GRK2 Inhibitor | CAS#24269-96-3 | GRK 2 inhibitor

MedKoo Cat#: 563192 | Name: GRK2 Inhibitor

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Description:

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

GRK2 Inhibitor is an inhibitor of GRK 2 (β-Adrenergic Receptor Kinase 1).

Chemical Structure

GRK2 Inhibitor

CAS#24269-96-3

Theoretical Analysis

MedKoo Cat#: 563192

Name: GRK2 Inhibitor

CAS#: 24269-96-3

Chemical Formula: C12H9NO6

Exact Mass: 263.0430

Molecular Weight: 263.21

Elemental Analysis: C, 54.76; H, 3.45; N, 5.32; O, 36.47

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 350.00	2 Weeks
10mg	USD 650.00	2 Weeks

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Related CAS #

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Synonym

GRK2 Inhibitor; βARK1 Inhibitor;

IUPAC/Chemical Name

5-[2-(5-Nitro-furan-2-yl)-vinyl]-furan-2-carboxylic acid methyl ester

InChi Key

YDJPHSNZGRVPCK-NSCUHMNNSA-N

InChi Code

InChI=1S/C12H9NO6/c1-17-12(14)10-6-4-8(18-10)2-3-9-5-7-11(19-9)13(15)16/h2-7H,1H3/b3-2+

SMILES Code

O=C(C1=CC=C(/C=C/C2=CC=C([N+]([O-])=O)O2)O1)OC

Appearance

Solid powder

Purity

>95% (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

Shelf Life

>3 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

2934.99.03.00

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

GRK2 Inhibitor 1 (methyl 5-[2-(5-nitro-2-furyl)vinyl]-2-furoate) is a GRK2 (β-ARK1) inhibitor.

In vitro activity:

TBD

In vivo activity:

In the present study, this study further characterized this phenomenon by use of extracellular recordings in brain slices to examine whether DIR is linked to G protein-coupled receptor kinase-2 (GRK2) or dynamin by assessing DIR in the presence of antagonists of these enzymes. DIR was blocked by β-ARK1 inhibitor, which inhibits GRK2, and by dynasore, which blocks dynamin. Reference: J Pharmacol Exp Ther. 2013 Jan;344(1):253-63. https://pubmed.ncbi.nlm.nih.gov/23019137/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	113.98
	DMSO	35.8	136.15
	DMSO:PBS (pH 7.2) (1:2)	0.3	1.14

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 263.21 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. Taguchi K, Matsumoto T, Kamata K, Kobayashi T. Inhibitor of G protein-coupled receptor kinase 2 normalizes vascular endothelial function in type 2 diabetic mice by improving β-arrestin 2 translocation and ameliorating Akt/eNOS signal dysfunction. Endocrinology. 2012 Jul;153(7):2985-96. doi: 10.1210/en.2012-1101. Epub 2012 May 11. PMID: 22581458. 2. Nimitvilai S, McElvain MA, Brodie MS. Reversal of dopamine D2 agonist-induced inhibition of ventral tegmental area neurons by Gq-linked neurotransmitters is dependent on protein kinase C, G protein-coupled receptor kinase, and dynamin. J Pharmacol Exp Ther. 2013 Jan;344(1):253-63. doi: 10.1124/jpet.112.199844. Epub 2012 Sep 27. PMID: 23019137; PMCID: PMC3533415.

In vitro protocol:

TBD

In vivo protocol:

1: Wang HJ, Gu HX, Eijkelkamp N, Heijnen CJ, Kavelaars A. Low GRK2 Underlies Hyperalgesic Priming by Glial Cell-Derived Neurotrophic Factor. Front Pharmacol. 2018 Jun 5;9:592. doi: 10.3389/fphar.2018.00592. eCollection 2018. PubMed PMID: 29922165; PubMed Central PMCID: PMC5996251. 2: Crassini K, Pyke T, Shen Y, Stevenson WS, Christopherson RI, Mulligan SP, Best OG. Inhibition of the Raf-1 kinase inhibitory protein (RKIP) by locostatin induces cell death and reduces the CXCR4-mediated migration of chronic lymphocytic leukemia cells. Leuk Lymphoma. 2018 Jun 18:1-12. doi: 10.1080/10428194.2018.1455974. [Epub ahead of print] PubMed PMID: 29911936. 3: Yu Q, Gratzke C, Wang Y, Herlemann A, Strittmatter F, Rutz B, Stief CG, Hennenberg M. Inhibition of prostatic smooth muscle contraction by the inhibitor of G protein-coupled receptor kinase 2/3, CMPD101. Eur J Pharmacol. 2018 Jul 15;831:9-19. doi: 10.1016/j.ejphar.2018.04.022. Epub 2018 Apr 23. PubMed PMID: 29698717. 4: Im YN, Lee YD, Park JS, Kim HK, Im SY, Song HR, Lee HK, Han MK. GPCR Kinase (GRK)-2 Is a Key Negative Regulator of Itch: l-Glutamine Attenuates Itch via a Rapid Induction of GRK2 in an ERK-Dependent Way. J Invest Dermatol. 2018 Mar 9. pii: S0022-202X(18)30220-3. doi: 10.1016/j.jid.2018.02.036. [Epub ahead of print] PubMed PMID: 29530536. 5: Kawakami M, Hattori M, Ohashi W, Fujimori T, Hattori K, Takebe M, Tomita K, Yokoo H, Matsuda N, Yamazaki M, Hattori Y. Role of G protein-coupled receptor kinase 2 in oxidative and nitrosative stress-related neurohistopathological changes in a mouse model of sepsis-associated encephalopathy. J Neurochem. 2018 Mar 3. doi: 10.1111/jnc.14329. [Epub ahead of print] PubMed PMID: 29500815. 6: Taguchi K, Bessho N, Hasegawa M, Narimatsu H, Matsumoto T, Kobayashi T. Co-treatment with clonidine and a GRK2 inhibitor prevented rebound hypertension and endothelial dysfunction after withdrawal in diabetes. Hypertens Res. 2018 Apr;41(4):263-274. doi: 10.1038/s41440-018-0016-6. Epub 2018 Feb 20. PubMed PMID: 29463871. 7: Qi X, Guo Y, Song Y, Yu C, Zhao L, Fang L, Kong D, Zhao J, Gao L. Follicle-stimulating hormone enhances hepatic gluconeogenesis by GRK2-mediated AMPK hyperphosphorylation at Ser485 in mice. Diabetologia. 2018 May;61(5):1180-1192. doi: 10.1007/s00125-018-4562-x. Epub 2018 Feb 13. PubMed PMID: 29442133. 8: Pusapati GV, Kong JH, Patel BB, Gouti M, Sagner A, Sircar R, Luchetti G, Ingham PW, Briscoe J, Rohatgi R. G protein-coupled receptors control the sensitivity of cells to the morphogen Sonic Hedgehog. Sci Signal. 2018 Feb 6;11(516). pii: eaao5749. doi: 10.1126/scisignal.aao5749. PubMed PMID: 29438014; PubMed Central PMCID: PMC5828112. 9: 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. PubMed PMID: 29070696; PubMed Central PMCID: PMC5691592. 10: Zhang QH, Hao JW, Li GL, Ji XJ, Yao XD, Dong N, Yao YM. Proinflammatory switch from Gαs to Gαi signaling by Glucagon-like peptide-1 receptor in murine splenic monocyte following burn injury. Inflamm Res. 2018 Feb;67(2):157-168. doi: 10.1007/s00011-017-1104-9. Epub 2017 Oct 11. PubMed PMID: 29022064. 11: Guo S, Carter RL, Grisanti LA, Koch WJ, Tilley DG. Impact of paroxetine on proximal β-adrenergic receptor signaling. Cell Signal. 2017 Oct;38:127-133. doi: 10.1016/j.cellsig.2017.07.006. Epub 2017 Jul 12. PubMed PMID: 28711716; PubMed Central PMCID: PMC5646168. 12: Okawa T, Aramaki Y, Yamamoto M, Kobayashi T, Fukumoto S, Toyoda Y, Henta T, Hata A, Ikeda S, Kaneko M, Hoffman ID, Sang BC, Zou H, Kawamoto T. Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure. J Med Chem. 2017 Aug 24;60(16):6942-6990. doi: 10.1021/acs.jmedchem.7b00443. Epub 2017 Aug 3. PubMed PMID: 28699740. 13: Dal-Secco D, DalBó S, Lautherbach NES, Gava FN, Celes MRN, Benedet PO, Souza AH, Akinaga J, Lima V, Silva KP, Kiguti LRA, Rossi MA, Kettelhut IC, Pupo AS, Cunha FQ, Assreuy J. Cardiac hyporesponsiveness in severe sepsis is associated with nitric oxide-dependent activation of G protein receptor kinase. Am J Physiol Heart Circ Physiol. 2017 Jul 1;313(1):H149-H163. doi: 10.1152/ajpheart.00052.2016. Epub 2017 May 19. PubMed PMID: 28526706. 14: Wang Q, Wang L, Wu L, Zhang M, Hu S, Wang R, Han Y, Wu Y, Zhang L, Wang X, Sun W, Wei W. Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis. Sci Rep. 2017 Mar 28;7:45364. doi: 10.1038/srep45364. PubMed PMID: 28349925; PubMed Central PMCID: PMC5368980. 15: Waldschmidt HV, Homan KT, Cato MC, Cruz-Rodríguez O, Cannavo A, Wilson MW, Song J, Cheung JY, Koch WJ, Tesmer JJ, Larsen SD. Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine. J Med Chem. 2017 Apr 13;60(7):3052-3069. doi: 10.1021/acs.jmedchem.7b00112. Epub 2017 Mar 29. PubMed PMID: 28323425; PubMed Central PMCID: PMC5641445. 16: Dela Paz NG, Melchior B, Frangos JA. Shear stress induces Gα(q/11) activation independently of G protein-coupled receptor activation in endothelial cells. Am J Physiol Cell Physiol. 2017 Apr 1;312(4):C428-C437. doi: 10.1152/ajpcell.00148.2016. Epub 2017 Feb 1. PubMed PMID: 28148497; PubMed Central PMCID: PMC5407018. 17: Ge XY, Fang SP, Zhou M, Luo J, Wei J, Wen XP, Yan XD, Zou Z. TLR4-dependent internalization of CX3CR1 aggravates sepsis-induced immunoparalysis. Am J Transl Res. 2016 Dec 15;8(12):5696-5705. eCollection 2016. PubMed PMID: 28078040; PubMed Central PMCID: PMC5209520. 18: Wang Q, Liu Y, Fu Q, Xu B, Zhang Y, Kim S, Tan R, Barbagallo F, West T, Anderson E, Wei W, Abel ED, Xiang YK. Inhibiting Insulin-Mediated β2-Adrenergic Receptor Activation Prevents Diabetes-Associated Cardiac Dysfunction. Circulation. 2017 Jan 3;135(1):73-88. doi: 10.1161/CIRCULATIONAHA.116.022281. Epub 2016 Nov 4. PubMed PMID: 27815373; PubMed Central PMCID: PMC5302024. 19: Tian X, Wang Q, Guo R, Xu L, Chen QM, Hou Y. Effects of paroxetine-mediated inhibition of GRK2 expression on depression and cardiovascular function in patients with myocardial infarction. Neuropsychiatr Dis Treat. 2016 Sep 13;12:2333-2341. eCollection 2016. PubMed PMID: 27695334; PubMed Central PMCID: PMC5028169. 20: Rajkumar K, Nichita A, Anoor PK, Raju S, Singh SS, Burgula S. Understanding perspectives of signalling mechanisms regulating PEBP1 function. Cell Biochem Funct. 2016 Aug;34(6):394-403. doi: 10.1002/cbf.3198. Epub 2016 Jul 7. Review. PubMed PMID: 27385268.