5.32626

Ral Activation Inhibitor, BQU57

• Sinônimo(s): Ral Activation Inhibitor, BQU57, 6-Amino-1,3-dimethyl-4-(4-(trifluoromethyl)phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile, Ral Inhibitor, RalA Activation Inhibitor, RalB Activation Inhibitor
• Fórmula empírica (Notação de Hill): C₁₆H₁₃F₃N₄O
• Número CAS: 1637739-82-2
• Peso molecular: 334.30
• Número MDL: MFCD28902198
• Código UNSPSC: 12352200
• NACRES: NA.77

Propriedades

• Ensaio: ≥97% (HPLC)
• Nível de qualidade: 100
• Formulário: solid
• fabricante/nome comercial: Calbiochem^®
• condição de armazenamento: OK to freeze; protect from light
• cor: beige
• solubilidade: DMSO: 50 mg/mL
• temperatura de armazenamento: 2-8°C
• cadeia de caracteres SMILES: NC(OC1=C(C(C)=NN1C)C2C3=CC=C(C=C3)C(F)(F)F)=C2C#N
• InChI: 1S/C16H13F3N4O/c1-8-12-13(9-3-5-10(6-4-9)16(17,18)19)11(7-20)14(21)24-15(12)23(2)22-8/h3-6,13H,21H2,1-2H3
• chave InChI: IJCMHHSFXFMZAI-UHFFFAOYSA-N

Descrição

Descrição geral

A cell-permeable compound that specifically, reversibly, and stoichiometrically (1:1) binds to the GDP-bound Ral A/B in an allosteric manner (K_d = 7.7 µM) and blocks its activation.

A cell-permeable dihydropyranopyrazole compound that binds and locks RalA/B in the inactive GDP-bound form by targeting an allosteric site close to the guanine nucleotide-binding pocket (K_d = 7.7 µM binding study by ITC using RalB) in a 1:1 stoichiometric ratio, while exhibiting little affinity toward free or GTP-bound Ral. Shown to inhibit anchorage-independent growth of human lung cancer cell lines H358 & H2122 in vitro (IC₅₀ = 1.3 & 2.0 µM, respectively, in 2-4 wks by soft agar colony formation assays) by reducing cellular level of ATP-bound, active RalA/B (by >90% with 10 µM BQU57 treatment for 3 h; assessed by by RALBP1-agarose pull-down). BQU57 is bioavailable in mice via intraperitoneal injection (Plasma T_1/2 = 1.5 h, AUC_{0-5 h} = 28.6 µg·h/mL post single 50 mg/kg i.p. dosage) with overall tissue distribution, including brain (µg drug/g tissue = 4.1/liver, 2.4/kidney, 2.1/heart, 1.8/lung, 1.4/brain, 1.2/H2122 tumor; 3 h post single 50 mg/kg i.p. dosage). Shown to selectively downregulate leves of active RalA/B, but not Ras or RhoA, in H2122-derived tumor in mice in a dose-dependent manner (64% and 86% reduction of ATP-bound RalA and RalB, respectively, 3 h post single 50 mg/kg i.p. dosage) and effectively suppress H2122 tumor expansion when administered via daily i.p. dosing (by 70% 22 d post H2122 inoculation with 21 daily 50 mg/kg/d i.p. dosages) in vivo.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Ações bioquímicas/fisiológicas

Cell permeable: yes

Primary Target
Ral-GDP

Advertência

Toxicity: Standard Handling (A)

Reconstituição

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.

Outras notas

Yan, C., et al. 2014. Nature.515, 443.

Informações legais

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

Informações de segurança

• Código de classe de armazenamento: 11 - Combustible Solids
• Classe de risco de água (WGK): WGK 3
• Ponto de fulgor (°F): Not applicable
• Ponto de fulgor (°C): Not applicable