lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C1NCC2(CCCCC2)n2c1cc1cnc(Nc3ccc(C(=O)N4CCNCC4)cc3)nc12
InChIKey: BKCOGSHTNWTZNI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: CDK Inhibition In Vitro Assay: Selected compounds disclosed herein were tested in kinase assays by Nanosyn (Santa Clara, Calif.) to determine their inhibitory effect on these CDKs. The assays were performed using microfluidic kinase detection technology (Caliper Assay Platform). The compounds were tested in 12-point dose-response format in singlicate at Km for ATP. Specifics of each assay are as described below:CDK1/Cyclin B1: Enzyme concentration: 0.08 nM; ATP concentration: 40 μM; Incubation time: 3 hr. CDK2/Cyclin A: Enzyme concentration: 0.1 nM; ATP concentration: 50 μM; Incubation time: 3 hr. CDK2/Cyclin E: Enzyme concentration: 0.15 nM; ATP concentration: 100 μM; Incubation time: 3 hr. CDK4/Cyclin D1: Enzyme concentration: 1 nM; ATP concentration: 200 μM; Incubation time: 3 hr. CDK6/Cyclin D3: Enzyme concentration: 2 nM; ATP concentration: 300 μM; Incubation time: 3 hr. CDK9/Cyclin T1: Enzyme concentration: 5 nM; ATP concentration: 10 μM; Incubation time: 17 hr.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 459.55, ALogP 2.62, HBA 7, HBD 3, PSA 104.18, QED 0.56
Compound (SMILES): Cn1c(=O)n(CC(=O)NC2CC(F)(F)C2)c2cc(-c3cccc(C(F)(F)F)c3)cnc21
InChIKey: KFSQZOFWXRWXDQ-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: Biological Assay (standard): NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.5 mM MgCl2, 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to ~EC40 used to maximize the assay's signal window and ability to detect NMDA receptor antagonists and negative allosteric modulators. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 174 nM (pChEMBL 6.760000228881836)
Descriptors: MW 440.37, ALogP 3.33, HBA 5, HBD 1, PSA 68.92, QED 0.63
Compound (SMILES): CCN1CC2(C1)CN(c1ccc(Nc3ncc(F)c(-c4cc5c(=O)n(C)nc(C6CN(C(=O)OC(C)(C)C)C6)c5s4)n3)nc1)C2
InChIKey: WFRGJVMNASTFDG-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00534
Assay: CDK6/CyclinD1 Enzymatic Activity Assay: The inhibitory activity of compounds was evaluated in vitro using TR-FRET assay with white 384-well low volume microplate (Greiner Bio-One). CDK6/Cyclin D1 catalyzed phosphorylation of peptide in the presence and absence of compounds was measured and used in IC50 determination. Recombinant protein complex CDK6/Cyclin D1, expressed from insect cell, was purchased from ProQinase. Testing compounds were dissolved in DMSO at 0.1 mM and tested in 9-dose IC50 mode. The reaction mixture was prepared by mixing CDK6/Cyclin D1 (1 nM final), ULight-4E-BP1 (100 nM final, Perkinelmer, TRF0128-D), and ATP (250 uM final) in assay buffer (20 mM of HEPES pH 7.4, 1 mM of EGTA, 0.05% BSA, 0.005% Tween 20, and 1 mM TCEP). The compound of interest in DMSO was added to each well in 3-fold serial dilution by dispenser (TECAN D300E). After 20 minutes preincubation at room temperature, 0.1 uL MgCl2 (10 mM final) was added to initiate the reaction. Following a 60 minutes incubation at 37 C., the reaction was stopped by addition of 2 uL of quenching buffer consisting of Lance detection buffer (Perkinelmer CR97-100C), 2 nM LANCE Ultra Europium-anti-P-4E-BP1 (Perkinelmer, TRF0216-D), 10 mM EDTA, and incubate at room temperature for additional 60 minutes in dark. The reaction signal was measured by Envision multimode plate reader (PerkinElmer, 2102-0010). IC50 values were determined by fitting the data to the standard 4 parameters with Hill Slope using GraphPad Prism software.
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 633.75, ALogP 4.21, HBA 12, HBD 1, PSA 121.61, QED 0.33
Compound (SMILES): Cc1cc2cnc(NC3CCN(S(=O)(=O)NC[C@@H]4CCCO4)CC3)nc2n([C@H]2CCC[C@]2(C)O)c1=O
InChIKey: ZAFRFGKCOSNMCP-SKPFHBQLSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00534
Assay: CDK6/Cyclin D1 Mobility Shift Assay: The purpose of the CDK6/Cyclin D1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) in the presence of small molecule inhibitors by using a fluorescence based microfluidic mobility shift assay. CDK6/Cyclin D1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide 5-FAM-Dyrktide (5-FAM-RRRFRPASPLRGPPK) (SEQ ID NO:2). The mobility shift assay electrophoretically separates the fluorescently labeled peptides (substrate and phosphorylated product) following the kinase reaction. Both substrate and product are measured and the ratio of these values is used to generate % conversion of substrate to product by the LabChip EZ Reader. Typical reaction solutions contained 2% DMSO (± inhibitor), 10 mM MgCl2, 1 mM DTT, 2 mM ATP, 0.005% Tween 20 (TW-20), 3 μM 5-FAM-Dyrktide, 3 nM (active sites) CDK6/Cyclin D1 in 40 mM HEPES buffer at pH 7.5.Inhibitor Ki determinations for non-phosphorylated CDK6/CyclinD1 (LJIC-2003A2/1865) were initiated with the addition of ATP (50 μL final reaction volume), following a twelve minute pre-incubation of enzyme and inhibitor at 22° C. in the reaction mix. The reaction was stopped after 35 minutes by the addition of 50 μL of 25 mM EDTA. Ki determinations were made from a plot of the fractional velocity as a function of inhibitor concentration fit to the Morrison equation with the enzyme concentration as a variable.
Measurement: Ki = 23.5 nM (pChEMBL 7.630000114440918)
Descriptors: MW 520.66, ALogP 1.47, HBA 9, HBD 3, PSA 138.68, QED 0.5
Compound (SMILES): O=c1[nH]c2ncc(-c3cccs3)cc2n1CC1CC1
InChIKey: IBXUFNNVUMHHRO-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: Biological Assay (standard): NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.5 mM MgCl2, 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to ~EC40 used to maximize the assay's signal window and ability to detect NMDA receptor antagonists and negative allosteric modulators. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 1556 nM (pChEMBL 5.809999942779541)
Descriptors: MW 271.35, ALogP 2.86, HBA 4, HBD 1, PSA 50.68, QED 0.8
Compound (SMILES): Cc1cc(C(=O)N[C@@H]2CCC[C@H](C(=O)Nc3cc(-c4cc(F)c5nn(C)c(C(C)C)c5c4)c(C)cn3)C2)no1
InChIKey: YGXSGRGRLJSQDK-AZUAARDMSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: CDK4/CyclinD1 Enzymatic Activity Assay: The inhibitory activity of compounds was evaluated in vitro using TR-FRET assay with white 384-well low volume microplate (Greiner Bio-One). CDK4/Cyclin D1 catalyzed phosphorylation of peptide in the presence and absence of compounds was measured and used in IC50 determination. Recombinant protein complex CDK4/Cyclin D1, expressed from insect cell, was purchased from ProQinase. Testing compounds were dissolved in DMSO at 1 mM and tested in 9-dose IC50 mode. The reaction mixture was prepared by mixing CDK4/CyclinD1 (1 nM final), ULight-4E-BP1 (100 nM final, Perkinelmer, TRF0128-D), and ATP (2 mM final) in assay buffer (20 mM of HEPES pH 7.4, 1 mM of EGTA, 0.05% BSA, 0.005% Tween 20, and 1 mM TCEP). The compound of interest in DMSO was added to each well in 3-fold serial dilution by dispenser (TECAN D300E) to make a 9.9 μL of reaction mixture. After 20 minutes preincubation at room temperature, 0.1 μL MgCl2(10 mM final) was added to initiate the reaction. Following a 45 minutes incubation at 37° C., the reaction was stopped by addition of 2 μL of quenching buffer consisting of Lance detection buffer (Perkinelmer CR97-100C), LANCE Ultra Europium-anti-P-4E-BP1 (Perkinelmer, TRF0216-D), EDTA, and incubate at room temperature for additional 60 minutes in dark. The reaction signal was measured by Envision multimode plate reader (PerkinElmer, 2102-0010).
Measurement: IC50 = 2.93 nM (pChEMBL 8.529999732971191)
Descriptors: MW 532.62, ALogP 5.43, HBA 7, HBD 2, PSA 114.94, QED 0.34
Compound (SMILES): CN(C)C1CCN(c2ccc(Nc3ncc(F)c(-c4cc(F)c5nc6n(c5c4)C(C)(C)CC6)n3)nc2)CC1
InChIKey: FWPHUFSCXZZXFS-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00534
Assay: Inhibition Assay: In vitro inhibition of CDK (CDK1, CDK4, CDK6) activity by compounds of the present invention was tested by the following method.1. Preparation of kinase reaction buffer I: 5× Reaction Buffer A (Promega; V307A-C) provided in the kit was diluted with a mixture of Milli Q H2O and 0.1M DTT (dithiothreitol) to 4× kinase buffer; then Milli Q H2O was added in a proper proportion, to finally formulate into 1× kinase buffer.Preparation of kinase reaction buffer II: 0.5% DMSO (dimethyl sulfoxide) was added into 1× kinase reaction buffer and uniformly mixed to obtain the title buffer.2. Preparation of kinase solution: 100 ng/μl kinase stock solution was formulated with 1× kinase reaction buffer into kinase solution with the desired concentration for each reaction system.3. Preparation of solution of test compound and LY2835219 as a control:(1) Preparation of Solution of LY2835219 as a Controla. 1 μl of 10 mM standard stock solution was added respectively into 9 μl of kinase reaction buffer I and uniformly mixed; then 90 μl of kinase reaction buffer I was added and uniformly mixed; and then 100 μl of kinase reaction buffer I was added and uniformly mixed, to achieve a final concentration of 50 μM.b. 40 μl of kinase reaction buffer II was added into Well B2-B10 of a 96-well plate; and 50 μl of above-mentioned solution was added into Well B1;c. 10 μl of solution was taken from Well B1, added into Well B2 and uniformly mixed, then 10 μl of dilution was taken from Well B2 and added into Well B3, the serial dilution was continued up to B9, to obtain 5-fold serial dilutions of the reference solution.
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 518.62, ALogP 5.12, HBA 8, HBD 1, PSA 75, QED 0.39
Compound (SMILES): COc1ccccc1-c1cc(Nc2ccc([N+](=O)[O-])c(F)c2)ncn1
InChIKey: NGBHCPBYCZJVND-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: In Vitro CDK9/CyclinT Assay: The activity of the compounds described in the present invention can be determined by measuring the phosphorylation of a fluorescently-labeled peptide by human CDK9/CyclinT kinase complex by fluorescent polarization using a commercially available IMAP Screening Express Assay Kit (Molecular devices).Test compounds were diluted in 100% DMSO to 5 mM stock concentration, then further dilutions were made in H2O or 100% DMSO to desirable concentrations.Each reaction consisted of 5 nM enzyme: CDK9/CyclinT (Proqinase cat#0371-0345-1), 400 nM TAMRA-Rbtide (synthetic 15-mer peptide derived from human retinoblastoma tumor suppressor protein labeled with TAMRA dye, Genecust Europe), 12 μM ATP (=Kmapp, Sigma-Aldrich) and kinase buffer: 20 mM MOPS pH 7 (Sigma-Aldrich), 1 mM DTT (Sigma-Aldrich), 10 mM MgCl2 (Sigma-Aldrich), 0.01% Tween 20 (Sigma-Aldrich).For each reaction, 4 or 6 μl containing TAMRA-Rbtide, ATP and kinase buffer were combined with 2 μl diluted compound in H2O or 0.028 μl compound in 100% DMSO. The kinase reaction was started by the addition of 2 μl diluted enzyme. The reaction was allowed to run for 1 hour at room temperature. The reaction was stopped by adding 15 μl IMAP beads (1:400 beads in progressive (100% buffer A) 1× buffer). After an additional 1 hour, fluorescent polarization (Ex: 550-10 nm, Em: 590-10 nm, Dich: 561 nm) was measured using an Analyst GT (Molecular devices).
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 340.31, ALogP 3.94, HBA 6, HBD 1, PSA 90.18, QED 0.56
Compound (SMILES): COc1ccccc1-c1cc(Nc2cccc(NS(C)(=O)=O)c2)ncn1
InChIKey: GZMVECPBSUHMMJ-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00534
Assay: Inhibition of CDK6/Cyclin D3 (unknown origin) using ULight MBP peptide as substrate in presence of ATP incubated for 1 hr by FRET based LANCE Ultra KinaSelect screen assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 370.43, ALogP 3.27, HBA 6, HBD 2, PSA 93.21, QED 0.69
Compound (SMILES): O=C1NCC2(CCCCC2)n2c1cc1cnc(Nc3ccc(C(=O)N4CCNCC4)cc3)nc12
InChIKey: BKCOGSHTNWTZNI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: CDK Inhibition In Vitro Assay: Selected compounds disclosed herein were tested in kinase assays by Nanosyn (Santa Clara, Calif.) to determine their inhibitory effect on these CDKs. The assays were performed using microfluidic kinase detection technology (Caliper Assay Platform). The compounds were tested in 12-point dose-response format in singlicate at Km for ATP. Specifics of each assay are as described below:CDK1/Cyclin B1: Enzyme concentration: 0.08 nM; ATP concentration: 40 μM; Incubation time: 3 hr. CDK2/Cyclin A: Enzyme concentration: 0.1 nM; ATP concentration: 50 μM; Incubation time: 3 hr. CDK2/Cyclin E: Enzyme concentration: 0.15 nM; ATP concentration: 100 μM; Incubation time: 3 hr. CDK4/Cyclin D1: Enzyme concentration: 1 nM; ATP concentration: 200 μM; Incubation time: 3 hr. CDK6/Cyclin D3: Enzyme concentration: 2 nM; ATP concentration: 300 μM; Incubation time: 3 hr. CDK9/Cyclin T1: Enzyme concentration: 5 nM; ATP concentration: 10 μM; Incubation time: 17 hr.
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 459.55, ALogP 2.62, HBA 7, HBD 3, PSA 104.18, QED 0.56
Compound (SMILES): Cc1ccc([C@@H](C)NC(=O)c2cc(OC[C@H]3CCOC3)cc(-c3ncc(C4CCC4)s3)c2)nn1
InChIKey: KRMAXJMLJAVOGJ-MSOLQXFVSA-N
Target: P2X2/P2X3 heterotrimeric receptor (PROTEIN COMPLEX), Homo sapiens
UniProt: P56373
Assay: Biological Assay: A fluorescent imaging plate reader (FILEX/FLIPR station; Molecular Devices) was used to monitor intracellular calcium levels using the calcium-chelating dye Rim-4 (Molecular Probes). The excitation and emission wavelengths used to monitor fluorescence were 470-495 nm and 515-575 nm, respectively. Cells expressing purinergic receptors P2X3 (human) or P2X2/3 (human) were plated at a density of 15,000 cells/well in collagen-coated 384-well plates approximately 20 hours before beginning the assay. On the day of the assay, 20 μl of loading buffer (Hank's balanced salt solution, 20 mM HEPES, 0.5 mM CaCl2, 0.5 mM MgCl2, 0.1% BSA, 5 mM probenecid, 10 mM D-glucose monohydrate, 2 μM Fluo-4, and 5 units/mL, hexokinase, pH=7.4) was added and cells dye-loaded for 90 min at 37° C. The dye supernatant was removed and replaced with 45 μl probenecid buffer (Hank's balanced salt solution, 20 mM HEPES, 0.5 mM CaCl2, 0.5 mM MgCl2, 0.1% BSA, 5 mM probenecid, 10 mM D-glucose monohydrate, pH=7.4). The test compound was added in a volume of 5 μl and allowed to incubate for 30 min at 37° C.
Measurement: IC50 = 209 nM (pChEMBL 6.679999828338623)
Descriptors: MW 478.62, ALogP 5.08, HBA 7, HBD 1, PSA 86.23, QED 0.49
Compound (SMILES): CN1CCc2c(c3ccccc3n2Cc2ccc(C(=O)NO)cc2)C1.O=C(O)C(F)(F)F
InChIKey: AVAOVICSJJIYRZ-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human HDAC3/NcoR2 using fluorogenic RHKKAc peptide as substrate by fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 335.41, ALogP 2.8, HBA 4, HBD 2, PSA 57.5, QED 0.57
Compound (SMILES): COc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/CN(C)C
InChIKey: ZHGLJJSISHRVHL-SOFGYWHQSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of recombinant CDK4/cyclin D1 (unknown origin) using protein as substrate
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 543.03, ALogP 5.54, HBA 8, HBD 2, PSA 112.4, QED 0.25
Compound (SMILES): COc1ccccc1-c1cc(Nc2cccc(NS(C)(=O)=O)c2)ncn1
InChIKey: GZMVECPBSUHMMJ-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using ULight MBP peptide as substrate in presence of ATP incubated for 1 hr by FRET based LANCE Ultra KinaSelect screen assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 370.43, ALogP 3.27, HBA 6, HBD 2, PSA 93.21, QED 0.69
Compound (SMILES): COc1ccc(-n2nc(C(F)(F)F)c3c2C(=O)N(C2CCN(N4CCCCC4=O)CC2)CC3)cc1
InChIKey: YFPMFJCXOLJIOD-UHFFFAOYSA-N
Target: Coagulation factor V/Coagulation factor X/Serine/threonine-protein kinase BRSK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P00742
Assay: In Vitro Assay: Prothrombinase Assay:The effect of test compounds on prothrombinase activity is measured via thrombin generation. Briefly, 12.5 μL human factor Xa is incubated in 10 mM HEPES buffer, pH 7.4, 2 mM CaCl2, the final concentration is 0.5 nM, and add 12.5 μL human platelets (1×107 mL−1) for 10 minutes at 37° C. The reaction is initiated by adding 25 μL prothrombin, the final concentration is 0.5 μM and 2 μL the assay buffer containing 2% (V/V) DMSO (uninhibited control) or various concentrations of the compounds to be tested diluted in the assay buffer containing 2% (V/V) DMSO. After 20 minutes, thrombin activity is measured by adding 48 μL substrate of S-2238 (Chromogenix) at the final concentration is 50 μM.
Measurement: Ki < 10 nM (pChEMBL 8)
Descriptors: MW 491.51, ALogP 3.29, HBA 6, HBD 0, PSA 70.91, QED 0.66
Compound (SMILES): O=C1NCC2(CCCCC2)n2c1cc1cnc(Nc3ccc(C(=O)N4CCNCC4)cc3)nc12
InChIKey: BKCOGSHTNWTZNI-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q00534
Assay: CDK Inhibition In Vitro Assay: Selected compounds disclosed herein were tested in kinase assays by Nanosyn (Santa Clara, Calif.) to determine their inhibitory effect on these CDKs. The assays were performed using microfluidic kinase detection technology (Caliper Assay Platform). The compounds were tested in 12-point dose-response format in singlicate at Km for ATP. Specifics of each assay are as described below:CDK1/Cyclin B1: Enzyme concentration: 0.08 nM; ATP concentration: 40 μM; Incubation time: 3 hr. CDK2/Cyclin A: Enzyme concentration: 0.1 nM; ATP concentration: 50 μM; Incubation time: 3 hr. CDK2/Cyclin E: Enzyme concentration: 0.15 nM; ATP concentration: 100 μM; Incubation time: 3 hr. CDK4/Cyclin D1: Enzyme concentration: 1 nM; ATP concentration: 200 μM; Incubation time: 3 hr. CDK6/Cyclin D3: Enzyme concentration: 2 nM; ATP concentration: 300 μM; Incubation time: 3 hr. CDK9/Cyclin T1: Enzyme concentration: 5 nM; ATP concentration: 10 μM; Incubation time: 17 hr.
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 459.55, ALogP 2.62, HBA 7, HBD 3, PSA 104.18, QED 0.56
Compound (SMILES): COc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/CN(C)C
InChIKey: ZHGLJJSISHRVHL-SOFGYWHQSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of recombinant CDK2/cyclin E (unknown origin) using protein as substrate
Measurement: IC50 > 18000 nM (pChEMBL 4.744999885559082)
Descriptors: MW 543.03, ALogP 5.54, HBA 8, HBD 2, PSA 112.4, QED 0.25
Compound (SMILES): COc1ccccc1-c1cc(Nc2cccc(NS(C)(=O)=O)c2)ncn1
InChIKey: GZMVECPBSUHMMJ-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using ULight MBP peptide as substrate in presence of ATP incubated for 1 hr by FRET based LANCE Ultra KinaSelect screen assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 370.43, ALogP 3.27, HBA 6, HBD 2, PSA 93.21, QED 0.69
Compound (SMILES): O=C1NCC2(CCCCC2)n2c1cc1cnc(Nc3ccc(C(=O)N4CCNCC4)cc3)nc12
InChIKey: BKCOGSHTNWTZNI-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: CDK Inhibition In Vitro Assay: Selected compounds disclosed herein were tested in kinase assays by Nanosyn (Santa Clara, Calif.) to determine their inhibitory effect on these CDKs. The assays were performed using microfluidic kinase detection technology (Caliper Assay Platform). The compounds were tested in 12-point dose-response format in singlicate at Km for ATP. Specifics of each assay are as described below:CDK1/Cyclin B1: Enzyme concentration: 0.08 nM; ATP concentration: 40 μM; Incubation time: 3 hr. CDK2/Cyclin A: Enzyme concentration: 0.1 nM; ATP concentration: 50 μM; Incubation time: 3 hr. CDK2/Cyclin E: Enzyme concentration: 0.15 nM; ATP concentration: 100 μM; Incubation time: 3 hr. CDK4/Cyclin D1: Enzyme concentration: 1 nM; ATP concentration: 200 μM; Incubation time: 3 hr. CDK6/Cyclin D3: Enzyme concentration: 2 nM; ATP concentration: 300 μM; Incubation time: 3 hr. CDK9/Cyclin T1: Enzyme concentration: 5 nM; ATP concentration: 10 μM; Incubation time: 17 hr.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 459.55, ALogP 2.62, HBA 7, HBD 3, PSA 104.18, QED 0.56
Compound (SMILES): Cc1ccc([C@@H](C)NC(=O)c2cc(OC[C@H]3CCOC3)cc(-c3ncc(C4CCC4)s3)c2)nn1
InChIKey: KRMAXJMLJAVOGJ-MSOLQXFVSA-N
Target: P2X2/P2X3 heterotrimeric receptor (PROTEIN COMPLEX), Homo sapiens
UniProt: P56373
Assay: Biological Assay: A fluorescent imaging plate reader (FILEX/FLIPR station; Molecular Devices) was used to monitor intracellular calcium levels using the calcium-chelating dye Rim-4 (Molecular Probes). The excitation and emission wavelengths used to monitor fluorescence were 470-495 nm and 515-575 nm, respectively. Cells expressing purinergic receptors P2X3 (human) or P2X2/3 (human) were plated at a density of 15,000 cells/well in collagen-coated 384-well plates approximately 20 hours before beginning the assay. On the day of the assay, 20 μl of loading buffer (Hank's balanced salt solution, 20 mM HEPES, 0.5 mM CaCl2, 0.5 mM MgCl2, 0.1% BSA, 5 mM probenecid, 10 mM D-glucose monohydrate, 2 μM Fluo-4, and 5 units/mL, hexokinase, pH=7.4) was added and cells dye-loaded for 90 min at 37° C. The dye supernatant was removed and replaced with 45 μl probenecid buffer (Hank's balanced salt solution, 20 mM HEPES, 0.5 mM CaCl2, 0.5 mM MgCl2, 0.1% BSA, 5 mM probenecid, 10 mM D-glucose monohydrate, pH=7.4). The test compound was added in a volume of 5 μl and allowed to incubate for 30 min at 37° C.
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 478.62, ALogP 5.08, HBA 7, HBD 1, PSA 86.23, QED 0.49
Compound (SMILES): COc1cc2ncc(C#N)c(Nc3ccc(OCc4ccccn4)c(Cl)c3)c2cc1NC(=O)/C=C/CN(C)C
InChIKey: ZHGLJJSISHRVHL-SOFGYWHQSA-N
Target: Cyclin-dependent kinase 1/cyclin B1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P14635
Assay: Inhibition of recombinant CDK1/cyclin B1 (unknown origin) using protein as substrate
Measurement: IC50 > 18000 nM (pChEMBL 4.744999885559082)
Descriptors: MW 543.03, ALogP 5.54, HBA 8, HBD 2, PSA 112.4, QED 0.25
Compound (SMILES): COc1cc2nc(C)nc(NC(C)c3ccc(-c4cnc5n4CCC5)s3)c2cc1OC
InChIKey: XRGDXPBYPNBGJI-UHFFFAOYSA-N
Target: SOS1-KRAS (PROTEIN COMPLEX), Homo sapiens
UniProt: Q07889
Assay: Inhibition of N-terminal GST-tagged recombinant human KRAS G12C mutant (1 to 169 residues) expressed in Escherichia coli/N-terminal His10-tagged wild-type recombinant human SOS1 catalytic domain (564 to 1049 residues) expressed in Escherichia coli protein-protein interaction preincubated for 2 mins with KRAS followed by SOS1 addition measured after 60 mins in presence of anti-6His-XL665 by HTRF analysis
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 435.55, ALogP 5, HBA 8, HBD 1, PSA 74.09, QED 0.46
Compound (SMILES): COc1ccccc1-c1cc(Nc2cccc(NS(C)(=O)=O)c2)ncn1
InChIKey: GZMVECPBSUHMMJ-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Displacement of kinase tracer 236 from CDK7/Cyclin H/MAT1 (unknown origin) assessed as dissociation constant incubated for 1 hr by LanthScreen Eu kinase binding assay
Measurement: Kd = 15990 nM (pChEMBL 4.800000190734863)
Descriptors: MW 370.43, ALogP 3.27, HBA 6, HBD 2, PSA 93.21, QED 0.69
Compound (SMILES): COc1ccccc1-c1cc(Nc2cccc(NS(C)(=O)=O)c2)ncn1
InChIKey: GZMVECPBSUHMMJ-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Displacement of kinase tracer 236 from CDK9/Cyclin T1 (unknown origin) assessed as dissociation constant incubated for 1 hr by LanthScreen Eu kinase binding assay
Measurement: Kd = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 370.43, ALogP 3.27, HBA 6, HBD 2, PSA 93.21, QED 0.69
Compound (SMILES): C[C@H]1Oc2cc(cnc2N)-c2c(nn(C)c2C#N)CN(C)C(=O)C2C=CC(F)=CC21
InChIKey: VXYZCOCRVAQWBG-VCANKDNSSA-N
Target: SLC34A2-ROS1 (CHIMERIC PROTEIN), Homo sapiens
UniProt: O95436
Assay: Inhibition of SLC34A2-ROS1 fusion protein expressed in human HCC78 cells assessed as inhibition of phosphorylated ROS1 incubated for 1 hr by ELISA analysis
Measurement: IC50 = 0.19 nM (pChEMBL 9.720000267028809)
Descriptors: MW 408.44, ALogP 2.33, HBA 7, HBD 1, PSA 110.06, QED 0.72
Compound (SMILES): C[C@H]1Oc2cc(cnc2N)-c2c(nn(C)c2C#N)CN(C)C(=O)C2C=CC(F)=CC21
InChIKey: VXYZCOCRVAQWBG-VCANKDNSSA-N
Target: H-2 class II histocompatibility antigen gamma chain/Proto-oncogene tyrosine-protein kinase ROS (CHIMERIC PROTEIN), Mus musculus
UniProt: P04441
Assay: Inhibition of CD74-ROS1 expressed in mouse BaF3 cells assessed as inhibition of phosphorylated ROS1 incubated for 1 hr by ELISA analysis
Measurement: IC50 = 0.23 nM (pChEMBL 9.640000343322754)
Descriptors: MW 408.44, ALogP 2.33, HBA 7, HBD 1, PSA 110.06, QED 0.72
Compound (SMILES): C[C@H]1Oc2cc(cnc2N)-c2c(nn(C)c2C#N)CN(C)C(=O)C2C=CC(F)=CC21
InChIKey: VXYZCOCRVAQWBG-VCANKDNSSA-N
Target: H-2 class II histocompatibility antigen gamma chain/Proto-oncogene tyrosine-protein kinase ROS (CHIMERIC PROTEIN), Mus musculus
UniProt: P04441
Assay: Inhibition of CD74-ROS1 expressed in mouse NIH3T3 cells assessed as inhibition of phosphorylated ROS1 incubated for 1 hr by ELISA analysis
Measurement: IC50 = 0.53 nM (pChEMBL 9.279999732971191)
Descriptors: MW 408.44, ALogP 2.33, HBA 7, HBD 1, PSA 110.06, QED 0.72
Compound (SMILES): C[C@H]1Oc2cc(cnc2N)-c2c(nn(C)c2C#N)CN(C)C(=O)C2C=CC(F)=CC21
InChIKey: VXYZCOCRVAQWBG-VCANKDNSSA-N
Target: Golgi-associated PDZ and coiled-coil motif-containing protein/Proto-oncogene tyrosine-protein kinase ROS (CHIMERIC PROTEIN), Mus musculus
UniProt: Q8BH60
Assay: Inhibition of FIG-ROS1 short isoform fusion protein expressed in mouse NIH3T3 cells assessed as inhibition of phosphorylated ROS1 incubated for 1 hr by ELISA analysis
Measurement: IC50 = 0.24 nM (pChEMBL 9.619999885559082)
Descriptors: MW 408.44, ALogP 2.33, HBA 7, HBD 1, PSA 110.06, QED 0.72
Compound (SMILES): C[C@H]1Oc2cc(cnc2N)-c2c(nn(C)c2C#N)CN(C)C(=O)C2C=CC(F)=CC21
InChIKey: VXYZCOCRVAQWBG-VCANKDNSSA-N
Target: Golgi-associated PDZ and coiled-coil motif-containing protein/Proto-oncogene tyrosine-protein kinase ROS (CHIMERIC PROTEIN), Mus musculus
UniProt: Q8BH60
Assay: Inhibition of FIG-ROS1 long isoform fusion protein expressed in mouse NIH3T3 cells assessed as inhibition of phosphorylated ROS1 incubated for 1 hr by ELISA analysis
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 408.44, ALogP 2.33, HBA 7, HBD 1, PSA 110.06, QED 0.72
Compound (SMILES): COc1ccccc1-c1cc(Nc2cccc(NS(C)(=O)=O)c2)ncn1
InChIKey: GZMVECPBSUHMMJ-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using ULight MBP peptide as substrate in presence of ATP incubated for 1 hr by FRET based LANCE Ultra KinaSelect screen assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 370.43, ALogP 3.27, HBA 6, HBD 2, PSA 93.21, QED 0.69
Compound (SMILES): COc1ccc(-n2nc(C(F)(F)F)c3c2C(=O)N(C2CCN(N4CCCCC4=O)CC2)CC3)cc1
InChIKey: YFPMFJCXOLJIOD-UHFFFAOYSA-N
Target: Coagulation factor V/Coagulation factor X/Serine/threonine-protein kinase BRSK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P12259
Assay: In Vitro Assay: Prothrombinase Assay:The effect of test compounds on prothrombinase activity is measured via thrombin generation. Briefly, 12.5 μL human factor Xa is incubated in 10 mM HEPES buffer, pH 7.4, 2 mM CaCl2, the final concentration is 0.5 nM, and add 12.5 μL human platelets (1×107 mL−1) for 10 minutes at 37° C. The reaction is initiated by adding 25 μL prothrombin, the final concentration is 0.5 μM and 2 μL the assay buffer containing 2% (V/V) DMSO (uninhibited control) or various concentrations of the compounds to be tested diluted in the assay buffer containing 2% (V/V) DMSO. After 20 minutes, thrombin activity is measured by adding 48 μL substrate of S-2238 (Chromogenix) at the final concentration is 50 μM.
Measurement: Ki < 10 nM (pChEMBL 8)
Descriptors: MW 491.51, ALogP 3.29, HBA 6, HBD 0, PSA 70.91, QED 0.66
Compound (SMILES): COc1ccccc1-c1cc(Nc2cccc(NS(C)(=O)=O)c2)ncn1
InChIKey: GZMVECPBSUHMMJ-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Displacement of kinase tracer 236 from CDK7/Cyclin H/MAT1 (unknown origin) assessed as dissociation constant incubated for 1 hr by LanthScreen Eu kinase binding assay
Measurement: Kd = 15990 nM (pChEMBL 4.800000190734863)
Descriptors: MW 370.43, ALogP 3.27, HBA 6, HBD 2, PSA 93.21, QED 0.69
Compound (SMILES): Cc1c(-c2ccccc2)cccc1N1C(=O)c2ccc(CN3CCOCC3)cc2C1=O
InChIKey: BFEWUGJOFOJDRG-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of europium-labeled PD-1/biotinylated PD-L1 interaction (unknown origin) preincubated for 15 mins with PD-L1 followed by PD-1 addition and measured after 90 mins by TR-FRET assay
Measurement: IC50 = 2519 nM (pChEMBL 5.599999904632568)
Descriptors: MW 412.49, ALogP 4.29, HBA 4, HBD 0, PSA 49.85, QED 0.6
Compound (SMILES): CN(C)C(=O)[C@@H](NC(=O)c1ccccc1-c1ccc(C(F)(F)F)cc1)c1ccc(Cl)c(C(F)(F)F)c1
InChIKey: VYIYNRXUUXEPDX-NRFANRHFSA-N
Target: NKGD2-MICA (PROTEIN COMPLEX), Homo sapiens
UniProt: P26718
Assay: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 528.88, ALogP 6.6, HBA 2, HBD 1, PSA 49.41, QED 0.38
Compound (SMILES): Cc1n[nH]c2ccc(-c3nnc4n3[C@H](c3ccc(Cl)cc3)CNC4)cc12
InChIKey: DXZXMWGMIHOZIS-KRWDZBQOSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P49336
Assay: Inhibition of His tagged human recombinant CDK8/Cyclin C expressed in baculovirus expression system incubated for 15 mins by FRET-based LanthaScreen binding competition assay
Measurement: IC50 = 0.48 nM (pChEMBL 9.319999694824219)
Descriptors: MW 364.84, ALogP 3.48, HBA 5, HBD 2, PSA 71.42, QED 0.57
Compound (SMILES): Clc1cc(-c2cn(Cc3cn4cc(CNCC5CCC5)ccc4n3)nn2)c2cn[nH]c2c1
InChIKey: DLXPJWPAKWEJKT-UHFFFAOYSA-N
Target: METTL3/METTL14 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5'P-uacacucgaucuggacuaaagcugcuc-3' and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis
Measurement: IC50 = 4.35 nM (pChEMBL 8.359999656677246)
Descriptors: MW 446.95, ALogP 4.06, HBA 7, HBD 2, PSA 88.72, QED 0.39
Compound (SMILES): Cc1c(COc2ccc(CN[C@H](CO)C(=O)O)c(OCc3cccc(C#N)c3)c2)cccc1-c1ccc2c(c1)OCCO2
InChIKey: SLWLHSUYZWZGEI-SSEXGKCCSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of PD-I/PD-L1 interaction (unknown origin)
Measurement: IC50 = 2.25 nM (pChEMBL 8.649999618530273)
Descriptors: MW 580.64, ALogP 5, HBA 8, HBD 3, PSA 130.27, QED 0.21
Compound (SMILES): COCCOc1cccc(-c2cccc3c2CC[C@@H]3Oc2nc(OC)c(CNCCO)cc2Cl)c1
InChIKey: LAAOOVJWJCPXMQ-VWLOTQADSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of PD-1/PD-L1 (unknown origin) protein-protein interaction incubated for 15 mins by TR-FRET assay
Measurement: IC50 = 94.5 nM (pChEMBL 7.03000020980835)
Descriptors: MW 499.01, ALogP 4.58, HBA 7, HBD 2, PSA 82.07, QED 0.35
Compound (SMILES): Cl.N[C@H]1CCN(c2c3c(nc4ccc(-c5ccnc(NC(=O)C6CC6)c5)cc24)-c2ccccc2CCC3)C1
InChIKey: FXFJEJCSJUOOGD-BQAIUKQQSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human full length CDK2/CyclinA2 by ADP-Glo kinase assay
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 489.62, ALogP 5.34, HBA 5, HBD 2, PSA 84.14, QED 0.4
Compound (SMILES): N[C@H](C[C@H]1CC(C(=O)O)=NN1c1ccc(CCCF)cc1)C(=O)O
InChIKey: ZWTILPSLFKCBIA-QWHCGFSZSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2A (PROTEIN COMPLEX), Homo sapiens
UniProt: Q05586
Assay: Binding affinity to GluN1/GluN2A receptor (unknown origin) assessed as inhibition constant
Measurement: Ki = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 337.35, ALogP 1.41, HBA 5, HBD 3, PSA 116.22, QED 0.66
Compound (SMILES): O=C(Nc1ccc(S(=O)(=O)Nc2ccccc2)cc1)c1ccc(C(F)(F)F)cc1C(F)(F)F
InChIKey: MSULVBNDVZZKMQ-UHFFFAOYSA-N
Target: GPR27-V2 (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q9NS67
Assay: Agonist activity at CLuc-tagged human GPR27-V2 expressed in HEK293 cells incubated for 10 mins by beta-arrestin 2 recruitment based firefly luciferase complementation assay
Measurement: EC50 = 549.54 nM (pChEMBL 6.260000228881836)
Descriptors: MW 488.41, ALogP 5.78, HBA 3, HBD 2, PSA 75.27, QED 0.45
Compound (SMILES): COc1cc(-c2cn(Cc3cn4cc(CNCC56CC(F)(C5)C6)ccc4n3)nn2)c2cncn2c1
InChIKey: KTHCGQRAINDGSY-UHFFFAOYSA-N
Target: METTL3/METTL14 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5'P-uacacucgaucuggacuaaagcugcuc-3' and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis
Measurement: IC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 472.53, ALogP 3.28, HBA 9, HBD 1, PSA 86.57, QED 0.37
Compound (SMILES): O=C(O)COc1cc(F)c2c(c1)CC(CNCCC1CN(c3ccc4c(n3)NC(=O)CO4)C(=O)O1)C2
InChIKey: QRLSRELXQXBCKO-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES6
Assay: Inhibition of Escherichia coli DNA gyrase incubated for 80 mins by Transcreener ADP2 FI assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 500.48, ALogP 1.73, HBA 8, HBD 3, PSA 139.32, QED 0.44
Compound (SMILES): CC(C)c1cc(N[C@H]2CC[C@H](N)CC2)n2nccc2n1
InChIKey: GKGYWAYUFTYFFF-HAQNSBGRSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of human CDK9/Cyclin T1 preincubated for 20 mins followed by 32P-ATP addition and measured after 2 hrs
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 273.38, ALogP 2.53, HBA 5, HBD 2, PSA 68.24, QED 0.9
Compound (SMILES): CC(C)(Oc1cccc(C2CCCN(C(=O)OCc3ccc(C(C)(C)C)cc3)C2)c1)C(=O)O
InChIKey: IFEYWWNVRDYJAA-UHFFFAOYSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: P35222
Assay: Inhibition of N-terminal His6-tagged full-length recombinant beta-catenin (1 to 781 residues) (unknown origin) expressed in Escherichia coli BL21 DE3/N-terminal FAM tagged BCL9 HD2(350 to 375 residues) (unknown origin) protein-protein interaction assessed as inhibition constant incubated for 3 hrs by competitive fluorescence polarization assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 453.58, ALogP 5.74, HBA 4, HBD 1, PSA 76.07, QED 0.6
Compound (SMILES): C[C@H]1CCCN1C(=O)c1ccc2cnc(NC3CCN(S(N)(=O)=O)CC3)nc2c1
InChIKey: WQXUQKYTKVVMDE-ZDUSSCGKSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Binding affinity to CDK2/Cyclin E1 (unknown origin) using Ulight-MBP as substrate assessed as inhibition constant preincubated for 30 mins followed by substrate addition measured after 90 mins in presence of ATP by TR-FRET assay
Measurement: Ki = 0.18 nM (pChEMBL 9.739999771118164)
Descriptors: MW 418.52, ALogP 1.33, HBA 6, HBD 2, PSA 121.52, QED 0.77
Compound (SMILES): COc1nc(O[C@H]2CCc3c(-c4ccc5c(c4)OCCO5)cccc32)c(Cl)cc1CN1CC[C@H](O)C1
InChIKey: QQOXJDVCJMNEDC-CYFREDJKSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of PD-1/PD-L1 (unknown origin) protein-protein interaction incubated for 15 mins by TR-FRET assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 509, ALogP 4.81, HBA 7, HBD 1, PSA 73.28, QED 0.51
Compound (SMILES): O=C1COc2ccc(N3CC(CNCC4Cc5cccc(Cl)c5C4)OC3=O)nc2N1
InChIKey: CPTVFJTVHOYDTL-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES6
Assay: Inhibition of Escherichia coli DNA gyrase ATPase activity incubated for 80 mins
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 428.88, ALogP 2.4, HBA 6, HBD 2, PSA 92.79, QED 0.76
Compound (SMILES): Cc1cc([C@H](NC(=O)c2cnccc2-c2ccc(C(F)(F)F)cc2)C(=O)N(C)C)cc(C(F)(F)F)c1
InChIKey: KPDNRBOZALCFHR-NRFANRHFSA-N
Target: NKGD2-MICA (PROTEIN COMPLEX), Homo sapiens
UniProt: P26718
Assay: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 509.45, ALogP 5.65, HBA 3, HBD 1, PSA 62.3, QED 0.45
Compound (SMILES): Cl.N[C@H]1CCN(c2c3c(nc4ccc(-c5ccnc(NC(=O)C6CC6)n5)cc24)-c2ccccc2CCC3)C1
InChIKey: AGVGOCHGKRMMQH-BOXHHOBZSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human full length CDK2/CyclinA2 by ADP-Glo kinase assay
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 490.61, ALogP 4.73, HBA 6, HBD 2, PSA 97.03, QED 0.43
Compound (SMILES): COc1c(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)C2(C#N)CC2)C(C)(C)C)ccc(-c2scnc2C)c1F
InChIKey: MGKVOYJDCPJZFX-HFJQGTKSSA-N
Target: Von Hippel-Lindau disease tumor suppressor/Elongin B/Elongin C (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15370
Assay: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay
Measurement: Kd = 305 nM (pChEMBL 6.519999980926514)
Descriptors: MW 571.68, ALogP 2.68, HBA 8, HBD 3, PSA 144.65, QED 0.44
Compound (SMILES): O=C(N[C@H](C(=O)N1C[C@@H]2[C@H](CO)[C@@H]2C1)c1cccc(C(F)(F)F)c1)c1ccccc1-c1ccc(C(F)(F)F)cc1
InChIKey: LLNURPOWMDHYAG-NDBXHCKUSA-N
Target: NKGD2-MICA (PROTEIN COMPLEX), Homo sapiens
UniProt: P26718
Assay: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 562.51, ALogP 5.56, HBA 3, HBD 2, PSA 69.64, QED 0.39
Compound (SMILES): COc1c(COc2ccc(CNCCNC(C)=O)c(OCc3cccc(C#N)c3)c2)cccc1-c1cccc(F)c1
InChIKey: ZEVWBYPHMAMCIO-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of PD-1/PD-L1 interaction (unknown origin) incubated for 1 hr by HTRF assay
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 553.63, ALogP 5.76, HBA 6, HBD 2, PSA 92.61, QED 0.2
Compound (SMILES): CN(C)C(=O)C(NS(=O)(=O)c1ccccc1-c1ccc(C(F)(F)F)cc1)c1cccc(C(F)(F)F)c1
InChIKey: OSNCTIGQXVWPDO-UHFFFAOYSA-N
Target: NKGD2-MICA (PROTEIN COMPLEX), Homo sapiens
UniProt: P26718
Assay: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 530.49, ALogP 5.5, HBA 3, HBD 1, PSA 66.48, QED 0.43
Compound (SMILES): Nc1ncnc2c1ccn2[C@@H]1C[C@H](c2ccc3cc(CN4CCC5(CCC5)C4)[nH]c3c2)[C@@H](O)[C@H]1O
InChIKey: FOQRTFBODRTNCT-BUZMGHMJSA-N
Target: METTL3/METTL14 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5'P-uacacucgaucuggacuaaagcugcuc-3' and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis
Measurement: IC50 = 6.22 nM (pChEMBL 8.210000038146973)
Descriptors: MW 472.59, ALogP 3.32, HBA 7, HBD 4, PSA 116.22, QED 0.36
Compound (SMILES): C=CC(=O)N1CCN(c2nc(OC[C@@H]3CCCN3C)nc3c2cc(-c2ccc4[nH]ncc4c2)n3C)C[C@@H]1CC#N
InChIKey: QWDPXZQJFRUHMP-VXKWHMMOSA-N
Target: SOS1-KRAS (PROTEIN COMPLEX), Homo sapiens
UniProt: Q07889
Assay: Inhibition of KRAS G12C mutant/SOS1 (unknown origin) interaction incubated for 2 hrs in presence of GTP by HTRF assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 539.64, ALogP 3.1, HBA 9, HBD 1, PSA 119.2, QED 0.36
Compound (SMILES): COCCNCc1cc(Cl)c(OCc2cccc(-c3cccc4c(Oc5cc(OCc6cccc(C#N)c6)c(CNCCOC)cc5Cl)ncnc34)c2C)cc1OCc1cccc(C#N)c1
InChIKey: JHPHUDXDDNAINK-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of PD-1/PD-L1 interaction (unknown origin) incubated for 60 min by HTRF assay
Measurement: IC50 = 100.55 nM (pChEMBL 7)
Descriptors: MW 923.9, ALogP 10.66, HBA 12, HBD 2, PSA 152.8, QED 0.06
Compound (SMILES): COc1c(COc2ccc(CNCCO)c(OCc3cccc(C#N)c3)c2)cccc1-c1ccccc1
InChIKey: FGZAIEKCMDHOBE-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of PD-1/PD-L1 interaction (unknown origin) incubated for 1 hr by HTRF assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 494.59, ALogP 5.47, HBA 6, HBD 2, PSA 83.74, QED 0.25
Compound (SMILES): Cc1cc(-c2scnc2C)ccc1CNC(=O)[C@@H]1C[C@@H](O)CN1C(=O)[C@@H](NC(=O)C1(F)CC1)C(C)(C)C
InChIKey: UTAPHNUQQSHJDU-RZUBCFFCSA-N
Target: Von Hippel-Lindau disease tumor suppressor/Elongin B/Elongin C (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15370
Assay: Binding affinity to N-terminal His6-tagged VHL (54 to 213 residues)/Elongin B/Elogin C (unknown origin) using (FAM)-labeled HIF-1alpha peptide as substrate assessed as dissociation constant by fluorescence polarization assay
Measurement: Kd = 112 nM (pChEMBL 6.949999809265137)
Descriptors: MW 530.67, ALogP 3.04, HBA 6, HBD 3, PSA 111.63, QED 0.51
Compound (SMILES): O=C(NCc1cccc(C(F)(F)F)c1)c1ccccc1-c1ccc(C(F)(F)F)cc1
InChIKey: VHZQPWVWPKWNNK-UHFFFAOYSA-N
Target: NKGD2-MICA (PROTEIN COMPLEX), Homo sapiens
UniProt: P26718
Assay: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 423.36, ALogP 6.32, HBA 1, HBD 1, PSA 29.1, QED 0.49
Compound (SMILES): CN(C)C(=O)[C@@H](NC(=O)c1cc(-c2nnnn2C)ccc1-c1ccc(C(F)(F)F)cc1)c1cccc(C(F)(F)F)c1
InChIKey: KAHIPVOFKWZPRL-QFIPXVFZSA-N
Target: NKGD2-MICA (PROTEIN COMPLEX), Homo sapiens
UniProt: P26718
Assay: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 576.5, ALogP 5.14, HBA 6, HBD 1, PSA 93.01, QED 0.32
Compound (SMILES): CN(C)C(=O)[C@@H](NC(=O)c1cnccc1-c1ccc(C(F)(F)F)cc1)c1ccc(Cl)c(Cl)c1
InChIKey: HJIASDAFCRTZFX-FQEVSTJZSA-N
Target: NKGD2-MICA (PROTEIN COMPLEX), Homo sapiens
UniProt: P26718
Assay: Inhibition of NKG2D (unknown origin)/MICA (unknown origin) protein-protein interaction by cell-based TR-FRET assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 496.32, ALogP 5.63, HBA 3, HBD 1, PSA 62.3, QED 0.5
Compound (SMILES): Cc1n[nH]c2ccc(-c3nnc(O)n3Cc3ccc(Cl)cc3)cc12
InChIKey: HMCHMMXFZPJORT-UHFFFAOYSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P49336
Assay: Inhibition of His tagged human recombinant CDK8/Cyclin C expressed in baculovirus expression system incubated for 15 mins by FRET-based LanthaScreen binding competition assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 339.79, ALogP 3.54, HBA 5, HBD 2, PSA 79.62, QED 0.6
Compound (SMILES): COc1cc(OCc2cccc(-c3ccccc3)c2C)cc(OC)c1CNCc1cnnn1[C@H]1OC[C@@H](O)[C@H](O)[C@@H]1O
InChIKey: YFAUARCACAJECW-DEGSFCBCSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of PD-1/PD-L1 (unknown origin) interaction incubated for 15 mins by HTRF assay
Measurement: IC50 = 168.9 nM (pChEMBL 6.769999980926514)
Descriptors: MW 576.65, ALogP 2.75, HBA 11, HBD 4, PSA 140.35, QED 0.21
Compound (SMILES): Cc1ccc(S(=O)(=O)N2CCN(C(=O)CCl)C2)cc1
InChIKey: KWRBOINXMJEMAS-UHFFFAOYSA-N
Target: YAP1-TEAD4 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15561
Assay: Inhibition of GST-tagged TEAD4 (217 to 434 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells/FAM-labelled YAP1 (60 to 99 residues)(unknown origin) protein-protein interaction preincubated for 24 hrs at 4 degree C with TEAD4 followed by fluorescent labelled YAP1 addition by fluorescence polarization assay
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 302.78, ALogP 1.02, HBA 3, HBD 0, PSA 57.69, QED 0.78
Compound (SMILES): CS(=O)(=O)NCCOc1cc(C#N)c2c(c1)CC(CNCCC1CN(c3ccc4c(n3)NC(=O)CO4)C(=O)O1)C2
InChIKey: REMFYECIOFGXBB-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES6
Assay: Inhibition of Escherichia coli DNA gyrase incubated for 80 mins by Transcreener ADP2 FI assay
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 570.63, ALogP 0.93, HBA 10, HBD 3, PSA 171.98, QED 0.33