Eltanexor (KPT-8602, ONO-7706，ATG-016) is a second-generation, orally bioavailable XPO1 (also known as CRM1) inhibitor with IC50 values of 20−211\u2009nM in 10 AML lines after 3 days exposure.
Storage Temp
Store at -20°C
Shipped In
Ice chest + Ice pads
Grade
Moligand™
Action Type
INHIBITOR
Mechanism of action
Inhibitor of exportin 1
Product Description
Information
Eltanexor (KPT-8602) Eltanexor (KPT-8602, ONO-7706，ATG-016) is a second-generation, orally bioavailable XPO1 (also known as CRM1) inhibitor with IC50 values of 20−211 nM in 10 AML lines after 3 days exposure.
Targets
XPO1
In vitro
KPT-8602 is a potent inhibitor of AML cells in cell-based viability assays. KPT-8602 inhibits XPO1/cargo interactions and nuclear export, induces apoptosis of primary CLL cells and significantly inhibits proliferation of diffuse large B-cell lymphoma cell lines
In vivo
KPT-8602 is orally bioavailable and has similar pharmacokinetic properties to selinexor, but has markedly reduced (approximately 30-fold less) penetration across the blood−brain barrier. Toxicology studies in rats and monkeys indicate that KPT-8602 has a substantially better tolerability profile, probably due to its inability to penetrate into the CNS, with reduced anorexia, malaise and weight loss compared to selinexor. KPT-8602 exhibits superior anti-leukemic activity and better tolerability in the AML PDX models tested, with nearly complete elimination of human AML cells in the AML-CN model. KPT-8602 is minimally toxic to normal hematopoietic stem and progenitor cells. KPT-8602 does not accumulate in plasma after repetitive dosing and prolongs survival in a human leukemia xenograft model of AML.
1.Etchin J, Berezovskaya A, Conway AS, Galinsky IA, Stone RM, Baloglu E, Senapedis W, Landesman Y, Kauffman M, Shacham S et al.. (2017) KPT-8602, a second-generation inhibitor of XPO1-mediated nuclear export, is well tolerated and highly active against AML blasts and leukemia-initiating cells.. Leukemia, 31 (1):(143-150). [PMID:27211268][10.1021/op500134e]
2.Vercruysse T, De Bie J, Neggers JE, Jacquemyn M, Vanstreels E, Schmid-Burgk JL, Hornung V, Baloglu E, Landesman Y, Senapedis W et al.. (2017) The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity against Acute Lymphoblastic Leukemia.. Clin Cancer Res, 23 (10):(2528-2541). [PMID:27780859][10.1021/op500134e]
3.Hing ZA, Fung HY, Ranganathan P, Mitchell S, El-Gamal D, Woyach JA, Williams K, Goettl VM, Smith J, Yu X et al.. (2016) Next-generation XPO1 inhibitor shows improved efficacy and in vivo tolerability in hematological malignancies.. Leukemia, 30 (12):(2364-2372). [PMID:27323910][10.1021/op500134e]
Solution Calculators
Molarity Calculator
Determine the necessary mass, volume, or concentration for preparing a solution.
Dilution Calculator
Determine the dilution needed to prepare a stock solution.
K2303590