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

GSK180736A
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 522708

CAS#: 817194-38-0

Description: 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

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 522708
Name: GSK180736A
CAS#: 817194-38-0
Chemical Formula: C19H16FN5O2
Exact Mass: 365.13
Molecular Weight: 365.368
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	2 Weeks
100mg	USD 450	2 Weeks
200mg	USD 650	2 Weeks
500mg	USD 1450	2 Weeks
1g	USD 2250	2 Weeks
2g	USD 3950	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

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:

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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/

Solubility Data

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

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:	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 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.

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Reconstitution Calculator

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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.

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