion system that continuously perfuses the culture dish with fresh recording media. A gravity driven superfusion system was used to apply test solutions directly to the cell under evaluation. This system consists of an array of glass pipette glass connected to a motorized horizontal translator. The outlet of the shooter was positioned approximately 100 μm from the cell of interest.Whole cell currents were recorded using the whole-cell patch clamp configuration using an Axopatch 200B amplifier (Axon Instruments, Foster City Calif.), 1322A A/D converter (Axon Instruments) and pClamp software (v. 8; Axon Instruments) and stored on a personal computer. Gigaseals were formed and the whole-cell configuration was established in voltage clamp mode, and membrane currents generated by hNav1.7 were recorded in gap-free mode. Borosilicate glass pipettes have resistance values between 1.5 and 2.0 MΩ when filled with pipette solution and series resistance (<5 MΩ) was compensated 75-80%. Signals were sampled at 50 kHz and low pass filtered at 3 kHz.Voltage Protocols: After establishing the whole-cell configuration in voltage clamp mode, two voltage protocols were run to establish: 1) the holding potential; and 2) the test potential for each cell.
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 412.84, ALogP 2.37, HBA 7, HBD 3, PSA 146.11, QED 0.54
Compound (SMILES): COC(=O)CCCCS(C)(=O)=NC(=O)c1cnc(N)c(C#Cc2cccc(NC(=O)c3cccc(C(F)(F)F)c3)c2)c1
InChIKey: DLUVOPPDOKCLLX-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: PDGFRbeta : Automated FLIPR (Fluorometric Imaging Plate Reader) technology was used to screen for inhibitors of PDGF-induced increases in intracellular calcium levels in fluorescent dye loaded endothelial cells. NHDF-Ad (Normal Human Dermal Fibroblasts, Adult; Lonza) were seeded in 384-well fibronectin coated black-walled plates overnight @ 37° C./5% CO2. Cells were loaded with calcium indicator Fluo-4 for 45 minutes at 37° C. Cells were washed 2 times (Elx405, Biotek Instruments) to remove extracellular dye. For screening, cells were pre-incubated with test agents for 30 minutes, at a single concentration (10 uM) or at concentrations ranging from 0.0001 to 10.0 uM followed by PDGF-BB stimulation (30 ng/mL). Changes in fluorescence at 516 nm were measured simultaneously in all 384 wells using a cooled CCD camera. Data were generated by determining max-min fluorescence levels for unstimulated, stimulated, and drug treated samples.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 600.62, ALogP 4.92, HBA 7, HBD 2, PSA 140.81, QED 0.21
Compound (SMILES): CNC(C)(C)CCS(=O)(=O)CC[C@@H]1OCC[C@@]2(S(=O)(=O)c3ccc(Cl)cc3)c3c(F)ccc(F)c3OC[C@@H]12
InChIKey: GMFRTIZFLPGMOQ-NHZRIVAWSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes preincubated for 30 mins after 30 secs by LC/MS/MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 592.13, ALogP 4.28, HBA 7, HBD 1, PSA 98.77, QED 0.46
Compound (SMILES): Cn1c(=O)c2c(CC(=O)Nc3nc(-c4ccc(C(F)(F)F)c(F)c4)cs3)coc2n(C)c1=O
InChIKey: GUXDRJQXNCINLK-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 482.42, ALogP 3.29, HBA 8, HBD 1, PSA 99.13, QED 0.45
Compound (SMILES): N[C@H](C(=O)O)C(NS(=O)(=O)c1cc(F)c(F)cc1F)C(=O)O
InChIKey: BSABROAMVRXYPC-JAMMHHFISA-N
Target: Excitatory amino acid transporter 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P43004
Assay: Inhibition of [3H]-D-Asp uptake at human EAAT2 expressed in HEK293 cells measured after 3 mins by TopCount method
Measurement: IC50 = 22387.21 nM (pChEMBL 4.650000095367432)
Descriptors: MW 342.25, ALogP -0.75, HBA 5, HBD 4, PSA 146.79, QED 0.5
Compound (SMILES): O=C(O)CC1CCC2(CC1)CCN(c1ccccc1Cl)CC2
InChIKey: SDSAFMLNHFPXQO-UHFFFAOYSA-N
Target: Free fatty acid receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: Q7TMA4
Assay: Agonist activity at mouse GPR120 expressed in CHOK1 cells assessed as induction of IP1 accumulation after 60 mins by HTRF assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 321.85, ALogP 4.59, HBA 2, HBD 1, PSA 40.54, QED 0.88
Compound (SMILES): CC(C)(C)C[C@@H]1N[C@@H](C(=O)NC2CCC(O)CC2)[C@H](c2cccc(Cl)c2F)[C@]12C(=O)Nc1cc(F)c(F)cc12
InChIKey: CPVLFAPAIXRGNV-DJJHDAFRSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Fluorescence-Polarization Binding Assay: The binding affinity of the MDM2 inhibitors was determined using an optimized, sensitive and quantitative fluorescence polarization-based (FP-based) binding assay using a recombinant human His-tagged MDM2 protein (residues 1-118) and a fluorescently tagged p53-based peptide.The design of the fluorescence probe was based upon a previously reported high-affinity p53-based peptidomimetic compound (5-FAM-beta Ala-beta Ala-Phe-Met-Aib-pTyr-(6-Cl-LTrp)-Glu-Ac3c-Leu-Asn-NH2 (SEQ ID NO: 1)) Garcia-Echeverria et al., J. Med. Chem. 43: 3205-3208 (2000)). This tagged peptide is called PMDM6-F. The Kd value of PMDM6-F with the recombinant MDM2 protein was determined from the saturation curve. MDM2 protein was serially double diluted in a Dynex 96-well, black, round-bottom plate, and the PMDM6-F peptide was added at 1 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 ug/mL bovine gamma globulin; 0.02% sodium azide, 0.01% Triton X-100).
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 564.05, ALogP 4.93, HBA 4, HBD 4, PSA 90.46, QED 0.42
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1CCc2c(nnn2-c2ccccn2)C1
InChIKey: LYZPFJOSYJKSFW-UHFFFAOYSA-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 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 407.78, ALogP 3.53, HBA 5, HBD 0, PSA 63.91, QED 0.65
Compound (SMILES): CNCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cn[nH]c3)nc2c1
InChIKey: QIEVSBKOXPAREF-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (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 404.47, ALogP 3.39, HBA 7, HBD 2, PSA 88.19, QED 0.47
Compound (SMILES): COc1cc(N2CCC(N3CCN(S(C)(=O)=O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: HJVBXNCPDWDXAB-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human full length ErbB2 expressed in baculovirus expression system assessed as decrease in transfer of gamma-phosphate from ATP onto tyrosine residue of biotinylated peptide substrate preincubated for 1 hr followed by substrate addition measured after 90 mins by HTRF method
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 823.93, ALogP 6.3, HBA 12, HBD 2, PSA 146.53, QED 0.15
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2ccc(Oc3ccnc(Nc4ccc5[nH]ncc5c4)n3)c3ccccc23)n(-c2cccc(OCCN3CCOCC3)c2)n1
InChIKey: MMEJLCRBNBQORJ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P49840
Assay: GSK 3α Enzyme Inhibition Assay: The inhibitory activities of compounds of the invention against the GSK 3α enzyme isoform (Invitrogen), are evaluated by determining the level of activation/phosphorylation of the target peptide. The GSK3-α protein (500 ng/mL, 2.5 uL) is mixed with the test compound (2.5 uL at either 4 ug/mL, 0.4 ug/mL, 0.04 ug/mL, or 0.004 ug/mL) for 2 hr at RT. The FRET peptide (8 uM, 2.5 uL), which is a phosphorylation target for GSK3α, and ATP (40 uM, 2.5 uL) are then added to the enzyme/compound mixture and the resulting mixture incubated for 1 hr. Development reagent (protease, 5 uL) is added for 1 hr prior to detection in a fluorescence microplate reader (Varioskan Flash, ThermoFisher Scientific).
Measurement: IC50 = 1980 nM (pChEMBL 5.699999809265137)
Descriptors: MW 738.85, ALogP 7.88, HBA 11, HBD 4, PSA 156.37, QED 0.1
Compound (SMILES): O[C@H]1[C@@H](O)C[C@@]2(n3cnc4c(NC5CC6CCC5C6)nc(Cl)nc43)C[C@@H]12
InChIKey: CXBQRTGJJCJHGX-DOROLRBCSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Radioligand Binding Assay: Radioligand binding assays at A1, A2A, and A3ARs were performed according to the procedures described previously. Each tube in the binding assay contained 100 uL of membrane suspension (20 ug of protein), 50 pt of a stock solution of agonist radioligand, and 50 uL of increasing concentrations of the test ligands in Tris-HCl buffer (50 mM, pH 7.5) containing 10 mM MgCl2. Nonspecific binding was determined using a final concentration of 10 uM NECA, a non-specific agonist, diluted with the buffer.The mixtures were incubated at 25° C. for 60 min. Binding reactions were terminated by filtration through Whatman GF/B filters under a reduced pressure using a MT-24 cell harvester (Brandell, Gaithersburg, Md.). Filters were washed three times with 5 ml of 50 mM ice-cold Tris-HCl buffer (pH 7.5). The radioactive agonists [3H]R-PIA and [3H]CGS21680 were used for the A1 and A2AAR assays, respectively, while [125I]AB-MECA was used for the A3AR assay.
Measurement: Ki = 4080 nM (pChEMBL 5.389999866485596)
Descriptors: MW 375.86, ALogP 1.92, HBA 7, HBD 3, PSA 96.09, QED 0.71
Compound (SMILES): O=C(COc1ccc2cc(C(O)(C(F)(F)F)C(F)(F)F)c(O)cc2c1)NCc1ccccc1
InChIKey: WZHNGXGUEZJUEM-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 22 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2R2
Assay: Inhibition of recombinant LYP (unknown origin) using pNPP as substrate by spectrophotometric method
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 473.37, ALogP 4.55, HBA 4, HBD 3, PSA 78.79, QED 0.46
Compound (SMILES): COc1cc(N2CCC(N3CCN(S(C)(=O)=O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3cc(F)ccn23)n1
InChIKey: WEJYDRZQJWJEGQ-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of recombinant human full length ErbB2 expressed in baculovirus expression system assessed as decrease in transfer of gamma-phosphate from ATP onto tyrosine residue of biotinylated peptide substrate preincubated for 1 hr followed by substrate addition measured after 90 mins by HTRF method
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 811.89, ALogP 6.43, HBA 11, HBD 2, PSA 137.3, QED 0.16
Compound (SMILES): CC(C)C(=O)N1CC[C@](C)(N2CCc3c(-c4cnc(N)nc4)nc(N4CCOCC4)nc32)C1
InChIKey: KFSXZQWLLQTWSR-QHCPKHFHSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human PI3K p110beta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 452.56, ALogP 1.36, HBA 9, HBD 1, PSA 113.6, QED 0.73
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(-c3ccc4nc(N)sc4c3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: FHXVEMGLXJPKKI-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 544.64, ALogP 5.24, HBA 10, HBD 2, PSA 130.53, QED 0.31
Compound (SMILES): N#CC1CCCN1C(=O)CNC(=O)c1ccnc2ccccc12
InChIKey: MTHMMXFBHKGAAI-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHL4
Assay: Enzymatic Assay: Enzyme activities were determined kinetically in a final volume of 200 μl for 10 minutes at 37° C. by measuring the initial velocities of pNA release (405 nm) from the substrate using a Spectramax plus microtiterplate reader (Molecular devices). One unit of enzyme activity was defined as the amount of enzyme that catalyzes the release of 1 μmol pNA from the substrate per minute under assay conditions. The chromogenic substrate Gly-Pro-p-nitroanilide (100 μmol/l) was used at pH 8.3 for DPP IV, Lys-Ala-p-nitroanilide (1 mmol/l) at pH 5.5 for DPP II, Ala-Pro-p-nitroanilide (300 μmol/l) at pH 7.4 for DPP9 and Ala-Pro-p-nitroanilide (2 mmol/l) at pH 7.4 for FAP activity measurement. To evaluate the endopeptidase activity of FAP and the influence of inhibitors thereon, Z-Gly-Pro-AMC and Z-Gly-Pro-p-nitroanilide were used at a final concentration of 300 and 100 μmol/l, respectively. The substrate concentrations were chosen around the Km value obtained under the assay conditions used. Buffer compositions for the DPP assays were reported before in the purification articles−vide supra. The FAP assay buffer consisted of 50 mM Tris pH7.4 containing 100 mmol/l NaCl and 0.1 mg/ml bovine serum albumin. The PREP activity was measured as described by Brandt et al. using the chromogenic substrate Z-Gly-Pro-p-nitroanilide (0.25 mmol/l) at pH 7.5 in the presence of 10 mmol/l DTT. Test compounds were dissolved and diluted in DMSO (final concentration DMSO during assay 5% v/v) except for FAP where dilution of the inhibitor was done in water. Inhibitors are pre-incubated with the enzyme for 15 min at 37° C. before starting the assay by the addition of substrate. The concentration of enzyme and of inhibitor during the preincubation is double of the final concentration during activity measurement.
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 308.34, ALogP 1.48, HBA 4, HBD 1, PSA 86.09, QED 0.93
Compound (SMILES): N#CCC1(n2cc(-c3c(C#N)cnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccc(C#N)c(F)c3)CC2)C1
InChIKey: KEFGHDLGYTZSEG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.).
Measurement: IC50 > 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 533.57, ALogP 3.54, HBA 8, HBD 1, PSA 141.42, QED 0.41
Compound (SMILES): C=CC(=O)N(C)CCn1nc(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc21
InChIKey: ZFHREWWRBHSDLZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 = 6.62 nM (pChEMBL 8.180000305175781)
Descriptors: MW 414.47, ALogP 3.51, HBA 7, HBD 1, PSA 99.16, QED 0.46
Compound (SMILES): CN(C)C(=O)Oc1cccc(C(=O)/C=C/c2ccc(O)cc2)c1
InChIKey: DQPVCSPAVCOSNM-DHZHZOJOSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Non-competitive inhibition of human serum BChE using S-Butyrylthiocholine iodide as substrate preincubated for 15 mins followed by substrate addition by Lineweaver-Burk plot analysis
Measurement: Ki = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 311.34, ALogP 3.35, HBA 4, HBD 1, PSA 66.84, QED 0.69
Compound (SMILES): N#CCC1(n2cc(-c3ccnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(C(F)(F)F)ncc3Cl)CC2)C1
InChIKey: GCOHIGJKONXAEP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro JAK Kinase Assay: Compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.).
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 568.99, ALogP 4.72, HBA 7, HBD 1, PSA 106.73, QED 0.37
Compound (SMILES): COc1ccc(-c2ccc3ncnc(O[C@H]4CCN(C)C4)c3c2)cc1OC
InChIKey: JBCVLFFNJOTCGR-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3K-beta (unknown origin) by KinaseGlo assay
Measurement: IC50 = 1480 nM (pChEMBL 5.829999923706055)
Descriptors: MW 365.43, ALogP 3.4, HBA 6, HBD 0, PSA 56.71, QED 0.69
Compound (SMILES): O=C(C1CCS(=O)(=O)CC1)N1CC[C@](c2ccc(C(F)(C(F)(F)F)C(F)(F)F)cc2)(S(=O)(=O)c2ccc(F)cc2)C1
InChIKey: ZOHVYFFYFCNUAZ-QFIPXVFZSA-N
Target: Nuclear receptor ROR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35398
Assay: Inverse agonist activity at human Gal4-fused RORalpha LBD (272 to 556 residues) expressed in human Jurkat cells measured after 18 hrs by steady-glo luciferase reporter gene assay
Measurement: EC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 633.58, ALogP 4.84, HBA 5, HBD 0, PSA 88.59, QED 0.35
Compound (SMILES): CCOc1cc2ncnc(Nc3ccc4c(cnn4Cc4ccccc4)c3)c2cc1NC(=O)/C=C/CN1CCN(C)CC1
InChIKey: RSEKNDZBPQNPGL-JXMROGBWSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Irreversible inhibition of full length human ERBB1 autophosphorylation transfected in EGF-stimulated mouse NIH/3T3 cells incubated for 2 hrs followed by stimulation with EGF for 10 mins
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 576.71, ALogP 4.91, HBA 9, HBD 2, PSA 100.44, QED 0.23
Compound (SMILES): COc1cc(OC)cc(N(CCO)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: YHGCMZIYHWHQKR-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 435.48, ALogP 2.63, HBA 9, HBD 2, PSA 105.76, QED 0.41
Compound (SMILES): O=C(Nc1ccccc1)N[C@H]1CC[C@H](CCN2CCN(c3nsc4ccccc34)CC2)CC1
InChIKey: LBCLWNAKMLUAKD-AQYVVDRMSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Receptor Binding Test: 1. Experimental Materials:(1) D2 receptor Cell Transfection:This experiment utilizes the plasmid vector containing the gene of D2 receptor protein for transfecting HEK293 cells by calcium phosphate transfection method. By culturing the transfected cells in culture medium containing G418 and selecting cell clones followed by radioligand binding test, a stable cell strain capable of expressing the D2 receptor protein stably is finally obtained.(2) Materials for the Receptor Binding Test:Isotopic ligand [3H] Spiperone (113.0 Ci/mmol) purchased from Sigma Corporation; (+) spiperone purchased from RBI Corporation; GF/B glassfiber filter purchased from Whatman Corporation; imported and subpackaged Tris; PPO and POPOP purchased from Shanghai No. 1 Reagent Factory; and fat-soluble scintillation fluid. Beckman LS-6500 multifunction liquid scintillation counter.2. Experimental Methods:    (1) Cells:HEK-293 cells are infected with the recombinant viruses containing various genes. 48-72 h later, receptor proteins are massively expressed on the membrane. The cells are centrifuged at 1000 rpm for 5 min, then the culture supernatant is discarded and the cell pellets are collected, preserved in refrigerator at −20° C., and resuspended with Tris-HCl reaction buffer (pH=7.5) before use.(2) Competitive Receptor Binding Test:The compound to be tested, the radioligand (20 μL for each) and the receptor protein (160 μL) are added to a reaction tube, wherein the compound to be tested and the positive drug both have the final concentration of 10 μmol/L.After being incubated in water bath at 30° C. for 50 min, the tube is immediately transferred to ice bath to stop the reaction. The mixture is subjected to rapid suction filtration through GF/C glassfiber filter on Millipore cell sample collector, washed with eluent (50 mM Tris-HCl, pH 7.5) (3 mL×3) and dried under microwave for 5-6 min. The filter is transferred to a centrifuge tube (0.5 mL), added with 500 μL fat-soluble scintillation fluid, left in the dark for over min, and counted to determine the radioactivity intensity. The percentage inhibition ratio for each compound to inhibit the isotopic ligand binding is calculated with the following equation:inhibition ratio (1%)=(total binding tube CPM−compound CPM)/(total binding tube CPM−non-specific binding tube CPM)×100%Each compound is tested in duplicate, and the tests are carried out independently twice.Compounds with an inhibition ratio of over 95% are subjected to the receptor binding test at a series of concentrations so as to determine half maximal inhibitory concentration (IC50, the concentration of the compound required for inhibiting 50% binding of [3H]-Spiperone to D2 receptor). Each concentration is tested in duplicate, and tests are carried out independently twice for each compound.
Measurement: Ki = 1.06 nM (pChEMBL 8.970000267028809)
Descriptors: MW 463.65, ALogP 5.19, HBA 5, HBD 2, PSA 60.5, QED 0.53
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3F)ncnc2cc1OCC1CN(C)C(C)(C)CO1
InChIKey: TUJFKJGLVWEALU-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 495.38, ALogP 5.32, HBA 7, HBD 1, PSA 68.74, QED 0.46
Compound (SMILES): CCOc1cc(N2CCN(C3CCN(CCF)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: UPVDFQQBOKAQNJ-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 775.88, ALogP 7.69, HBA 10, HBD 2, PSA 103.16, QED 0.13
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)[C@H]2CC[C@H](NC(C)C)CC2)c1
InChIKey: AHSYHYFTUKZLCI-HZCBDIJESA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 3801.89 nM (pChEMBL 5.420000076293945)
Descriptors: MW 500.65, ALogP 5.49, HBA 8, HBD 1, PSA 77.33, QED 0.34
Compound (SMILES): CCC#CC[C@H](C)[C@H](O)/C=C/[C@H]1CC(F)(F)C(=O)N1CCCCCCC(=O)O
InChIKey: ZSUOOBFOIDLLEI-GPVXIOJZSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Agonist activity at human EP2 receptor expressed in HEK293T/17 cells assessed as increase in intracellular cAMP level incubated for 30 mins by ELISA
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 399.48, ALogP 3.61, HBA 3, HBD 2, PSA 77.84, QED 0.32
Compound (SMILES): CCOc1cc(N2CCC(N3CCN(CCC(F)(F)F)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: XXFVZGIXAUHHPA-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 825.89, ALogP 8.67, HBA 10, HBD 2, PSA 103.16, QED 0.12
Compound (SMILES): FC(F)(F)Oc1ccc(CN2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: GBUTXEQZPUPFAH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
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 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 416.41, ALogP 3.88, HBA 6, HBD 1, PSA 71.34, QED 0.55
Compound (SMILES): COCc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: FDLLZBANGODCSO-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.52, ALogP 4.73, HBA 7, HBD 0, PSA 65.3, QED 0.4
Compound (SMILES): O=C(COc1ccc2cc(C(O)(C(F)(F)F)C(F)(F)F)c(O)cc2c1)Nc1ccc(-c2ccccc2)cc1
InChIKey: XXALRTLBNJQPFL-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12923
Assay: Inhibition of recombinant FAP1 (unknown origin) using pNPP as substrate by spectrophotometric method
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 535.44, ALogP 6.54, HBA 4, HBD 3, PSA 78.79, QED 0.25
Compound (SMILES): COc1ccc(-c2nc3ccccn3c2-c2ccnc(Nc3cccc(OCCN(C)C)c3)n2)cc1C(=O)Nc1c(F)cccc1F
InChIKey: BXXIOBDDCFIKNO-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 635.68, ALogP 6.68, HBA 9, HBD 2, PSA 105.91, QED 0.16
Compound (SMILES): COc1cc(N2CCC(CCS(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: IWWHGEYVMAYCBW-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 781.89, ALogP 7.71, HBA 11, HBD 2, PSA 140.05, QED 0.13
Compound (SMILES): CC(C)c1sc2c(c1CC(=O)Nc1nc(-c3ccc(C(F)(F)F)c(F)c3)cs1)c(=O)n(C)c(=O)n2C
InChIKey: ZLGGDXLEMLRCRT-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 540.56, ALogP 4.88, HBA 8, HBD 1, PSA 85.99, QED 0.37
Compound (SMILES): COc1cc(OC)cc(N(Cc2nc(OC)cc(OC)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: CDHUCXPNWMRKCW-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 513.56, ALogP 4.19, HBA 11, HBD 0, PSA 109.54, QED 0.28
Compound (SMILES): C[C@@H]1CN(c2sc(C3CC3)nc2-c2nc3ccccc3[nH]2)CCN1C(=O)Cn1cnc2cccnc21
InChIKey: NYCIVVXGRDGDMY-MRXNPFEDSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells by Q patch-clamp method
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 498.62, ALogP 4.05, HBA 8, HBD 1, PSA 95.83, QED 0.39
Compound (SMILES): C=CC(=O)Nc1cccc(-c2cnc3[nH]cc(-c4cccc(C)c4F)c3c2)c1
InChIKey: JEKGFKWIAUMDPD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Biochemical Inhibition Assay: 1H-pyrrolo[2,3-b]pyridine, 1H-pyrazolo[3,4-b]pyridine and 5H-pyrrolo[2,3-b]pyrazine series of compounds exhibited over >100 fold selective against Janus and TEC family of kinases except for the BMX and TXK it had activity of 30 and 45 nM respectively.
Measurement: IC50 = 72.4 nM (pChEMBL 7.139999866485596)
Descriptors: MW 371.42, ALogP 5.47, HBA 2, HBD 2, PSA 57.78, QED 0.47
Compound (SMILES): CCCCN1CCOC(COc2cc3ncnc(Nc4ccc(Cl)c(Cl)c4)c3cc2OC)C1
InChIKey: CHESBDRRLQCAEW-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 491.42, ALogP 5.57, HBA 7, HBD 1, PSA 68.74, QED 0.42
Compound (SMILES): CCCCC(CC#N)n1cc(-c2ncnc3[nH]ccc23)cn1
InChIKey: OFOSNWSCZOAXGX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Kinase Assay: The compounds of the invention were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50 was measured for each kinase in the 40 uL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for Jak1, 30 uM for Jak2 and 3 uM for Jak3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 294.36, ALogP 3.47, HBA 5, HBD 1, PSA 83.18, QED 0.75
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](Cc1ccc(CN)cc1)NC(=O)c1ccccc1)B(O)O
InChIKey: FSDWYLVZNOVGAG-OALUTQOASA-N
Target: Nonstructural protein 3 (SINGLE PROTEIN), Zika virus
UniProt: A0A024AXB9
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Zika NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Zika virus (strain PRVABC59) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 454.34
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1O[C@@H]1C[C@H]2OC[C@H](OC)[C@H]2O1
InChIKey: HOAMTMPJKDREOY-ANULTFPQSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: Inhibition of recombinant human N-terminal GST-tagged factor 10a cleavage site-fused Flt1 (K784 to I1338 residues) expressed in baculovirus infected insect Sf9 cells using poly-EY as substrate after 120 mins in presence of gamma33P-ATP by liquid scintillation spectrometry
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 478.33, ALogP 4.6, HBA 8, HBD 1, PSA 83.96, QED 0.55
Compound (SMILES): N#Cc1cc(C(F)(F)F)ccc1N1CCOc2c1ccc(S(=O)(=O)Nc1nccs1)c2F
InChIKey: USUJTFJOBUIIHB-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: In Vitro Assay: HEK 293 cells stably transfected with either Nav 1.7 or with Nav 1.5 were recorded in population patch-clamp mode with the IonWorks® Quattro automated electrophysiology system in accordance with the manufacturer's specifications (Molecular Devices, LLC, Sunnyvale, Calif.). Sodium channel currents were measured in response to a train of depolarizations that induced successively greater inactivation. Cells were held at −110 mV for three seconds (Nav 1.7) or half a second (Nav 1.5) from a holding voltage of −15 mV, then put through a series of 26 pulses of 150 msec duration to −20 mV at a frequency of 5 Hz. Cells were then left unclamped for a period of 3 to 8 minutes while a single concentration of test compound was added. Cells were then reclamped and put through the same voltage protocol. Current at the end of the 26th pulse to −20 mV was subtracted from the peak current evoked by the 26th pulse to −20 mV to correct for leak current.
Measurement: IC50 = 5730 nM (pChEMBL 5.239999771118164)
Descriptors: MW 484.46, ALogP 4.5, HBA 7, HBD 1, PSA 95.32, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(CCNS(=O)(=O)N(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: SISPBNWXCLKBKE-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 511.61, ALogP 2.58, HBA 9, HBD 1, PSA 114.71, QED 0.35