GSK180736A | CAS#817194-38-0 | GRK2 inhibitor

MedKoo Cat#: 522708 | Name: GSK180736A

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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).

Chemical Structure

GSK180736A

CAS#817194-38-0

Theoretical Analysis

MedKoo Cat#: 522708

Name: GSK180736A

CAS#: 817194-38-0

Chemical Formula: C19H16FN5O2

Exact Mass: 365.1288

Molecular Weight: 365.37

Elemental Analysis: C, 62.46; H, 4.41; F, 5.20; N, 19.17; O, 8.76

Price and Availability

Size	Price	Availability
50mg	USD 250.00	2 Weeks
100mg	USD 450.00	2 Weeks
200mg	USD 650.00	2 Weeks
500mg	USD 1,450.00	2 Weeks
1g	USD 2,250.00	2 Weeks
2g	USD 3,950.00	2 Weeks

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Related CAS #

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Synonym

GSK180736A; GSK-180736A; GSK 180736A.

IUPAC/Chemical Name

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

InChi Key

HEAIGWIZTYAQTC-UHFFFAOYSA-N

InChi Code

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)

SMILES Code

CC1=C(C(NC(=O)N1)C2=CC=C(C=C2)F)C(=O)NC3=CC4=C(C=C3)NN=C4

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

GSK180736A is potent Rho-associated coiled-coil kinase 1 (ROCK1) inhibitor with an IC50 of 100 nM. GSK180736A is also a selective and ATP-competitive G protein-coupled receptor kinase 2 (GRK2) inhibitor with an IC50 of 0.77 μM.

In vitro activity:

GSK180736A, developed as a Rho-associated coiled-coil kinase 1 (ROCK1) inhibitor, was identified as an inhibitor of GRK2 and co-crystallized in the active site. Reference: J Med Chem. 2016 Apr 28;59(8):3793-807. https://pubmed.ncbi.nlm.nih.gov/27050625/

In vivo activity:

A new inhibitor, CCG258747, which is based on paroxetine, demonstrates increased potency against the GRK2 subfamily and favorable pharmacokinetic parameters in mice. Reference: Mol Pharmacol. 2020 Jun;97(6):392-401. https://pubmed.ncbi.nlm.nih.gov/32234810/

	Solvent	mg/mL	mM
Solubility
	DMSO	57.7	157.83
	Ethanol	3.0	8.21

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 365.37 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Bouley R, Waldschmidt HV, Cato MC, Cannavo A, Song J, Cheung JY, Yao XQ, Koch WJ, Larsen SD, Tesmer JJG. Structural Determinants Influencing the Potency and Selectivity of Indazole-Paroxetine Hybrid G Protein-Coupled Receptor Kinase 2 Inhibitors. Mol Pharmacol. 2017 Dec;92(6):707-717. doi: 10.1124/mol.117.110130. Epub 2017 Oct 25. PMID: 29070696; PMCID: PMC5691592. 2. Waldschmidt HV, Homan KT, Cruz-Rodríguez 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 Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors. J Med Chem. 2016 Apr 28;59(8):3793-807. doi: 10.1021/acs.jmedchem.5b02000. Epub 2016 Apr 13. PMID: 27050625; PMCID: PMC4890168.

In vitro protocol:

In vivo protocol:

1. Bouley RA, Weinberg ZY, Waldschmidt HV, Yen YC, Larsen SD, Puthenveedu MA, Tesmer JJG. A New Paroxetine-Based GRK2 Inhibitor Reduces Internalization of the μ-Opioid Receptor. Mol Pharmacol. 2020 Jun;97(6):392-401. doi: 10.1124/mol.119.118661. Epub 2020 Mar 31. PMID: 32234810; PMCID: PMC7237867.

1: 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 Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors. J Med Chem. 2016 Apr 6. [Epub ahead of print] PubMed PMID: 27050625. 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 Aug 21;290(34):20649-59. doi: 10.1074/jbc.M115.647370. Epub 2015 Jun 1. PubMed PMID: 26032411; PubMed Central PMCID: PMC4543626. 3: Homan KT, Larimore KM, Elkins JM, Szklarz M, Knapp S, Tesmer JJ. Identification and structure-function analysis of subfamily selective G protein-coupled receptor kinase inhibitors. ACS Chem Biol. 2015 Jan 16;10(1):310-9. doi: 10.1021/cb5006323. Epub 2014 Oct 3. PubMed PMID: 25238254; PubMed Central PMCID: PMC4301037.