5.00505
CRM1 Inhibitor IV, KPT-251
Synonym(s):
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
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About This Item
Empirical Formula (Hill Notation):
C14H7F6N5O
CAS Number:
Molecular Weight:
375.23
UNSPSC Code:
12352200
Assay:
≥99% (HPLC)
Form:
solid
Storage condition:
OK to freeze, protect from light
assay
≥99% (HPLC)
Quality Segment
form
solid
manufacturer/tradename
Calbiochem®
storage condition
OK to freeze, protect from light
color
white
solubility
DMSO: 25 mg/mL
storage temp.
−20°C
General description
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 CRM1C528S-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 (tmax = 0.5 h; t1/2 = 3.83 h; Cmax = 439 ng/mL; AUCINF = 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 Actions
Cell permeable: yes
Primary Target
XPO1
XPO1
Reversible: no
Packaging
Packaged under inert gas
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Other Notes
Etchin, J., et al. 2013. Leukemia.27, 66.
Lapalombella, R., et al. 2012. Blood.120, 4621.
Lapalombella, R., et al. 2012. Blood.120, 4621.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)
Storage Class
11 - Combustible Solids
wgk
WGK 3
flash_point_f
Not applicable
flash_point_c
Not applicable
Certificates of Analysis (COA)
Search for Certificates of Analysis (COA) by entering the products Lot/Batch Number. Lot and Batch Numbers can be found on a product’s label following the words ‘Lot’ or ‘Batch’.
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