GSK-7975A - CAS 1253186-56-9
Catalog number: B0084-475226
Category: Inhibitor
Not Intended for Therapeutic Use. For research use only.
Molecular Formula:
C18H12F5N3O2
Molecular Weight:
397.31
COA:
Inquire
Targets:
Others
Description:
This active molecular is a calcium release-activated calcium modulator (ORAI1) inhibitor. GSK-7975A inhibited toxin-induced activation of ORAI1 and/or activation of Ca(2+) currents after Ca(2+) release in mouse and human pancreatic acinar cells. GSK-7975A may be used for the treatment of pancreatitis in the future.
Ordering Information
Catalog Number Size Price Stock Quantity
B0084-475226 50 mg $598 In stock
Bulk Inquiry
Purity:
98%
Appearance:
Powder
Synonyms:
SCHEMBL705705; AOB4124; CPYTVBALBFSXSH-UHFFFAOYSA-N;2,6-difluoro-N-[1-[[4-hydroxy-2-(trifluoromethyl)phenyl]methyl]pyrazol-3-yl]benzamide
Solubility:
Soluble in DMSO
Storage:
-20°C Freezer
MSDS:
Inquire
Application:
pancreatitis
Quality Standard:
In-house standard
Shelf Life:
2 month in rt, long time
Quantity:
Milligrams-Grams
InChIKey:
CPYTVBALBFSXSH-UHFFFAOYSA-N
InChI:
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)
Canonical SMILES:
C1=CC(=C(C(=C1)F)C(=O)NC2=NN(C=C2)CC3=C(C=C(C=C3)O)C(F)(F)F)F
Current Developer:
GSK
1.Store-operated calcium entry suppressed the TGF-β1/Smad3 signaling pathway in glomerular mesangial cells.
Chaudhari S;Li W;Wang Y;Jiang H;Ma Y;Davis ME;Zuckerman JE;Ma R Am J Physiol Renal Physiol. 2017 Sep 1;313(3):F729-F739. doi: 10.1152/ajprenal.00483.2016. Epub 2017 Jun 21.
Our previous study demonstrated that the abundance of extracellular matrix proteins was suppressed by store-operated Ca;2+; entry (SOCE) in mesangial cells (MCs). The present study was conducted to investigate the underlying mechanism focused on the transforming growth factor-β1 (TGF-β1)/Smad3 pathway, a critical pathway for ECM expansion in diabetic kidneys. We hypothesized that SOCE suppressed ECM protein expression by inhibiting this pathway in MCs. In cultured human MCs, we observed that TGF-β1 (5 ng/ml for 15 h) significantly increased Smad3 phosphorylation, as evaluated by immunoblot. However, this response was markedly inhibited by thapsigargin (1 µM), a classical activator of store-operated Ca;2+; channels. Consistently, both immunocytochemistry and immunoblot showed that TGF-β1 significantly increased nuclear translocation of Smad3, which was prevented by pretreatment with thapsigargin. Importantly, the thapsigargin effect was reversed by lanthanum (La;3+;; 5 µM) and GSK-7975A (10 µM), both of which are selective blockers of store-operated Ca;2+; channels. Furthermore, knockdown of Orai1, the pore-forming subunit of the store-operated Ca;2+; channels, significantly augmented TGF-β1-induced Smad3 phosphorylation.
2.Ca
Drumm BT;Rembetski BE;Cobine CA;Baker SA;Sergeant GP;Hollywood MA;Thornbury KD;Sanders KM J Physiol. 2018 Apr 15;596(8):1433-1466. doi: 10.1113/JP275719.
KEY POINTS: ;Contraction of urethral smooth muscle cells (USMCs) contributes to urinary continence. Ca;2+; signalling in USMCs was investigated in intact urethral muscles using a genetically encoded Ca;2+; sensor, GCaMP3, expressed selectively in USMCs. USMCs were spontaneously active in situ, firing intracellular Ca;2+; waves that were asynchronous at different sites within cells and between adjacent cells. Spontaneous Ca;2+; waves in USMCs were myogenic but enhanced by adrenergic or purinergic agonists and decreased by nitric oxide. Ca;2+; waves arose from inositol trisphosphate type 1 receptors and ryanodine receptors, and Ca;2+; influx by store-operated calcium entry was required to maintain Ca;2+; release events. Ca;2+; release and development of Ca;2+; waves appear to be the primary source of Ca;2+; for excitation-contraction coupling in the mouse urethra, and no evidence was found that voltage-dependent Ca;2+; entry via L-type or T-type channels was required for responses to α adrenergic responses.;ABSTRACT: ;Urethral smooth muscle cells (USMCs) generate myogenic tone and contribute to urinary continence. Currently, little is known about Ca;2+; signalling in USMCs in situ, and therefore little is known about the source(s) of Ca;2+; required for excitation-contraction coupling.
3.Characterization of selective Calcium-Release Activated Calcium channel blockers in mast cells and T-cells from human, rat, mouse and guinea-pig preparations.
Rice LV;Bax HJ;Russell LJ;Barrett VJ;Walton SE;Deakin AM;Thomson SA;Lucas F;Solari R;House D;Begg M Eur J Pharmacol. 2013 Mar 15;704(1-3):49-57. doi: 10.1016/j.ejphar.2013.02.022. Epub 2013 Feb 27.
Loss of function mutations in the two key proteins which constitute Calcium-Release Activated Calcium (CRAC) channels demonstrate the critical role of this ion channel in immune cell function. The aim of this study was to demonstrate that inhibition of immune cell activation could be achieved with highly selective inhibitors of CRAC channels in vitro using cell preparations from human, rat, mouse and guinea-pig. Two selective small molecule blockers of CRAC channels; GSK-5498A and GSK-7975A were tested to demonstrate their ability to inhibit mediator release from mast cells, and pro-inflammatory cytokine release from T-cells in a variety of species. Both GSK-5498A and GSK-7975A completely inhibited calcium influx through CRAC channels. This led to inhibition of the release of mast cell mediators and T-cell cytokines from multiple human and rat preparations. Mast cells from guinea-pig and mouse preparations were not inhibited by GSK-5498A or GSK-7975A; however cytokine release was fully blocked from T-cells in a mouse preparation. GSK-5498A and GSK-7975A confirm the critical role of CRAC channels in human mast cell and T-cell function, and that inhibition can be achieved in vitro. The rat displays a similar pharmacology to human, promoting this species for future in vivo research with this series of molecules.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related Products


CAS 504-03-0 Nanofin

Nanofin
(CAS: 504-03-0)

Nanofin is neuropathic blocker used for mild to moderate hypertension.

CAS 922732-52-3 SSM 3 trifluoroacetate

SSM 3 trifluoroacetate
(CAS: 922732-52-3)

SSM 3 trifluoroacetate is a potent furin inhibitor (EC50 = 54 nM) which blocks furin-dependent cell surface processing of anthrax protective antigen-83 in vitro...

CAS 88898-17-3 Atrial natriuretic factor (1-28) (rat)

Atrial natriuretic factor (1-28) (rat)
(CAS: 88898-17-3)

Atrial natriuretic factor (1-28) (rat) is a 28 amino acid peptide corresponding to the rat protein sequence. It is an endogenous peptide synthesized in myoendoc...

Dirlotapide
(CAS: 481658-94-0)

Dirlotapide is a drug used to treat obesity in dogs works as a gut-selective microsomal triglyceride transfer protein (MTTP or MTP) inhibitor.

Ponatinib hydrochloride
(CAS: 1114544-31-8)

Ponatinib hydrochloride is an oral drug for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome–positive (Ph+) acute lymphoblastic leuke...

Sulofenur
(CAS: 10311-27-8)

Sulofenur is a diarylsulfonylurea with potential antineoplastic activity, whose antineoplastic mechanism of action is unknown.

Clamoxyquin Hydrochloride
(CAS: 4724-59-8)

Clamoxyquine, as the pamoate or hydrochloride salt, is an antiamebic and antidiarrheal drug used as a veterinary medicine to treat salmonids for infection with ...

CAS 55285-14-8 Carbosulfan

Carbosulfan
(CAS: 55285-14-8)

Carbosulfan is an organic compound adherent as a insecticide.

CAS 122341-38-2 Temoporfin

Temoporfin
(CAS: 122341-38-2)

Temoporfin, also known as m-THPC or KW-2345, is a synthetic light-activated chlorin with photodynamic activity. Upon systemic administration, temoporfin distri...

CAS 17560-51-9 Metolazone

Metolazone
(CAS: 17560-51-9)

Metolazone indirectly decreases the amount of water reabsorbed into the bloodstream by the kidney, which results in the decreases of blood volume and the increa...

CAS 329691-12-5 FPR A14

FPR A14
(CAS: 329691-12-5)

FPR A14 is a formyl peptide receptor (FPR) agonist that potently activates neutrophils in vitro (EC50 = 42 and 630 nM for neutrophil chemotaxis and Ca2+ mobiliz...

CAS 152751-57-0 Sevelamer HCl

Sevelamer HCl
(CAS: 152751-57-0)

Sevelamer HCl is a phosphate binding drug used to treat hyperphosphatemia via binding to dietary phosphate and prevents its absorption.

CAS 614-39-1 Procainamide Hydrochloride

Procainamide Hydrochloride
(CAS: 614-39-1)

Procainamide, a derivative of procaine with less CNS action., is an agent indicated for production of local or regional anesthesia and in the treatment of ventr...

CAS 58-60-6 Puromycin aminonucleoside

Puromycin aminonucleoside
(CAS: 58-60-6)

Puromycin aminonucleoside is the aminonucleoside portion of the antibiotic puromycin, which is a puromycin analog which does not inhibit protein synthesis or in...

CAS 332922-63-1 STOCK2S 26016

STOCK2S 26016
(CAS: 332922-63-1)

STOCK2S 26016 is a cell-permeable lysine deficient protein kinase (WNK) signaling inhibitor (IC50 = 16 μM). STOCK2S 26016 inhibits the binding of WNK1 and WNK4 ...

GYKI-20238
(CAS: 30725-74-7)

GYKI-20238 is a thiazolidine compound with anti-amnesic activity.

BAY-1142524

BAY-1142524 is a chymase inhibitor. Chymase is an enzyme that modulates the production of proteins playing a role in adverse cardiac tissue remodeling and fibro...

CC-17368
(CAS: 1547162-41-3)

CC-17368, a hydroxyisoindole derivative, is a metabolites of pomalidomide and has potential activity in anticancer study like multiple myeloma.

Brevianamide F
(CAS: 38136-70-8)

Brevianamide F, belongs to a class of naturally occurring 2,5-diketopiperazines, is produced by the fungi A.fumigates and Aspergillus sp.

CAS 554435-83-5 Deferasirox Fe3(addition) chelate

Deferasirox Fe3(addition) chelate
(CAS: 554435-83-5)

Deferasirox Fe3+ chelate is a rationally-designed oral iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long-term bl...

Quick Inquiry

Verification code

Featured Items