5.32626

Ral Activation Inhibitor, BQU57

• Synonym(e): 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
• Empirische Formel (Hill-System): C₁₆H₁₃F₃N₄O
• CAS-Nummer: 1637739-82-2
• Molekulargewicht: 334.30
• MDL-Nummer: MFCD28902198
• UNSPSC-Code: 12352200
• NACRES: NA.77

Eigenschaften

• Assay: ≥97% (HPLC)
• Qualitätsniveau: 100
• Form: solid
• Hersteller/Markenname: Calbiochem^®
• Lagerbedingungen: OK to freeze; protect from light
• Farbe: beige
• Löslichkeit: DMSO: 50 mg/mL
• Lagertemp.: 2-8°C
• SMILES String: NC(OC1=C(C(C)=NN1C)C2C3=CC=C(C=C3)C(F)(F)F)=C2C#N

Beschreibung

Allgemeine Beschreibung

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.

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.

Biochem./physiol. Wirkung

Cell permeable: yes

Primary Target
Ral-GDP

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

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

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