RIP1 Inhibitor II, 7-Cl-O-Nec-1-Calbiochem

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一般描述

A cell-permeable 7-chloroindolylmethyl-hydantoin that exhibits highly RIP1-selective inhibitory activity among >400 human kinases and is superior to its structural analog Necrostatin-1 (Cat. No. 480065) in blocking RIP1-dependent necroptosis due to improved potency (EC₅₀= 206 nM vs. 494 nM with Nec-1 for protecting FADD-deficient Jurkat from 30 h 10 ng/mL TNF-α-induced death), selectivity, metabolic stability, as well as reducedin vitroandin vivotoxicity. Reported to be blood-brain barrier permeable in mice and be efficacious in reducing brain infarct size when applied via intracerebroventricular injections in a murine MCAO modelin vivo(8 nmol/2 ?L/mouse).
A cell-permeable 7-chloroindolylmethyl-hydantoin that exhibits highly RIP1-selective inhibitory activity among >400 human kinases and is superior to its structural analog Necrostatin-1 (Cat. No. 480065) in blocking RIP1-dependent necroptosis due to improved potency (EC₅₀= 206 nM vs. 494 nM with Nec-1 for protecting FADD-deficient Jurkat from 30 h 10 ng/mL TNF-α-induced death), selectivity (no inhibition against IDO/indolamine 2,3-deoxygenase vs. IC₅₀= 11.4 ?M with Nec-1), metabolic stability, as well as reducedin vitroandin vivotoxicity. In addition, 7-Cl-O-Nec-1 is reported to exhibit blood-brain barrier permeability in mice (Brain and plasma conc. = 0.74 and 0.31 ?M, respectively, 30 min post 1 mg/6.25 mL/kg i.v. injection using male mice) and is efficacious in reducing brain infarct size when applied via intracerebroventricular injections (63% of control size 18 h post occlusion; two 8 nmol/2 ?L/mouse injections at 4 h & 6 h post occlusion) in a murine MCAO modelin vivo.

生化/生理作用

Cell permeable: yes
Reversible: yes
Primary Target
RIP1

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

重悬

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Use only fresh DMSO for reconstitution.

其他说明

Ofengeim, D., et al. 2015.Cell Reports10,In press.
Muller, A.J., et al. 2005.Nat. Med.11,312.
Degterev, A., et al. 2013.Nat. Chem. Biol.9,192.
Degterev, A., et al. 2013.Cell Death Differ.20,366.
Christofferson, D.E., et al. 2012.Cell Death Dis.3,e320.
Takahashi, N., et al. 2012.Cell Death Dis.3,e437.
Degterev, A., et al. 2008.Nat. Chem. Biol.4,313.
Degterev, A., et al. 2005.Nat. Chem. Biol.1,112.
Teng, X., et al. 2005.Bioorg. Med. Chem. Lett.15,5039.

法律信息

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

基本信息

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