GSK180736A

GSK180736A is potent and selective inhibitor of GRK2 with an IC50 of 0.77 μM25 and >100-fold selectivity over other GRKs. It is a weak inhibitor of PKA with an IC50 of 30 μM, but highly potent against ROCK1 (IC50 = 100 nM).

Product information

CAS Number: 817194-38-0

Molecular Weight: 365.36

Formula: C19H16FN5O2

Chemical Name: 4-(4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide

Smiles: CC1NC(=O)NC(C=1C(=O)NC1C=C2C=NNC2=CC=1)C1C=CC(F)=CC=1

InChiKey: HEAIGWIZTYAQTC-UHFFFAOYSA-N

InChi: InChI=1S/C19H16FN5O2/c1-10-16(17(24-19(27)22-10)11-2-4-13(20)5-3-11)18(26)23-14-6-7-15-12(8-14)9-21-25-15/h2-9,17H,1H3,(H,21,25)(H,23,26)(H2,22,24,27)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

GSK180736A is a compound structurally similar to paroxetine that is developed as a ROCK inhibitor, is shown to be an even more potent and selective inhibitor of GRK2 with an IC50 of 0.77 μM and more than 100-fold selectivity over other GRKs. ROCK1 is a potential therapeutic target in the treatment of cardiovascular diseases such as hypertension. GSK180736A is a weak inhibitor of PKA with an IC50 of 30 μM, but highly potent against ROCK1 (IC50=100 nM).

References:

1. Homan KT, Larimore KM, Elkins JM, Szklarz M, Knapp S, Tesmer JJ.Identification and structure-function analysis of subfamily selective Gprotein-coupled receptor kinase inhibitors. ACS Chem Biol. 2015 Jan16;10(1):310-9. doi: 10.1021/cb5006323. Epub 2014 Oct 3. PubMed PMID: 25238254; PubMed Central PMCID: PMC4301037.
2. Homan KT, Waldschmidt HV, Glukhova A, Cannavo A, Song J, Cheung JY, Koch WJ, Larsen SD, Tesmer JJ. Crystal Structure of G Protein-coupled Receptor Kinase 5 in Complex with a Rationally Designed Inhibitor. J Biol Chem. 2015 Aug21;290(34):20649-59. doi: 10.1074/jbc.M115.647370. Epub 2015 Jun 1. PubMed PMID: 26032411; PubMed Central PMCID: PMC4543626.
3. Waldschmidt HV, Homan KT, Cruz-Rodriguez O, Cato MC, Waninger-Saroni J,Larimore KM, Cannavo A, Song J, Cheung JY, Kirchhoff PD, Koch WJ, Tesmer JJ,Larsen SD. Structure-Based Design, Synthesis and Biological Evaluation of HighlySelective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors. J Med Chem.2016 Apr 6. [Epub ahead of print] PubMed PMID: 27050625.

Products are for research use only. Not for human use.