5.00505

CRM1 Inhibitor IV, KPT-251

• Synonym(e): CRM1 Inhibitor IV, KPT-251, KPT251, (Z)-2-(2-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)vinyl)-1,3,4-oxadiazole, Exportin 1 Inhibitor IV, Chromosome Region Maintenance 1 Protein Inhibitor IV, CRM1 Inhibitor IV, XPO1 Inhibitor IV
• Empirische Formel (Hill-System): C₁₄H₇F₆N₅O
• CAS-Nummer: 1388841-50-6
• Molekulargewicht: 375.23
• UNSPSC-Code: 12352200

Eigenschaften

• Assay: ≥99% (HPLC)
• Qualitätsniveau: 100
• Form: solid
• Hersteller/Markenname: Calbiochem^®
• Lagerbedingungen: OK to freeze; protect from light
• Farbe: white
• Löslichkeit: DMSO: 25 mg/mL
• Lagertemp.: −20°C

Beschreibung

Allgemeine Beschreibung

A cell-permeable, irreversible, triazole-containing heterotricyclic CRM1 inhibitor that effectively blocks CRM1-mediated nuclear export (4 h 1µM in U2OS cells) via covalent interaction with CRM1 NES- (nuclear export signal) binding groove cysteine (Cys528 in human). Exhibits antileukemic activity against primary human CD19⁺ CLL (IC₅₀<500 nM) via apoptosis induction even in the presence of stroma cells or other known CLL survival stimuli, while exhibiting little cytotoxicity toward CD56⁺ NK cells from healthy donors (1 µM; up to 72 h). Reported to prolong the survival of SCID mice (75 mg/kg p.o.) engrafted with murine Eμ-TCL1 or human MV4-11 leukemia in vivo.

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

A cell-permeable, irreversible, triazole-containing heterotricyclic CRM1 inhibitor that effectively blocks CRM1-mediated nuclear export (complete HIV-1 Rev nuclear retention after 4 h 1µM incubation in RevGFP-expressing U2OS cells) via covalent interaction with Cys528 (numbering based on human sequence) in the CRM1 NES- (nuclear export signal) binding groove, while being ineffective against CRM1^C528S-Rev interaction in RevBFP-expressing HeLa cells. Exhibits antileukemic activity in primary human CD19⁺ CLL (chronic lymphocytic leukemia) cultures (IC₅₀<500 nM) via apoptosis induction even in the presence of stroma cells or other known CLL survival stimuli, while exhibiting little cytotoxicity toward CD56⁺ NK cells from healthy donors (1 µM; up to 72 h). KPT-251 is orally available in mice (t_max = 0.5 h; t_1/2 = 3.83 h; C_max = 439 ng/mL; AUC_INF = 1590 h·ng/mL; 10 mg/kg p.o.) and reported to prolong the survival of SCID mice (75 mg/kg p.o.) engrafted with murine Eμ-TCL1 (mean survival time = 130.5 d vs. 72 d, respectively, with or without treatment) and human MV4-11 leukemia (62% survival rate on d 60 vs. 24% on d 34, respectively, with or without treatment) in vivo.

Biochem./physiol. Wirkung

Cell permeable: yes

Primary Target
XPO1

Reversible: no

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.

Sonstige Hinweise

Etchin, J., et al. 2013. Leukemia.27, 66.
Lapalombella, R., et al. 2012. Blood.120, 4621.

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