GSK-7975A | CAS#1253186-56-9 | ORAI1 inhibitor

MedKoo Cat#: 522591 | Name: GSK-7975A

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Description:

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

GSK-7975A is an potent and orally active inhibitors of ORAI1 (calcium release-activated calcium modulator ). GSK-7975A prevents Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models. GSK-7975A inhibited toxin-induced activation of ORAI1 and/or activation of Ca(2+) currents after Ca(2+) release, in a concentration-dependent manner, in mouse and human pancreatic acinar cells (inhibition >90% of the levels observed in control cells). ORAI1 inhibitors might be developed for the treatment of patients with pancreatitis.

Chemical Structure

GSK-7975A

CAS#1253186-56-9

Theoretical Analysis

MedKoo Cat#: 522591

Name: GSK-7975A

CAS#: 1253186-56-9

Chemical Formula: C18H12F5N3O2

Exact Mass: 397.0850

Molecular Weight: 397.31

Elemental Analysis: C, 54.42; H, 3.04; F, 23.91; N, 10.58; O, 8.05

Price and Availability

Size	Price	Availability
100mg	USD 450.00	2 Weeks
200mg	USD 750.00	2 Weeks
500mg	USD 1,450.00	2 Weeks

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Synonym

GSK-7975A; GSK 7975A; GSK7975A; GSK-7975; GSK 7975; GSK7975.

IUPAC/Chemical Name

2,6-difluoro-N-(1-(4-hydroxy-2-(trifluoromethyl)benzyl)-1H-pyrazol-3-yl)benzamide

InChi Key

CPYTVBALBFSXSH-UHFFFAOYSA-N

InChi Code

InChI=1S/C18H12F5N3O2/c19-13-2-1-3-14(20)16(13)17(28)24-15-6-7-26(25-15)9-10-4-5-11(27)8-12(10)18(21,22)23/h1-8,27H,9H2,(H,24,25,28)

SMILES Code

O=C(NC1=NN(CC2=CC=C(O)C=C2C(F)(F)F)C=C1)C3=C(F)C=CC=C3F

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:

GSK-7975A is a potent and orally available CRAC channel inhibitor.

In vitro activity:

Potential translational applications of SOCE inhibition as a treatment for clinical acute pancreatitis were evaluated by examination of the effects of GSK-7975A or CM_128 on isolated human pancreatic acinar cells. GSK-7975A (10–50 μmol/L) inhibited SOCE in these cells (Figure 1A and B). Reference: Gastroenterology. 2015 Aug;149(2):481-92.e7. https://pubmed.ncbi.nlm.nih.gov/25917787/

In vivo activity:

Increasing concentrations of GSK (GSK-7975A) (from 2.6 to 31.8 mg/kg) were injected in neonatal mice at P3, P4, and P5, and retinal vessel formation was analyzed at P6. Figure 3A shows that vessel development was attenuated in the presence of increasing concentration of GSK. Reference: Front Cell Dev Biol. 2021 Apr 20;9:683097. https://pubmed.ncbi.nlm.nih.gov/33748129/

	Solvent	mg/mL	mM
Solubility
	DMSO	90.0	226.53

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 397.31 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. Wen L, Voronina S, Javed MA, Awais M, Szatmary P, Latawiec D, Chvanov M, Collier D, Huang W, Barrett J, Begg M, Stauderman K, Roos J, Grigoryev S, Ramos S, Rogers E, Whitten J, Velicelebi G, Dunn M, Tepikin AV, Criddle DN, Sutton R. Inhibitors of ORAI1 Prevent Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models. Gastroenterology. 2015 Aug;149(2):481-92.e7. doi: 10.1053/j.gastro.2015.04.015. Epub 2015 Apr 25. PMID: 25917787; PMCID: PMC4556985. 2. Rice LV, Bax HJ, Russell LJ, Barrett VJ, Walton SE, Deakin AM, Thomson SA, Lucas F, Solari R, House D, Begg M. Characterization of selective Calcium-Release Activated Calcium channel blockers in mast cells and T-cells from human, rat, mouse and guinea-pig preparations. Eur J Pharmacol. 2013 Mar 15;704(1-3):49-57. doi: 10.1016/j.ejphar.2013.02.022. Epub 2013 Feb 27. PMID: 23454522. 3. Galeano-Otero I, Del Toro R, Khatib AM, Rosado JA, Ordóñez-Fernández A, Smani T. SARAF and Orai1 Contribute to Endothelial Cell Activation and Angiogenesis. Front Cell Dev Biol. 2021 Mar 4;9:639952. doi: 10.3389/fcell.2021.639952. Erratum in: Front Cell Dev Biol. 2021 Apr 20;9:683097. PMID: 33748129; PMCID: PMC7970240

In vitro protocol:

In vivo protocol:

1. Galeano-Otero I, Del Toro R, Khatib AM, Rosado JA, Ordóñez-Fernández A, Smani T. SARAF and Orai1 Contribute to Endothelial Cell Activation and Angiogenesis. Front Cell Dev Biol. 2021 Mar 4;9:639952. doi: 10.3389/fcell.2021.639952. Erratum in: Front Cell Dev Biol. 2021 Apr 20;9:683097. PMID: 33748129; PMCID: PMC7970240

1: Duffy SM, Ashmole I, Smallwood DT, Leyland ML, Bradding P. Orai/CRACM1 and KCa3.1 ion channels interact in the human lung mast cell plasma membrane. Cell Commun Signal. 2015 Jul 16;13:32. doi: 10.1186/s12964-015-0112-z. PubMed PMID: 26177720; PubMed Central PMCID: PMC4504158. 2: Wen L, Voronina S, Javed MA, Awais M, Szatmary P, Latawiec D, Chvanov M, Collier D, Huang W, Barrett J, Begg M, Stauderman K, Roos J, Grigoryev S, Ramos S, Rogers E, Whitten J, Velicelebi G, Dunn M, Tepikin AV, Criddle DN, Sutton R. Inhibitors of ORAI1 Prevent Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models. Gastroenterology. 2015 Aug;149(2):481-92.e7. doi: 10.1053/j.gastro.2015.04.015. Epub 2015 Apr 25. PubMed PMID: 25917787; PubMed Central PMCID: PMC4556985. 3: Voronina S, Collier D, Chvanov M, Middlehurst B, Beckett AJ, Prior IA, Criddle DN, Begg M, Mikoshiba K, Sutton R, Tepikin AV. The role of Ca2+ influx in endocytic vacuole formation in pancreatic acinar cells. Biochem J. 2015 Feb 1;465(3):405-12. doi: 10.1042/BJ20140398. PubMed PMID: 25370603; PubMed Central PMCID: PMC4303308. 4: Chaudhari S, Wu P, Wang Y, Ding Y, Yuan J, Begg M, Ma R. High glucose and diabetes enhanced store-operated Ca(2+) entry and increased expression of its signaling proteins in mesangial cells. Am J Physiol Renal Physiol. 2014 May 1;306(9):F1069-80. doi: 10.1152/ajprenal.00463.2013. Epub 2014 Mar 12. PubMed PMID: 24623143; PubMed Central PMCID: PMC4010683. 5: Gerasimenko JV, Gryshchenko O, Ferdek PE, Stapleton E, Hébert TO, Bychkova S, Peng S, Begg M, Gerasimenko OV, Petersen OH. Ca2+ release-activated Ca2+ channel blockade as a potential tool in antipancreatitis therapy. Proc Natl Acad Sci U S A. 2013 Aug 6;110(32):13186-91. doi: 10.1073/pnas.1300910110. Epub 2013 Jul 22. PubMed PMID: 23878235; PubMed Central PMCID: PMC3740877. 6: Rice LV, Bax HJ, Russell LJ, Barrett VJ, Walton SE, Deakin AM, Thomson SA, Lucas F, Solari R, House D, Begg M. Characterization of selective Calcium-Release Activated Calcium channel blockers in mast cells and T-cells from human, rat, mouse and guinea-pig preparations. Eur J Pharmacol. 2013 Mar 15;704(1-3):49-57. doi: 10.1016/j.ejphar.2013.02.022. Epub 2013 Feb 27. PubMed PMID: 23454522. 7: Derler I, Schindl R, Fritsch R, Heftberger P, Riedl MC, Begg M, House D, Romanin C. The action of selective CRAC channel blockers is affected by the Orai pore geometry. Cell Calcium. 2013 Feb;53(2):139-51. doi: 10.1016/j.ceca.2012.11.005. Epub 2012 Dec 5. PubMed PMID: 23218667; PubMed Central PMCID: PMC3580291. 8: van Kruchten R, Braun A, Feijge MA, Kuijpers MJ, Rivera-Galdos R, Kraft P, Stoll G, Kleinschnitz C, Bevers EM, Nieswandt B, Heemskerk JW. Antithrombotic potential of blockers of store-operated calcium channels in platelets. Arterioscler Thromb Vasc Biol. 2012 Jul;32(7):1717-23. doi: 10.1161/ATVBAHA.111.243907. Epub 2012 May 10. PubMed PMID: 22580895. 9: Ashmole I, Duffy SM, Leyland ML, Morrison VS, Begg M, Bradding P. CRACM/Orai ion channel expression and function in human lung mast cells. J Allergy Clin Immunol. 2012 Jun;129(6):1628-35.e2. doi: 10.1016/j.jaci.2012.01.070. Epub 2012 Mar 10. PubMed PMID: 22409987; PubMed Central PMCID: PMC3526795.