5.04297

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

• Synonym(e): RIP1 Inhibitor II, 7-Cl-O-Nec-1, 7-Cl-O-MH-Trp, Nec-1s, Nec-1 stable, RIPK1 Inhibitor II, Receptor-Interacting Protein 1 Inhibitor II, Necrosis Inhibitor IV, 5-((7-Chloro-1H-indol-3-yl)methyl)-3-methyl-2,4-imidazolidinedione, 5-((7-Chloro-1H-indol-3-yl)methyl)-3-methylimidazolidine-2,4-
• Empirische Formel (Hill-System): C₁₃H₁₂ClN₃O₂
• CAS-Nummer: 852391-15-2
• Molekulargewicht: 277.71
• UNSPSC-Code: 12352200
• NACRES: NA.77

Eigenschaften

• Assay: ≥95% (HPLC)
• Qualitätsniveau: 100
• Form: solid
• Hersteller/Markenname: Calbiochem^®
• Lagerbedingungen: OK to freeze; protect from light
• Farbe: off-white to pale yellow
• Löslichkeit: DMSO: 100 mg/mL
• Lagertemp.: 2-8°C
• InChI: 1S/C13H12ClN3O2/c1-17-12(18)10(16-13(17)19)5-7-6-15-11-8(7)3-2-4-9(11)14/h2-4,6,10,15H,5H2,1H3,(H,16,19)
• InChIKey: WIKGAEMMNQTUGL-UHFFFAOYSA-N

Beschreibung

Allgemeine Beschreibung

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 reduced in vitro and in vivo toxicity. 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 model in vivo (8 nmol/2 µL/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 µM with Nec-1), metabolic stability, as well as reduced in vitro and in vivo toxicity. 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 µM, 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 µL/mouse injections at 4 h & 6 h post occlusion) in a murine MCAO model in vivo.

Biochem./physiol. Wirkung

Cell permeable: yes

Primary Target
RIP1

Reversible: yes

Verpackung

Packaged under inert gas

Warnhinweis

Toxicity: Standard Handling (A)

Rekonstituierung

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.

Sonstige Hinweise

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.

Rechtliche Hinweise

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

Sicherheitshinweise

• Lagerklassenschlüssel: 11 - Combustible Solids
• WGK: WGK 3
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable