TAT-Gap19 - CAS 1507930-54-2
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C119H212N46O26
Molecular Weight:
2703.28
COA:
Inquire
Targets:
Others
Description:
TAT-Gap19 is a brain penetrating Cx43 hemichannel blocker (IC50 ~7 μM) with no significant affinity for gap junctions or Panx1 channels.
Brife Description:
Cx43 hemichannel blocker
Sequence:
Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Lys-Gln-Ile-Glu-Ile-Lys-Lys-Phe-Lys
MSDS:
Inquire
InChIKey:
ALNCFPIRTLVJPY-LJFAJSDSSA-N
InChI:
InChI=1S/C119H212N46O26/c1-5-67(3)93(111(188)160-78(34-14-20-56-124)100(177)152-77(33-13-19-55-123)106(183)163-88(65-69-28-8-7-9-29-69)110(187)162-87(113(190)191)35-15-21-57-125)165-109(186)86(48-51-92(170)171)161-112(189)94(68(4)6-2)164-108(185)85(47-50-90(128)168)159-99(176)76(32-12-18-54-122)151-101(178)79(37-23-59-142-115(131)132)154-103(180)81(39-25-61-144-117(135)136)155-104(181)82(40-26-62-145-118(137)138)157-107(184)84(46-49-89(127)167)158-105(182)83(41-27-63-146-119(139)140)156-102(179)80(38-24-60-143-116(133)134)153-98(175)75(31-11-17-53-121)150-97(174)74(30-10-16-52-120)149-96(173)73(36-22-58-141-114(129)130)148-91(169)66-147-95(172)72(126)64-70-42-44-71(166)45-43-70/h7-9,28-29,42-45,67-68,72-88,93-94,166H,5-6,10-27,30-41,46-66,120-126H2,1-4H3,(H2,127,167)(H2,128,168)(H,147,172)(H,148,169)(H,149,173)(H,150,174)(H,151,178)(H,152,177)(H,153,175)(H,154,180)(H,155,181)(H,156,179)(H,157,184)(H,158,182)(H,159,176)(H,160,188)(H,161,189)(H,162,187)(H,163,183)(H,164,185)(H,165,186)(H,170,171)(H,190,191)(H4,129,130,141)(H4,131,132,142)(H4,133,134,143)(H4,135,136,144)(H4,137,138,145)(H4,139,140,146)/t67-,68-,72-,73-,74-,75-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-,93-,94-/m0/s1
Canonical SMILES:
CCC(C)C(C(=O)NC(CCC(=O)O)C(=O)NC(C(C)CC)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CC1=CC=CC=C1)C(=O)NC(CCCCN)C(=O)O)NC(=O)C(CCC(=O)N)NC(=O)C(CCCCN)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCC(=O)N)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCCCN)NC(=O)C(CCCCN)NC(=O)C(CCCNC(=N)N)NC(=O)CNC(=O)C(CC2=CC=C(C=C2)O)N
1.Inhibition of connexin hemichannels alleviates non-alcoholic steatohepatitis in mice.
Willebrords J;Cogliati B;Pereira IVA;da Silva TC;Crespo Yanguas S;Maes M;Govoni VM;Lima A;Felisbino DA;Decrock E;Nogueira MS;de Castro IA;Leclercq I;Leybaert L;Rodrigues RM;Vinken M Sci Rep. 2017 Aug 15;7(1):8268. doi: 10.1038/s41598-017-08583-w.
While gap junctions mediate intercellular communication and support liver homeostasis, connexin hemichannels are preferentially opened by pathological stimuli, including inflammation and oxidative stress. The latter are essential features of non-alcoholic steatohepatitis. In this study, it was investigated whether connexin32 and connexin43 hemichannels play a role in non-alcoholic steatohepatitis. Mice were fed a choline-deficient high-fat diet or normal diet for 8 weeks. Thereafter, TAT-Gap24 or TAT-Gap19, specific inhibitors of hemichannels composed of connexin32 and connexin43, respectively, were administered for 2 weeks. Subsequently, histopathological examination was carried out and various indicators of inflammation, liver damage and oxidative stress were tested. In addition, whole transcriptome microarray analysis of liver tissue was performed. Channel specificity of TAT-Gap24 and TAT-Gap19 was examined in vitro by fluorescence recovery after photobleaching analysis and measurement of extracellular release of adenosine triphosphate. TAT-Gap24 and TAT-Gap19 were shown to be hemichannel-specific in cultured primary hepatocytes. Diet-fed animals treated with TAT-Gap24 or TAT-Gap19 displayed decreased amounts of liver lipids and inflammatory markers, and augmented levels of superoxide dismutase, which was supported by the microarray results.
2.Inhibition of astroglial connexin43 hemichannels with TAT-Gap19 exerts anticonvulsant effects in rodents.
Walrave L;Pierre A;Albertini G;Aourz N;De Bundel D;Van Eeckhaut A;Vinken M;Giaume C;Leybaert L;Smolders I Glia. 2018 Apr 23. doi: 10.1002/glia.23341. [Epub ahead of print]
Accumulating evidence shows a key function for astrocytic connexin43 (Cx43) signaling in epilepsy. However, the lack of experimental distinction between Cx43 gap junction channels (GJCs) and hemichannels (HCs) has impeded the identification of the exact contribution of either channel configurations to epilepsy. We therefore investigated whether TAT-Gap19, a Cx mimetic peptide that inhibits Cx43 HCs but not the corresponding Cx43 GJCs, influences experimentally induced seizures in rodents. Dye uptake experiments in acute hippocampal slices of mice demonstrated that astroglial Cx43 HCs open in response to the chemoconvulsant pilocarpine and this was inhibited by TAT-Gap19. In vivo, pilocarpine-induced seizures as well as the accompanying increase in D-serine microdialysate levels were suppressed by Cx43 HC inhibition. Moreover, the anticonvulsant action of TAT-Gap19 was reversed by exogenous D-serine administration, suggesting that Cx43 HC inhibition protects against seizures by lowering extracellular D-serine levels. The anticonvulsive properties of Cx43 HC inhibition were further confirmed in electrical seizure mouse models, i.e. an acute 6 Hertz (Hz) model of refractory seizures and a chronic 6 Hz corneal kindling model.
3.Connexin 43 Hemichannel as a Novel Mediator of Sterile and Infectious Inflammatory Diseases.
Li W;Bao G;Chen W;Qiang X;Zhu S;Wang S;He M;Ma G;Ochani M;Al-Abed Y;Yang H;Tracey KJ;Wang P;D'Angelo J;Wang H Sci Rep. 2018 Jan 9;8(1):166. doi: 10.1038/s41598-017-18452-1.
Cytoplasmic membrane-bound connexin 43 (Cx43) proteins oligomerize into hexameric channels (hemichannels) that can sometimes dock with hemichannels on adjacent cells to form gap junctional (GJ) channels. However, the possible role of Cx43 hemichannels in sterile and infectious inflammatory diseases has not been adequately defined due to the lack of selective interventions. Here we report that a proinflammatory mediator, the serum amyloid A (SAA), resembled bacterial endotoxin by stimulating macrophages to up-regulate Cx43 expression and double-stranded RNA-activated protein kinase R (PKR) phosphorylation in a TLR4-dependent fashion. Two well-known Cx43 mimetic peptides, the GAP26 and TAT-GAP19, divergently affected macrophage hemichannel activities in vitro, and differentially altered the outcome of lethal sepsis in vivo. By screening a panel of Cx43 mimetic peptides, we discovered that one cysteine-containing peptide, P5 (ENVCYD), effectively attenuated hemichannel activities, and significantly suppressed endotoxin-induced release of ATP and HMGB1 in vitro. In vivo, the P5 peptide conferred a significant protection against hepatic ischemia/reperfusion injury and lethal microbial infection.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related Products


CAS 464-49-3 D(+)-Camphor

D(+)-Camphor
(CAS: 464-49-3)

(R)-(+)-Camphor is a terpenoid used as a culinary flavouring agent in parts of asia.

Maleimide-PEG4-NHS
(CAS: 1286754-10-6)

This molecular is a sulfhydryl and amine reactive heterofuncational PEG linker. The chemical bonds that formed through Maleimide-PEG4-NHS linker are very stable...

CAS 1593478-56-8 (R)-CE3F4

(R)-CE3F4
(CAS: 1593478-56-8)

(R)-CE3F4 is an Epac inhibitor (IC50 = 4.2 and 44 μM for Epac1 and Epac2(B), respectively), suppressing the activation of Epac by cAMP.

CAS 61281-38-7 Schisandrin A

Schisandrin A
(CAS: 61281-38-7)

Schizandrin A is extracted from the seeds of Schisandra chinensis (Turcz.) Baill that is reported to have liver-protective, antitumor, and antioxidant activitie...

CAS 20283-92-5 Rosmarinic acid

Rosmarinic acid
(CAS: 20283-92-5)

Rosmarinic acid is a naturally occurring hydroxylated compound occured in many plants. Rosmarinic acid exhibits agonist activity at GPR35 and shows antiviral, a...

CAS 392721-37-8 Fasentin

Fasentin
(CAS: 392721-37-8)

Fasentin is a GLUT1 and GLUT4 inhibitor (IC50 = 68 μM). Fasentin sensitizes Fas receptor in a range of tumor cell lines (IC50 = 20 μM) via regulating the extrin...

AM-156 sodium
(CAS: 1175525-98-0)

AM-156 is a bio-active chemical and detailed information has not been published yet.

CAS 173352-39-1 Afobazole hydrochloride

Afobazole hydrochloride
(CAS: 173352-39-1)

Fabomotizole (brand name Afobazole) is an anxiolytic drug launched in Russia in the early 2000s. It produces anxiolytic and neuroprotective effects without any ...

Chemical Structure

CAS 1507930-54-2 TAT-Gap19

Quick Inquiry

Verification code

Featured Items