PP1 analog II [Ligand Id: 6028] activity data from GtoPdb and ChEMBL
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| ChEMBL ligand: CHEMBL573578 |
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| DB | Assay description | Assay Type | Standard value | Standard parameter | Original value | Original units | Original parameter | Reference |
|---|---|---|---|---|---|---|---|---|
| calcium/calmodulin-dependent protein kinase II alpha subunit/Calcium/calmodulin-dependent protein kinase type II subunit alpha in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4147] [GtoPdb: 1555] [UniProtKB: Q9UQM7] | ||||||||
| ChEMBL | Inhibition of CAMK2 F89G mutant | B | 8.1 | pIC50 | 8 | nM | IC50 | Nat Chem Biol (2005) 1: 130-142 [PMID:16408016] |
| Calmodulin-domain protein kinase 1 in Toxoplasma gondii (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1781862] [UniProtKB: Q9BJF5] | ||||||||
| ChEMBL | Inhibition of Toxoplasma gondii recombinant N-terminal hexahistidine tagged CDPK1 expressed in Escherichia coli using syntide-2 as substrate after 90 mins by luminescence based scintillation counter | B | 7.51 | pIC50 | 31 | nM | IC50 | ACS Med Chem Lett (2010) 1: 331-335 [PMID:21116453] |
| ChEMBL | Biological Assay: Most known kinase inhibitors bind in the ATP-binding pocket of the active site19,20. These inhibitors exploit many of the same hydrophobic contacts as the purine ring of ATP and make at least one conserved hydrogen bond to the hinge region. Potent inhibitors also occupy at least one hydrophobic pocket adjacent to the ATP-binding site. These additional hydrophobic interactions increase both binding affinity and target selectivity of the inhibitor because there is substantial heterogeneity among different kinases in these regions. Examination of the TgCDPK1 sequence in the vicinity of the ATP-binding pocket (FIG. 2b ) shows that it contains a glycine residue at a position that has been termed the gatekeeper residue because it constrains access to the ATP-binding site21-23. The glycine at this position in TgCDPK1 (Gly128) is expected to create a much larger pocket off the ATP-binding site than is typically seen in protein kinases and comparison of the TgCDPK1 structure with other kinases shows that this is indeed the case. This difference in the active site architectures can be exploited for design of selective inhibitors against TgCDPK1. | B | 7.51 | pIC50 | 31 | nM | IC50 | US-9765037-B2. Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases (2017) |
| ChEMBL | luminescent kinase assay: Inhibition of TgCDPK1 and CpCDPK1 was determined using a luminescent kinase assay which measures ATP depletion in the presence of the Syntide 2 peptide substrate (KinaseGlo). (U.S. Provisional Patent Application No. 61/299,286, and reference 9) Similar to TgCDPK1, exogenous calcium was necessary for CpCDPK1 to possess maximum catalytic activity (data not shown). Notably, both kinases were tested at the same ATP concentration which allows direct comparison of inhibitor potencies due to these enzymes possessing similar Kms for this cofactor. (20)Encouraged by the similar potency of inhibitor 3 against TgCDPK1 (IC50=150±20 nM) and CpCDPK1 (IC50=130±40 nM), pyrazolopyrimidine analogues that contain a naphthylmethylene group at the 3-position and various alkyl substituents at the 1-position were tested for their ability to inhibit both kinases. | B | 7.51 | pIC50 | 31 | nM | IC50 | US-10544104-B2. Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases (2020) |
| ChEMBL | luminescent kinase assay: Inhibition of TgCDPK1 and CpCDPK1 was determined using a luminescent kinase assay which measures ATP depletion in the presence of the Syntide 2 peptide substrate (KinaseGlo). (U.S. Provisional Patent Application No. 61/299,286, and reference 9) Similar to TgCDPK1, exogenous calcium was necessary for CpCDPK1 to possess maximum catalytic activity (data not shown). Notably, both kinases were tested at the same ATP concentration which allows direct comparison of inhibitor potencies due to these enzymes possessing similar Kms for this cofactor. (20)Encouraged by the similar potency of inhibitor 3 against TgCDPK1 (IC50=150±20 nM) and CpCDPK1 (IC50=130±40 nM), pyrazolopyrimidine analogues that contain a naphthylmethylene group at the 3-position and various alkyl substituents at the 1-position were tested for their ability to inhibit both kinases. | B | 7.51 | pIC50 | 31 | nM | IC50 | US-10544104-B2. Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases (2020) |
| protein kinase, cAMP-dependent, catalytic, alpha subunit/cAMP-dependent protein kinase catalytic subunit alpha in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4101] [GtoPdb: 1476] [UniProtKB: P17612] | ||||||||
| ChEMBL | Inhibition of PKA in the presence of 20uM ATP | B | 6.3 | pIC50 | 500 | nM | IC50 | Biochem J (2007) 408: 297-315 [PMID:17850214] |
| cyclin dependent kinase 12/Cyclin-dependent kinase 12 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3559692] [GtoPdb: 1965] [UniProtKB: Q9NYV4] | ||||||||
| ChEMBL | Inhibition of CDK12 (unknown origin) | B | 7 | pIC50 | 100 | nM | IC50 | Eur J Med Chem (2022) 240: 114603-114603 [PMID:35868123] |
| cyclin dependent kinase 2/Cyclin-dependent kinase 2 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL301] [GtoPdb: 1973] [UniProtKB: P24941] | ||||||||
| ChEMBL | Inhibition of wild type CDK2 | B | 4.54 | pIC50 | 29000 | nM | IC50 | Nat Chem Biol (2005) 1: 130-142 [PMID:16408016] |
| ChEMBL | Inhibition of CDK2 F80G mutant | B | 8.3 | pIC50 | 5 | nM | IC50 | Nat Chem Biol (2005) 1: 130-142 [PMID:16408016] |
| mitogen-activated protein kinase 8/Mitogen-activated protein kinase 8 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2276] [GtoPdb: 1496] [UniProtKB: P45983] | ||||||||
| ChEMBL | Inhibition of JNK-M108A in the presence of 20uM ATP | B | 6.6 | pIC50 | 250 | nM | IC50 | Biochem J (2007) 408: 297-315 [PMID:17850214] |
| ChEMBL | Inhibition of JNK-M108G in the presence of 20uM ATP | B | 6.85 | pIC50 | 140 | nM | IC50 | Biochem J (2007) 408: 297-315 [PMID:17850214] |
| LCK proto-oncogene, Src family tyrosine kinase/Proto-oncogene tyrosine-protein kinase LCK in Mouse (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2480] [GtoPdb: 2053] [UniProtKB: P06240] | ||||||||
| ChEMBL | Inhibition of Lck in the presence of 50uM ATP | B | 6.34 | pIC50 | 460 | nM | IC50 | Biochem J (2007) 408: 297-315 [PMID:17850214] |
| Proto-oncogene tyrosine-protein kinase Src in Chicken (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3655] [UniProtKB: P00523] | ||||||||
| ChEMBL | Inhibition of Src in the presence of 50uM ATP | B | 6.21 | pIC50 | 620 | nM | IC50 | Biochem J (2007) 408: 297-315 [PMID:17850214] |
| SRC proto-oncogene, non-receptor tyrosine kinase/Proto-oncogene tyrosine-protein kinase Src in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL267] [GtoPdb: 2206] [UniProtKB: P12931] | ||||||||
| ChEMBL | Inhibition Assay: Inhibition of human tyrosine kinases. | B | 5.66 | pIC50 | 2200 | nM | IC50 | US-9765037-B2. Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases (2017) |
| ChEMBL | luminescent kinase assay: Inhibition of TgCDPK1 and CpCDPK1 was determined using a luminescent kinase assay which measures ATP depletion in the presence of the Syntide 2 peptide substrate (KinaseGlo). (U.S. Provisional Patent Application No. 61/299,286, and reference 9) Similar to TgCDPK1, exogenous calcium was necessary for CpCDPK1 to possess maximum catalytic activity (data not shown). Notably, both kinases were tested at the same ATP concentration which allows direct comparison of inhibitor potencies due to these enzymes possessing similar Kms for this cofactor. (20)Encouraged by the similar potency of inhibitor 3 against TgCDPK1 (IC50=150±20 nM) and CpCDPK1 (IC50=130±40 nM), pyrazolopyrimidine analogues that contain a naphthylmethylene group at the 3-position and various alkyl substituents at the 1-position were tested for their ability to inhibit both kinases. | B | 5.66 | pIC50 | 2200 | nM | IC50 | US-10544104-B2. Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases (2020) |
| ChEMBL | KinaseGlo Assay: Kinase phosphorylation reactions were performed in a buffered medium containing 20 mM HEPES pH 7.5 (KOH), 0.1% BSA, 10 mM MgCl2, 1 mM EGTA (pH 7.2), plus or minus 2 mM CaCl2 14. The phosphorylation reaction mixture of 40 μM peptide substrate (Syntide-2, peptide sequence: Pro-Leu-Ala-Arg-Thr-Leu-Ser-Val-Ala-Gly-Leu-Pro-Gly-Lys-Lys (SEQ ID NO: 12)) (GenScript, Piscataway, USA), 19.48 nM of 14 TgCDPK1, 90 to 0.0005 μM serial dilutions of inhibitor in a total volume of 25 μl, was initiated by the addition of 10 μM ATP. The reaction was terminated after 30 minutes incubation at 30° C. by addition of excess EGTA (5 mM final concentration). Internal positive and negative controls were included in each assay run. | B | 5.66 | pIC50 | 2200 | nM | IC50 | US-11247972-B2. Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases (2022) |
| receptor interacting serine/threonine kinase 2/Receptor-interacting serine/threonine-protein kinase 2 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL5014] [GtoPdb: 2190] [UniProtKB: O43353] | ||||||||
| ChEMBL | Inhibition of RIP2 in the presence of 100uM ATP | B | 6.89 | pIC50 | 130 | nM | IC50 | Biochem J (2007) 408: 297-315 [PMID:17850214] |
| protein kinase D1/Serine/threonine-protein kinase D1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL3863] [GtoPdb: 1489] [UniProtKB: Q15139] | ||||||||
| ChEMBL | Inhibition of recombinant FLAG-tagged PKD1 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay | B | 5.99 | pIC50 | 1013 | nM | IC50 | Eur J Med Chem (2020) 205: 112638-112638 [PMID:32835918] |
| ChEMBL | Inhibition of PKD1 in the presence of 50uM ATP | B | 6.6 | pIC50 | 250 | nM | IC50 | Biochem J (2007) 408: 297-315 [PMID:17850214] |
| protein kinase D2/Serine/threonine-protein kinase D2 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL4900] [GtoPdb: 2173] [UniProtKB: Q9BZL6] | ||||||||
| ChEMBL | Inhibition of recombinant FLAG-tagged PKD2 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay | B | 6.1 | pIC50 | 786 | nM | IC50 | Eur J Med Chem (2020) 205: 112638-112638 [PMID:32835918] |
| protein kinase D3/Serine/threonine-protein kinase D3 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2595] [GtoPdb: 2174] [UniProtKB: O94806] | ||||||||
| ChEMBL | Inhibition of recombinant FLAG-tagged PKD3 (unknown origin) expressed in HEK293T cells using Syntide-2 as substrate measured after 15 mins by ADP-Glo assay | B | 6.21 | pIC50 | 616 | nM | IC50 | Eur J Med Chem (2020) 205: 112638-112638 [PMID:32835918] |
| ABL proto-oncogene 1, non-receptor tyrosine kinase/Tyrosine-protein kinase ABL1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1862] [GtoPdb: 1923] [UniProtKB: P00519] | ||||||||
| ChEMBL | Inhibition Assay: Inhibition of human tyrosine kinases. | B | 5.11 | pIC50 | 7700 | nM | IC50 | US-9765037-B2. Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases (2017) |
| ChEMBL | luminescent kinase assay: Inhibition of TgCDPK1 and CpCDPK1 was determined using a luminescent kinase assay which measures ATP depletion in the presence of the Syntide 2 peptide substrate (KinaseGlo). (U.S. Provisional Patent Application No. 61/299,286, and reference 9) Similar to TgCDPK1, exogenous calcium was necessary for CpCDPK1 to possess maximum catalytic activity (data not shown). Notably, both kinases were tested at the same ATP concentration which allows direct comparison of inhibitor potencies due to these enzymes possessing similar Kms for this cofactor. (20)Encouraged by the similar potency of inhibitor 3 against TgCDPK1 (IC50=150±20 nM) and CpCDPK1 (IC50=130±40 nM), pyrazolopyrimidine analogues that contain a naphthylmethylene group at the 3-position and various alkyl substituents at the 1-position were tested for their ability to inhibit both kinases. | B | 5.11 | pIC50 | 7700 | nM | IC50 | US-10544104-B2. Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases (2020) |
| ChEMBL | KinaseGlo Assay: Kinase phosphorylation reactions were performed in a buffered medium containing 20 mM HEPES pH 7.5 (KOH), 0.1% BSA, 10 mM MgCl2, 1 mM EGTA (pH 7.2), plus or minus 2 mM CaCl2 14. The phosphorylation reaction mixture of 40 μM peptide substrate (Syntide-2, peptide sequence: Pro-Leu-Ala-Arg-Thr-Leu-Ser-Val-Ala-Gly-Leu-Pro-Gly-Lys-Lys (SEQ ID NO: 12)) (GenScript, Piscataway, USA), 19.48 nM of 14 TgCDPK1, 90 to 0.0005 μM serial dilutions of inhibitor in a total volume of 25 μl, was initiated by the addition of 10 μM ATP. The reaction was terminated after 30 minutes incubation at 30° C. by addition of excess EGTA (5 mM final concentration). Internal positive and negative controls were included in each assay run. | B | 5.11 | pIC50 | 7700 | nM | IC50 | US-11247972-B2. Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases (2022) |
| ChEMBL | Inhibition of wild type c-Abl | B | 5.47 | pIC50 | 3400 | nM | IC50 | Nat Chem Biol (2005) 1: 130-142 [PMID:16408016] |
| ChEMBL | Inhibition of c-Abl T315A mutant | B | 6.92 | pIC50 | 120 | nM | IC50 | Nat Chem Biol (2005) 1: 130-142 [PMID:16408016] |
| C-terminal Src kinase/Tyrosine-protein kinase CSK in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL2634] [GtoPdb: 1994] [UniProtKB: P41240] | ||||||||
| ChEMBL | Inhibition of CSK in the presence of 20uM ATP | B | 6.29 | pIC50 | 510 | nM | IC50 | Biochem J (2007) 408: 297-315 [PMID:17850214] |
| FYN proto-oncogene, Src family tyrosine kinase/Tyrosine-protein kinase Fyn in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1841] [GtoPdb: 2026] [UniProtKB: P06241] | ||||||||
| ChEMBL | Inhibition of wild type c-Fyn | B | 6 | pIC50 | 1000 | nM | IC50 | Nat Chem Biol (2005) 1: 130-142 [PMID:16408016] |
ChEMBL data shown on this page come from version 36:
Zdrazil B, Felix E, Hunter F, Manners EJ, Blackshaw J, Corbett S, de Veij M, Ioannidis H, Lopez DM, Mosquera JF, Magarinos MP, Bosc N, Arcila R, Kizilören T, Gaulton A, Bento AP, Adasme MF, Monecke P, Landrum GA, Leach AR. (2024). The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods. Nucleic Acids Res., 52(D1). DOI: 10.1093/nar/gkad1004. [EPMCID:10767899] [PMID:37933841]
Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP. (2015) 'ChEMBL web services: streamlining access to drug discovery data and utilities.' Nucleic Acids Res., 43(W1). DOI: 10.1093/nar/gkv352. [EPMCID:25883136]
