lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CNS(=O)(=O)N1CCC(Nc2ncc3ccc(=O)n([C@@H]4C[C@@H](O)CC[C@H]4F)c3n2)CC1
InChIKey: COWPKYBSZGEQGW-ARFHVFGLSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: CDK2/Cyclin E1 Mobility Shift Assay: The purpose of the CDK2/Cyclin E1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) of small molecule inhibitors by using a fluorescence-based microfluidic mobility shift assay. CDK2/Cyclin E1 catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide FL-Peptide-18 (5-FAM-QSPKKG-CONH2) (SEQ ID NO:1). (CPC Scientific, Sunnyvale, Calif.). 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. Wild-type full length CDK2/wild-type full length Cyclin E1 enzyme complex was produced in-house (baculoviral expression, LJIC-2080/LJIC-2103) and phosphorylated by CDK7/Cyclin H1/Mat1 enzyme complex with CDK2:CDK7 ratio of 50:1 (concentration mg/mL) in the presence of 10 mM MgCl2 and 5 mM ATP at room temperature for one hour. Typical reaction solutions (50 μL final reaction volume) contained 2% DMSO (± inhibitor), 4 mM MgCl2, 1 mM DTT, 150 μM ATP (ATP Km=67.4 μM), 0.005% Tween-20, 3 μM FL-Peptide-18, and 0.36 nM (catalytically competent active site) phosphorylated wild-type full length CDK2/Cyclin E1 enzyme complex in 25 mM HEPES buffer at pH 7.15. The assay was initiated with the addition of ATP, following a fifteen minutes pre-incubation of enzyme and inhibitor at room temperature in the reaction mixture. The reaction was stopped after 45 minutes at room temperature by the addition of 50 μL of 80 mM EDTA, pH 7.5. The Ki value was determined from the fit of the data to the Morrison tight-binding competitive inhibition equation with the enzyme concentration as a variable.
Measurement: Ki = 7.46 nM (pChEMBL 8.130000114440918)
Descriptors: MW 454.53, ALogP 0.56, HBA 8, HBD 3, PSA 129.45, QED 0.6
Compound (SMILES): Cc1cnc(NCc2cn(-c3ccc(F)c(C(F)F)c3)nn2)nc1
InChIKey: FILPSSROSVJMRN-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: NMDA receptor FLIPR assay: 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 149 mM NaCl, 4 mM KCl, 2 mM CaCl2, and 1.5 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 (149 mM NaCl (standard assay) or 150 mM (HTS assay), 4 mM KCl (standard assay) or 3 mM (HTS assay), 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 EC80 (standard assay) or EC40 (HTS assay) is used to maximize the assay's signal window or the ability to detect NMDA receptor antagonists and negative allosteric modulators, respectively. 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 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 334.3, ALogP 3.05, HBA 6, HBD 1, PSA 68.52, QED 0.78
Compound (SMILES): COc1cc(CC(=O)Nc2cc([C@@H]3CC[C@H](OC(=O)N4C[C@@](C)(O)[C@@H]4C)C3)[nH]n2)ccn1
InChIKey: XXHPNVKTJQFFNL-CFZSEITHSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Biochemical Assay: The purpose of CDK2/Cyclin E1 assay is to evaluate the inhibition (% inhibition, Kiapp and Ki values) of small molecule inhibitors by using a fluorescence-based microfluidic mobility shift assay. CDK2/Cyclin E1 full length catalyzes the production of ADP from ATP that accompanies the phosphoryl transfer to the substrate peptide FL-Peptide-18 (5-FAM-QSPKKG-CONH2, CPC Scientific, Sunnyvale, Calif.) (SEQ ID NO:1). 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. Wild-type CDK2/wild-type full length Cyclin E1 enzyme complex was produced in-house (baculoviral expression, LJIC-2080/LJIC-2103) and phosphorylated by CDK7/Cyclin H1/Matl enzyme complex with CDK2:CDK7 ratio of 50:1 (concentration mg/mL) in the presence of 10 mM MgCl2 and 5 mM ATP at room temperature for one hour. Typical reaction solutions (50 μL final reaction volume) contained 2% DMSO (±inhibitor), 4 mM MgCl2, 1 mM DTT, 150 μM ATP (ATP Km=67.4 μM), 0.005% Tween-20, 3 μM FL-Peptide-18, and 0.36 nM (catalytically competent active site) phosphorylated wild-type full length CDK2/Cyclin E1 enzyme complex in 25 mM HEPES buffer at pH 7.15. The assay was initiated with the addition of ATP, following a fifteen minutes pre-incubation of enzyme and inhibitor at room temperature in the reaction mixture. The reaction was stopped after 45 minutes at room temperature by the addition of 50 μL of 80 mM EDTA.
Measurement: Ki = 4.18 nM (pChEMBL 8.380000114440918)
Descriptors: MW 443.5, ALogP 2.22, HBA 7, HBD 3, PSA 129.67, QED 0.62
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cc(F)c4nn(C)c(C(C)(O)C(F)(F)F)c4c3)c(C)cn2)C1
InChIKey: CEERPSVTLJOQDZ-OCWAHVNLSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: CDK2/CyclinA2 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). CDK2/Cyclin A2 catalyzed phosphorylation of peptide in the presence and absence of compounds was measured and used in IC50 determination. Recombinant protein complex CDK2/Cyclin A2, 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 CDK2/CyclinA2 (1 nM final), ULight-4E-BP1 (50 nM final, Perkinelmer, TRF0128-D), and ATP (1 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 = 133 nM (pChEMBL 6.880000114440918)
Descriptors: MW 535.54, ALogP 4.49, HBA 6, HBD 3, PSA 109.14, QED 0.42
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCS(=O)(=O)CC3)cc12
InChIKey: IUYOYZMDPKJHIE-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 372.42, ALogP 3.58, HBA 4, HBD 1, PSA 72.05, QED 0.76
Compound (SMILES): O=C(NC(CCO[C@H]1C[C@H](CCc2ccc3c(n2)NCCC3)C1)C(=O)O)c1ccccn1
InChIKey: DXSAJEJULNERIL-BXPIPXIPSA-N
Target: Integrin alpha-V/beta-6 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18564
Assay: Binding Assay: The biochemical potency of compounds was determined using a proximity-based assay (ALPHASCREEN®, Perkin Elmer, Waltham, Mass.) as described previously (Ullman E F et al., Luminescent oxygen channeling immunoassay: Measurement of particle binding kinetics by chemiluminescence. Proc. Natl. Acad. Sci. USA, Vol. 91, pp. 5426-5430, June 1994). To gauge the potency of inhibitors of binding to human integrin αvβ6, inhibitor compounds and integrin were incubated together with TGF-b1 LAP and biotinylated anti-LAP antibody plus acceptor and donor beads, following the manufacture's recommendations. The donor beads were coated with streptavidin. The acceptor beads had a nitrilotriacetic acid Ni chelator, for binding to a 6×His Tag on human integrin αvβ6. All incubations occurred at room temperatures in 50 mM Tris-HCl, pH 7.5, 0.1% BSA supplemented with 1 mM each CaCl2 and MgCl2.The order of reagent addition was as follows:1. Alpha-v-beta-6 integrin, test inhibitor compound, LAP, biotinylated anti-LAP antibody and acceptor beads were all added together.2. After 2 hours, donor beads were added. After another 30 minute incubation, samples were then read.Integrin binding was evaluated by exciting donor beads at 680 nm, and measuring the fluorescent signal produced, between 520-620 nm, using a Biotek Instruments (Winooski, Vt., USA) SynergyNeo2 multimode plate reader.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 438.53, ALogP 2.84, HBA 6, HBD 3, PSA 113.44, QED 0.52
Compound (SMILES): CCOC(=O)NS(=O)(=O)N1C2C=C(c3cc4c(-c5cc(F)ccc5OC)ccnc4[nH]3)CC1CC2
InChIKey: LCQGHWPYBIVMFU-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 500.55, ALogP 3.99, HBA 6, HBD 2, PSA 113.62, QED 0.53
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCN(CC(=O)N4CCC[C@H]4C(=O)O)CC3)cc12
InChIKey: OOJDWZCGWHODGV-QFIPXVFZSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 478.52, ALogP 3.54, HBA 5, HBD 2, PSA 98.76, QED 0.56
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3=CCN(S(C)(=O)=O)[C@H](C)C3)cc12
InChIKey: GWWZXSURAHYRGC-CYBMUJFWSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 415.49, ALogP 3.81, HBA 4, HBD 1, PSA 75.29, QED 0.7
Compound (SMILES): COc1ccc(F)cc1-c1c(F)cnc2[nH]c(C3=CCN(S(C)(=O)=O)CC3)cc12
InChIKey: WNNCPXCYBZTNCH-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 419.45, ALogP 3.57, HBA 4, HBD 1, PSA 75.29, QED 0.7
Compound (SMILES): COc1ccc(F)cc1-c1ccnc2[nH]c(C3CCNCC3)c(Br)c12
InChIKey: MSIDHBBXOAWUER-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: LANCE ULight TR-FRET Kinase Assay: CDK9 enzyme activities were measured using LANCE ULight TR-FRET kinase assay reagents (PerkinElmer, Waltham, Mass.). Compounds were directly added in 100% DMSO to white low volume assay plates (Perkin Elmer Proxiplate 6008289) using a Labcyte Echo acoustic dispenser. Assay reagents in serine/threonine kinase assay buffer containing 20 mM HEPES, 10 mM MgCl2, 100 mM Na3VO4, and 0.0075% Triton X-100. were added for final reaction mixture concentrations of 1000 μM ATP, 100 nM U-light MBP peptide (Perkin Elmer TRF0109M) and reaction initiated with 4 nM CDK9/Cyclin T1 (Carna Biosciences 04-110). The kinase reaction was carried out for 30 minutes before addition of stopping buffer to a final of 20 mM EDTA and 0.5 nM of LANCE Ultra Europium anti-phospho-MBP antibody (PerkinElmer TRF0201M) in LANCE detection buffer (PerkinElmer CR97-100). The reaction was equilibrated for 1 hour and the signal read in the Perkin Elmer Envision in TR-FRET mode (excitation at 320 nm and emission at 615/665 nm).
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 404.28, ALogP 4.61, HBA 3, HBD 2, PSA 49.94, QED 0.67
Compound (SMILES): C=CC(=O)N1CCC(C(=O)Nc2cccc(CNc3nc(OC4CCN(C)CC4)nc4c(C(C)C)cnn34)c2)CC1
InChIKey: RZLRMJBYKRNXCB-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Biochemical Assay for CDK7: The ability of compounds to inhibit CDK7 kinase activity was tested in a TR-FRET assay using 5 nM of CDK7/CycH/MNAT1 obtained from Invitrogen, USA. Test compounds were pre-incubated with the kinase at room temperature for 60 min. After incubation, substrate mix [100 nM Ultra-light MBP (Perkin Elmer, USA) and 1 mM ATP (Sigma)] was added. The above reaction was stopped by the addition of 40 mM EDTA after 60 minutes of kinase reaction. 1 nM Eu-labelled antiphospho-MBP antibody [Perkin Elmer, USA] was added, mixed well and the fluorescence emission at 615 nm and 665 nm [excitation at 340 nm] was measured. The final DMSO concentration in the assay was 1%. For IC50 determination, appropriate concentrations were made by ⅓rd serial dilutions of 10 mM DMSO stock solution of test compound. All the fluorescence measurements were made in a Victor 3 Multilabel Counter [Perkin Elmer, USA]. The IC50 was determined by fitting the dose response data to sigmoidal curve fitting equation using GraphPad Prism software V5. To identify compounds that inhibit CDK7 irreversibly, time depended inhibition studies were carried by pre-incubating compound with the enzyme at three time points (20, 60 and 180 min) and carrying out assay as described above.
Measurement: IC50 < 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 560.7, ALogP 3.7, HBA 9, HBD 2, PSA 116.99, QED 0.38
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)Nc2cccc(Nc3n[nH]c4ccccc34)c2)cc1
InChIKey: RTFSYHAIVUXTEI-IZZDOVSWSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Biochemical Assay: The ability of compounds to inhibit CDK7 kinase activity was tested in a TR-FRET assay using 5 nM of CDK7/CycH/MNAT1 obtained from Invitrogen, USA. Test compounds were pre-incubated with the kinase at room temperature for 60 min. After the incubation, substrate mix [100 nM Ultra-light MBP (Perkin Elmer, USA) and 1 mM ATP (Sigma)] was added. The above reaction was stopped by the addition of 40 mM EDTA after 60 minutes of kinase reaction. 1 nM Eu-labelled antiphospho-MBP antibody [Perkin Elmer, USA] was added, mixed well and the fluorescence emission at 615 nm and 665 nm [excitation at 340 nm] was measured. The final DMSO concentration in the assay was 1%. For IC50 determination, appropriate concentrations were made by ⅓rd serial dilutions of 10 mM DMSO stock solution of test compound. All the fluorescence measurements were made in a Victor 3 Multilabel Counter [Perkin Elmer, USA]. The IC50 was determined by fitting the dose response data to sigmoidal curve fitting equation using GraphPad Prism software V5. To identify compounds that inhibit CDK7 irreversibly, time depended inhibition studies were carried by pre-incubating compound with the enzyme at three time points (20, 60 and 180 min) and carrying out assay as described above.
Measurement: IC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 454.53, ALogP 4.62, HBA 5, HBD 4, PSA 102.15, QED 0.29
Compound (SMILES): CC(C(=O)Nc1cc(C2CC2)[nH]n1)c1cccc(-c2ccc(NC(=O)/C=C/CN(C)C)c(F)n2)c1
InChIKey: YLAFDLZUXMDTQR-VMPITWQZSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Biochemical Assay: The ability of compounds to inhibit CDK7 kinase activity was tested in a TR-FRET assay using 5 nM of CDK7/CycH/MNAT1 obtained from Invitrogen, USA. Test compounds were pre-incubated with the kinase at room temperature for 60 min. After the incubation, substrate mix [100 nM Ultra-light MBP (Perkin Elmer, USA) and 1 mM ATP (Sigma)] was added. The above reaction was stopped by the addition of 40 mM EDTA after 60 minutes of kinase reaction. 1 nM Eu-labelled antiphospho-MBP antibody [Perkin Elmer, USA] was added, mixed well and the fluorescence emission at 615 nm and 665 nm [excitation at 340 nm] was measured. The final DMSO concentration in the assay was 1%. For IC50 determination, appropriate concentrations were made by ⅓rd serial dilutions of 10 mM DMSO stock solution of test compound. All the fluorescence measurements were made in a Victor 3 Multilabel Counter [Perkin Elmer, USA]. The IC50 was determined by fitting the dose response data to sigmoidal curve fitting equation using GraphPad Prism software V5. To identify compounds that inhibit CDK7 irreversibly, time depended inhibition studies were carried by pre-incubating compound with the enzyme at three time points (20, 60 and 180 min) and carrying out assay as described above.
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 476.56, ALogP 4.29, HBA 5, HBD 3, PSA 103.01, QED 0.32
Compound (SMILES): C=CC(=O)N1CCC(C(=O)Nc2cccc(CNc3nc(OC4CCN(C)CC4)nc4c(C(C)C)cnn34)c2)CC1
InChIKey: RZLRMJBYKRNXCB-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Biochemical Assay for CDK7: The ability of compounds to inhibit CDK7 kinase activity was tested in a TR-FRET assay using 5 nM of CDK7/CycH/MNAT1 obtained from Invitrogen, USA. Test compounds were pre-incubated with the kinase at room temperature for 60 min. After incubation, substrate mix [100 nM Ultra-light MBP (Perkin Elmer, USA) and 1 mM ATP (Sigma)] was added. The above reaction was stopped by the addition of 40 mM EDTA after 60 minutes of kinase reaction. 1 nM Eu-labelled antiphospho-MBP antibody [Perkin Elmer, USA] was added, mixed well and the fluorescence emission at 615 nm and 665 nm [excitation at 340 nm] was measured. The final DMSO concentration in the assay was 1%. For IC50 determination, appropriate concentrations were made by ⅓rd serial dilutions of 10 mM DMSO stock solution of test compound. All the fluorescence measurements were made in a Victor 3 Multilabel Counter [Perkin Elmer, USA]. The IC50 was determined by fitting the dose response data to sigmoidal curve fitting equation using GraphPad Prism software V5. To identify compounds that inhibit CDK7 irreversibly, time depended inhibition studies were carried by pre-incubating compound with the enzyme at three time points (20, 60 and 180 min) and carrying out assay as described above.
Measurement: IC50 < 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 560.7, ALogP 3.7, HBA 9, HBD 2, PSA 116.99, QED 0.38
Compound (SMILES): O[C@@H]1[C@H](O)CS[C@H]1Cn1cnc2c(NCc3cccc(Cl)c3)nc(I)nc21
InChIKey: JKWBJAPOWMKHMQ-MBNYWOFBSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Binding affinity to PPARgamma (unknown origin) assessed as inhibition constant by TR-FRET based LanthaScreen competitive binding assay
Measurement: Ki = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 517.78, ALogP 2.53, HBA 8, HBD 3, PSA 96.09, QED 0.35
Compound (SMILES): Fc1cc2c(cc1C(F)(F)F)[I+]c1ccccc1-2
InChIKey: GMCBSUPVCJRXHP-UHFFFAOYSA-N
Target: G-protein coupled receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P46089
Assay: Agonist activity at human GPR3 expressed in HEK293 cells assessed as increase in cAMP accumulation incubated for 30 mins by HTRF assay
Measurement: EC50 = 816 nM (pChEMBL 6.090000152587891)
Descriptors: MW 365.09, ALogP 0.95, HBA 0, HBD 0, PSA 0, QED 0.41
Compound (SMILES): O=c1c2[nH]cnc2ncn1Cc1nc(CCc2ccc(Cl)cc2)no1
InChIKey: WKEGRPVOXGQXBX-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: Antagonist activity at human wildtype TRPA1 channel expressed in CHO-K1 cells tagged with GCaMP6 by measuring calcium flux measured after 24 hrs by FLIPR tetra analysis
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 356.77, ALogP 1.99, HBA 7, HBD 1, PSA 102.49, QED 0.59
Compound (SMILES): CN(C)S(=O)(=O)Nc1cccc(-c2cnn(-c3ccc(C(F)(F)F)cc3)c2)c1
InChIKey: LBWLRTSCQVOYBQ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin)
Measurement: IC50 = 13600 nM (pChEMBL 4.869999885559082)
Descriptors: MW 410.42, ALogP 3.78, HBA 4, HBD 1, PSA 67.23, QED 0.7
Compound (SMILES): COc1ccc(S(=O)(=O)N(CC(C)C)C[C@@H](O)[C@H](Cc2ccccc2)NC(=O)Cc2ccc(OC)c(O)c2)cc1
InChIKey: GBCFCOHYZDIYSL-XTEPFMGCSA-N
Target: Human immunodeficiency virus type 1 protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72874
Assay: Inhibition of HIV-1 protease by fluorescence resonance energy transfer analysis
Measurement: IC50 = 3.97 nM (pChEMBL 8.399999618530273)
Descriptors: MW 570.71, ALogP 3.39, HBA 7, HBD 3, PSA 125.4, QED 0.27
Compound (SMILES): CCOc1ccn(-c2ccc(F)cc2)c(=O)c1C(=O)Nc1ccc(Oc2ccnc3cc(-c4ccc(CN5CCN(C)CC5)cn4)sc23)c(F)c1
InChIKey: KGRZLPCJGDFXPZ-UHFFFAOYSA-N
Target: Macrophage-stimulating protein receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q04912
Assay: Inhibition of N-terminal GST-tagged human recombinant RON (979 to 1400(end) residues) expressed in Sf21 cells incubated for 20 mins followed by ATP addition measured after 60 mins by TR-FRET based LanthaScreen kinase assay
Measurement: IC50 = 0.26 nM (pChEMBL 9.59000015258789)
Descriptors: MW 708.79, ALogP 6.98, HBA 10, HBD 1, PSA 101.82, QED 0.16
Compound (SMILES): CC(C)(C)C(=O)CSc1nccc(-c2ccccc2)n1
InChIKey: DRXDOWYEEFFVID-UHFFFAOYSA-N
Target: Dual specificity protein phosphatase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6W6
Assay: Inhibition of MKP5 catalytic domain (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as p38alpha MAPK phosphopeptide dephosphorylation using phosphopeptide as substrate incubated for 15 mins followed by substrate addition by malachite green dye based analysis
Measurement: IC50 = 27000 nM (pChEMBL 4.570000171661377)
Descriptors: MW 286.4, ALogP 3.85, HBA 4, HBD 0, PSA 42.85, QED 0.63
Compound (SMILES): C[C@H](Oc1cc(NC(=O)N2CCC(F)(F)C2)c(F)cc1C(=O)Nc1c(F)cccc1Cl)C(F)(F)F
InChIKey: AQGDJJBWAIAJJW-JTQLQIEISA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of human DHODH in MOLM-13 AML cells
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 527.82, ALogP 6.07, HBA 3, HBD 2, PSA 70.67, QED 0.46
Compound (SMILES): Cc1cc(-n2c(Cc3ccccc3)nc3cc(O)c(O)c(O)c3c2=O)ccc1F
InChIKey: APMHTYDRRIVKNO-UHFFFAOYSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 Main protease expressed in Escherichia coli BL21 (DE3) using fluorogenic peptide Dabcyl-KLSAVLQSGFRKM-Edans-NH2 as substrate incubated for 30 mins by fluorescence resonance energy transfer (FRET)-based enzymatic assay
Measurement: IC50 = 502 nM (pChEMBL 6.300000190734863)
Descriptors: MW 392.39, ALogP 3.54, HBA 6, HBD 3, PSA 95.58, QED 0.46
Compound (SMILES): Cc1nc2nc(C)c(CCNC(=O)c3cnc(-c4ccc(CN5CCOCC5)cc4)cn3)c(C)n2n1
InChIKey: OBAKHRPSDRUWQU-UHFFFAOYSA-N
Target: Monocarboxylate transporter 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15427
Assay: Inhibition of MCT4 in human SK-BR-3 cells assessed as inhibition of lactate efflux incubated for 4 hrs by automated microplate reader analysis
Measurement: IC50 = 6.8 nM (pChEMBL 8.170000076293945)
Descriptors: MW 486.58, ALogP 2.31, HBA 9, HBD 1, PSA 110.43, QED 0.42
Compound (SMILES): CNCCCCCn1c(-c2ncc(-c3ccc4ccccc4c3)n2CC2CCCCC2)cnc1I
InChIKey: JJTSSDXAZRZBLA-UHFFFAOYSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P04035
Assay: Inhibition of HMG CoA reductase (unknown origin) measured for 10 mins in presence of NADPH by microplate reader analysis
Measurement: IC50 = 36210 nM (pChEMBL 4.440000057220459)
Descriptors: MW 581.55, ALogP 7.14, HBA 5, HBD 1, PSA 47.67, QED 0.16
Compound (SMILES): CN(Cc1ccccc1)c1ncc(C(=O)Nc2ccccc2)c(N)n1
InChIKey: IYPAYKICVOQOPR-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of pIRS-1 peptide activated human wild type SHP2 FL (Met1 to Leu525 residues) using DiFMUP as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins by microplate reader method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 333.4, ALogP 2.95, HBA 5, HBD 2, PSA 84.14, QED 0.75
Compound (SMILES): N[C@@H](COP(=O)(O)OCCCOC(=O)CCc1ccccc1Oc1ccc(C23C[C@H]4C[C@@H](C2)C[C@@H](C3)C4)cc1)C(=O)O
InChIKey: GVWBQEGKFMPZJZ-IEQKDCSDSA-N
Target: Putative P2Y purinoceptor 10 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BFU7
Assay: Agonist activity at mouse LPS2/P2Y10 transfected in HEK293-A cells co-transfected with AP-TGFalpha assessed as AP-TGFalpha release by TGFalpha shedding assay
Measurement: EC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 601.63, ALogP 5.36, HBA 8, HBD 3, PSA 154.61, QED 0.14
Compound (SMILES): CCOC(=O)c1cnc(Nc2ccccc2Br)nc1NCCCNC(=S)NCCC(=O)O
InChIKey: VXZREVVTALPCLJ-UHFFFAOYSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys (Su)-AMC as fluorogenic substrate in presence of NAD+
Measurement: IC50 = 4060 nM (pChEMBL 5.389999866485596)
Descriptors: MW 525.43, ALogP 2.9, HBA 8, HBD 5, PSA 137.5, QED 0.16
Compound (SMILES): Cc1cccc2c(-c3ncc4c(n3)N3CCOC[C@@]3(C)C(=O)N4[C@H]3CC[C@H](O)CC3)c[nH]c12
InChIKey: ZSIRAWAQTMHYAU-TZPNTHKFSA-N
Target: mTORC2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BPZ7
Assay: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 447.54, ALogP 3.18, HBA 6, HBD 2, PSA 94.58, QED 0.63
Compound (SMILES): C[C@H](NC(=O)c1c(Nc2cccc([N+](=O)[O-])c2)c2ccccc2n1C)c1ccc(C(=O)O)cc1
InChIKey: QFBJMMNLGZGQHU-HNNXBMFYSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Antagonist activity at human EP4 receptor overexpressed in HEK293 cells assessed as inhibition of PGE2-induced cAMP formation preincubated for 15 mins followed by PGE addition and measured after 30 mins by Eu-cAMP tracer based assay
Measurement: IC50 = 57.3 nM (pChEMBL 7.239999771118164)
Descriptors: MW 458.47, ALogP 5.02, HBA 6, HBD 3, PSA 126.5, QED 0.26
Compound (SMILES): COc1cccc2c1OCC(C(=O)Nc1ccc3c(c1)CN(C1CCC(=O)NC1=O)C3=O)=C2
InChIKey: ZFAKJMUJUNDGEI-UHFFFAOYSA-N
Target: Cereblon/Casein kinase I alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P48729
Assay: Protac activity at CRBN/CK1alpha (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 447.45, ALogP 1.87, HBA 6, HBD 2, PSA 114.04, QED 0.69
Compound (SMILES): COc1ccc(C(=O)N2C(C)CN(C(=O)/C=C/c3ccc(Br)cc3)CC2C)cn1
InChIKey: BBYFIBZOKYHOIU-IZZDOVSWSA-N
Target: G-protein coupled receptor 183 (SINGLE PROTEIN), Homo sapiens
UniProt: P32249
Assay: Antagonist activity at human GPR183 expressed in CHO-K1 cells co-expressing Gqi5 assessed as inhibition of 7alpha,25-OHC induced calcium mobilization incubated for 30 mins by FLIPR Calcium 6 dye based assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 458.36, ALogP 3.63, HBA 4, HBD 0, PSA 62.74, QED 0.66
Compound (SMILES): COC(=O)c1ccc(/C=C2/C(=O)N(c3nc(-c4ccccc4OC)cs3)N=C2C)cc1
InChIKey: IVUZUTWGQUCUAL-LDADJPATSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human SIRT5 by fluorescence based analysis
Measurement: IC50 = 20580 nM (pChEMBL 4.690000057220459)
Descriptors: MW 433.49, ALogP 4.41, HBA 7, HBD 0, PSA 81.09, QED 0.44
Compound (SMILES): C=CC(=O)N1CCC(c2cc3c(Oc4ccc(NC(=O)NC5CC5)c(Cl)c4)ccnc3cc2OC)C(C)C1
InChIKey: MKSNIYIBUJCRQX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) incubated for 10 mins followed by substrate addition measured after 60 mins by ADP-Glo luminescence assay
Measurement: IC50 = 5.73 nM (pChEMBL 8.239999771118164)
Descriptors: MW 535.04, ALogP 6.11, HBA 5, HBD 2, PSA 92.79, QED 0.36
Compound (SMILES): O=C(Nc1c2c(nn1-c1ccc(Br)cc1)CSC2)c1cc(Cl)cc(Cl)c1
InChIKey: YRJDZTVMROWBPE-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of human ATX using LPC as substrate preincubated with compound for 15 mins followed by substrate addition measured after 30 mins by Amplex Red reagent based fluorescence analysis
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 469.19, ALogP 5.94, HBA 4, HBD 1, PSA 46.92, QED 0.52
Compound (SMILES): CN1CCN(CCc2ccc3nc4n(c(=O)c3c2)C2C=CC(F)=CC2C4=O)CC1
InChIKey: XBRGLEAUIBFXER-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of TDO (unknown origin) expressed in HEK293 cells
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 394.45, ALogP 1.96, HBA 6, HBD 0, PSA 58.44, QED 0.8
Compound (SMILES): CN(C)CCc1cc(F)c(F)c(CCc2cccc(N)n2)c1.Cl.Cl
InChIKey: IFMNJBDGKZTQSU-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29476
Assay: Inhibition of rat nNOS expressed in Escherichia coli using human oxyhemoglobin by hemoglobin (Hb) NO capture assay
Measurement: Ki = 1108 nM (pChEMBL 5.960000038146973)
Descriptors: MW 305.37, ALogP 2.83, HBA 3, HBD 1, PSA 42.15, QED 0.89
Compound (SMILES): O=C(O)CCNC(=S)NCCCNc1nc(Nc2ccccc2Cl)ncc1C(=O)N1CCCC(c2ccccc2)C1
InChIKey: ZSVNRUMSDRBCMI-UHFFFAOYSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys (Su)-AMC as fluorogenic substrate in presence of NAD+
Measurement: IC50 = 3660 nM (pChEMBL 5.440000057220459)
Descriptors: MW 596.16, ALogP 4.63, HBA 7, HBD 5, PSA 131.51, QED 0.15
Compound (SMILES): CN(C)CCOC(=O)Nc1ccc(-c2ccc3ncn(-c4cccc(NS(C)(=O)=O)c4)c3c2)cc1
InChIKey: LZOVBRZOLREDTR-UHFFFAOYSA-N
Target: Serine-protein kinase ATM (SINGLE PROTEIN), Homo sapiens
UniProt: Q13315
Assay: Inhibition of human ATM kinase using p53 as substrate by FRET assay
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 493.59, ALogP 4.17, HBA 7, HBD 2, PSA 105.56, QED 0.38
Compound (SMILES): CC(OC(C)(C)C)[C@H](NC(=O)OC(C)(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C=O)C[C@@H]1CCNC1=O
InChIKey: BOUXGXBQKDLEFW-WNBKYALVSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 3CL protease expressed in Escherichia coli BL21(DE3) cells using DABCYL-KTSAVLQSGFRKM-EDANS as substrate preincubated for 30 mins followed by substrate addition and measured after 15 mins by FRET assay
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 510.63, ALogP 1.28, HBA 7, HBD 3, PSA 143.14, QED 0.4
Compound (SMILES): Cc1cc(-c2ccc(S(N)(=O)=O)s2)cnc1-c1cccc2ccccc12
InChIKey: WUVPYPNAYVLIAX-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA XII (30 to 291 residues) expressed in escherichia coli BL21 assessed as inhibition constant preincubated for 15 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 212.5 nM (pChEMBL 6.670000076293945)
Descriptors: MW 380.49, ALogP 4.59, HBA 4, HBD 1, PSA 73.05, QED 0.57
Compound (SMILES): CCCN1CCN(C(=O)c2cc(Cn3c(=O)[nH]c(=O)c4ccccc43)ccc2F)CC1=O
InChIKey: JJDFDZDTXGPNIC-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of human recombinant PARP1 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay
Measurement: IC50 = 11.81 nM (pChEMBL 7.929999828338623)
Descriptors: MW 438.46, ALogP 1.57, HBA 5, HBD 1, PSA 95.48, QED 0.65
Compound (SMILES): O=C(NC1(c2ccc(Cl)cc2)COC1)c1ccc(CN2CCCC2=O)cc1
InChIKey: WPCWZULPRNURBM-UHFFFAOYSA-N
Target: WD repeat-containing protein 91 (SINGLE PROTEIN), Homo sapiens
UniProt: A4D1P6
Assay: Binding affinity to C-terminal His6-tagged truncated WDR91 (unknown origin) (P392 to A747 residues) expressed in baculovirus-infected Sf9 cells assessed as dissociation constant incubated for 72 to 96 hrs by SPR analysis
Measurement: Kd = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 384.86, ALogP 3.12, HBA 3, HBD 1, PSA 58.64, QED 0.86
Compound (SMILES): CN1CCC(CNC(=O)c2ccc(CN3CCN(c4nnc(NC(=O)Cc5ccccc5)s4)CC3)cc2)CC1
InChIKey: DWRFPKKIFBRTAR-UHFFFAOYSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Inhibition of GLS1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 547.73, ALogP 3.11, HBA 8, HBD 2, PSA 93.7, QED 0.43
Compound (SMILES): COc1ccc(NC(=O)c2ccccc2OCc2c(C)noc2C)cc1
InChIKey: IVHRQPGVODRTSU-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04828
Assay: Inhibition of AKR1C1 (unknown origin) incubated for 10 mins by fluorometric analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 352.39, ALogP 4.13, HBA 5, HBD 1, PSA 73.59, QED 0.72
Compound (SMILES): CS(=O)(=O)Nc1cc(Cl)c(Cl)c2ccc(C(=O)O)nc12
InChIKey: KEECUMCHPGTDME-UHFFFAOYSA-N
Target: Metallo-beta-lactamase type 2 (SINGLE PROTEIN), Bacteria
UniProt: C7C422
Assay: Inhibition of C-terminal 6His-tagged full length NDM-1 (unknown origin) expressed in Escherichia coli BL21-DE3 using nitrocefin as substrate incubated for 15 mins followed by substrate addition by absorbance based microplate reader analysis
Measurement: IC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 335.17, ALogP 2.61, HBA 4, HBD 2, PSA 96.36, QED 0.9
Compound (SMILES): CCc1cc(C(=O)O)cc2c1nc(CN1CCN(c3cccc(OCc4ccc(C#N)cc4F)n3)C=N1)n2C[C@@H]1CCO1
InChIKey: DRXIHAIBSCDJPZ-DEOSSOPVSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at N-terminal HA-tagged human GLP-1R expressed in HEK293 cells assessed as effect on intracellular cAMP accumulation incubated for 30 mins by LANCA ultra cAMP assay
Measurement: EC50 = 0.363 nM (pChEMBL 9.4399995803833)
Descriptors: MW 583.62, ALogP 4.34, HBA 10, HBD 1, PSA 129.1, QED 0.29
Compound (SMILES): COc1ccc(OS(=O)(=O)C2CC3OC2C(c2ccc(-n4cncn4)cc2)=C3c2ccc(O)cc2)cc1
InChIKey: SXEQYCSDUJXUEG-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha (unknown origin) assessed as inhibition constant
Measurement: Ki = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 517.56, ALogP 3.84, HBA 9, HBD 1, PSA 112.77, QED 0.37
Compound (SMILES): CCC[C@H](CCO)Nc1nc(N)nc2cnn(Cc3ncc(C4CCN(C5CCOCC5)CC4)cc3OC)c12
InChIKey: RZRJLAWKPZNKQG-OAQYLSRUSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 in HEK-Blue hTLR7 cells harboring SEAP reporter transgene incubated for 18 hrs by quanti-blue reagent based assay
Measurement: EC50 = 272 nM (pChEMBL 6.570000171661377)
Descriptors: MW 538.7, ALogP 3.18, HBA 11, HBD 3, PSA 136.47, QED 0.33
Compound (SMILES): Cc1[nH]c(C(=O)Nc2ccc(C(=O)NCCN)cc2OC(C)C)c(Cl)c1Cl.Cl
InChIKey: JKCOZXRKUPBXOI-UHFFFAOYSA-N
Target: DNA topoisomerase 2-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P11388
Assay: Inhibition of human DNA topoisomerase 2 alpha assessed as relaxation of supercoiled plasmid pNO1 DNA incubated for 30 mins by fluorescence based analysis
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 413.31, ALogP 3.36, HBA 4, HBD 4, PSA 109.24, QED 0.56
Compound (SMILES): O=C(NCCCCCCNc1nonc1/C(=N/O)Nc1ccc(F)c(Br)c1)c1ccc2nccn2c1
InChIKey: CGHBNLCYTYSIJV-UHFFFAOYSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Inhibition of recombinant NAMPT (unknown origin) incubated for 60 mins by SpectraMax microplate reader analysis
Measurement: IC50 = 57.7 nM (pChEMBL 7.239999771118164)
Descriptors: MW 559.4, ALogP 4.27, HBA 9, HBD 4, PSA 141.97, QED 0.07
Compound (SMILES): O=C1NC(N[C@@H]2CCCC[C@@H]2O)=N/C1=C\c1ccc2ncsc2c1
InChIKey: RUQXGVGYNKIGJD-JYPUUYBRSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of human CK1 epsilon using casein and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 342.42, ALogP 2.02, HBA 6, HBD 3, PSA 86.61, QED 0.73
Compound (SMILES): CCN(CC)c1ccc(-c2nc3ncncc3n2Cc2coc(C)n2)cn1
InChIKey: RGKGCPLZDTVQAE-UHFFFAOYSA-N
Target: Myc proto-oncogene protein (SINGLE PROTEIN), Homo sapiens
UniProt: P01106
Assay: Inhibition of human c-Myc in human Daudi cells assessed as decrease in c-Myc protein expression level incubated for 24 hrs by HTRF assay
Measurement: EC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 363.43, ALogP 3.08, HBA 8, HBD 0, PSA 85.76, QED 0.52
Compound (SMILES): O[C@@H](CNCC1COc2ccccc2O1)COc1cccc2cnccc12
InChIKey: LPDXLTWWYPTGHL-BHWOMJMDSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Agonist activity at human beta1-adrenergic receptor expressed in CHO-K1 cells co-expressing CRE-SPAP reporter gene assessed as CRE-SPAP production measured after 5 hrs incubation
Measurement: EC50 = 74.13 nM (pChEMBL 7.130000114440918)
Descriptors: MW 366.42, ALogP 2.4, HBA 6, HBD 2, PSA 72.84, QED 0.67
Compound (SMILES): Cc1cccn2c1nc1c3ccccc3nc(-c3ccccn3)c12
InChIKey: RPOBHFDVOWLTIF-UHFFFAOYSA-N
Target: DNA topoisomerase I (SINGLE PROTEIN), Leishmania donovani (strain BPK282A1)
UniProt: E9BRC0
Assay: Inhibition of Leishmania donovani Top1 assessed as relaxation of supercoiled pBluescript SK(+) DNA measured by agarose gel electrophoresis analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 310.36, ALogP 4.41, HBA 4, HBD 0, PSA 43.08, QED 0.46
Compound (SMILES): O=C(CNC(=O)c1ncc(-c2ccccc2)o1)NO
InChIKey: CVHXSSSJFXKKOF-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human HDAC1 using Boc-Lys (acetyl)-AMC as substrate pretreated with compound for 1 hrs followed by substrate addition measured after 1 hrs by microplate reader analysis
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 261.24, ALogP 0.58, HBA 5, HBD 3, PSA 104.46, QED 0.55
Compound (SMILES): COc1ccc(-c2ccnc3cc(C(=O)Nc4ccc(OCCN5CCOCC5)cc4)nn23)cc1OC
InChIKey: AJRYTPNAVBLXIW-UHFFFAOYSA-N
Target: Cystic fibrosis transmembrane conductance regulator (SINGLE PROTEIN), Homo sapiens
UniProt: P13569
Assay: Activation of human wild-type CFTR stably expressed in CHO-K1 cells co-expressing halide sensors YFP-H148Q/I152L assessed as CFTR-mediated iodide influx incubated for 10 mins by YFP fluorescence quenching assay
Measurement: EC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 503.56, ALogP 3.38, HBA 9, HBD 1, PSA 99.45, QED 0.37
Compound (SMILES): CCOC(=O)c1nc(NCC(C)OC)c2c(-c3ccc(F)cc3)noc2n1
InChIKey: BFXBEJWOEUTZIE-UHFFFAOYSA-N
Target: Solute carrier family 26 member 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXS9
Assay: Inhibition of SLC26A6 (unknown origin) expressed in rat FRT cells coexpressing YFP halide-sensing protein assessed as iodide-chloride exchange incubated for 2 sec by fluorescence quenching analysis
Measurement: IC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 374.37, ALogP 3.05, HBA 8, HBD 1, PSA 99.37, QED 0.63
Compound (SMILES): CC(C)(C)C[C@H](NC(=O)c1cc2ccccc2[nH]1)C(=O)N[C@H](C=O)C[C@@H]1CCNC1=O
InChIKey: UKRHQTNPJUCCTN-BXWFABGCSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of His/SUMO tagged SARS-CoV-2 main protease transfected in Escherichia coli BL21 (DE3) using Dabcyl-KTSAVLQSGFRKME-Edans as substrate preincubated for 30 mins followed by substrate addition by fluorescence based analysis
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 426.52, ALogP 1.91, HBA 4, HBD 4, PSA 120.16, QED 0.48
Compound (SMILES): CCN1CCC(NC(=O)c2ccc(COC3CCN(c4nnc(NC(=O)Cc5ccccc5)s4)CC3)cc2)CC1
InChIKey: TXLSPADCNIFESR-UHFFFAOYSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Inhibition of GLS1 (unknown origin)
Measurement: IC50 = 2550 nM (pChEMBL 5.590000152587891)
Descriptors: MW 562.74, ALogP 4.12, HBA 8, HBD 2, PSA 99.69, QED 0.38
Compound (SMILES): Cc1noc(C)c1-c1ncn(C)c1-c1ccnc2cc(F)ccc12
InChIKey: FOQLCYIBXICLES-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase NSD3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZ95
Assay: Inhibition of NSD3 PWWP1 domain (unknown origin) assessed as inhibition constant by SPR analysis
Measurement: Kd = 6800 nM (pChEMBL 5.170000076293945)
Descriptors: MW 322.34, ALogP 4.05, HBA 5, HBD 0, PSA 56.74, QED 0.56
Compound (SMILES): Cn1c([N+](=O)[O-])cnc1COc1cc(Cl)cc(-n2cc(-c3ccc[nH]c3=O)c(=O)n(-c3cccnc3)c2=O)c1
InChIKey: ORNUELPFJFKHHE-UHFFFAOYSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 main protease expressed in Escherichia coli using [NH2-C(EDANS)VNSTQSGLRK(DABCYL)M-COOH] FRET peptide as substrate pre-incubated for 20 mins followed by substrate addition enzyme activity measured every 5 mins for 120 mins by fluorescence assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 547.92, ALogP 2.61, HBA 11, HBD 1, PSA 159.94, QED 0.24
Compound (SMILES): Cn1ccc(-c2cn([C@@H]3O[C@H](C(=O)N[C@@H]4CCc5nc(N)sc5C4)[C@@H](O)[C@H]3O)c3ncnc(N)c23)n1
InChIKey: MKDMZRDYSAYRKH-GVFTWGKLSA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3 (unknown origin) using UCUGGACUAAA-biotin and 3H-SAM as substrates incubated for 30 mins and measured by TopCount scintillation counter method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 511.57, ALogP -0.25, HBA 13, HBD 5, PSA 192.25, QED 0.24
Compound (SMILES): O=C(O)c1ccc(CNC(=O)c2c3ccccc3nn2Cc2ccc(Cl)c(F)c2)cc1
InChIKey: OYRHAYDNOJRDRP-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Antagonist activity at human EP4 receptor transfected in HEK293 cells assessed as inhibition of PGE2-induced cAMP production measured for 30 mins by Glosensor cAMP assay
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 437.86, ALogP 4.51, HBA 4, HBD 2, PSA 84.22, QED 0.46