Selinexor

KPT-330, analog of KPT-185, is an orally bioavailable selective CRM1 inhibitor.IC50 value: Target: CRM1in vitro: As the clinical candidate analog of KPT-185, KPT-330 exhibits similar effects on the viability of T-ALL cells and elicits rapid apoptotic response. KPT-330 also reduces cell growth in MOLT-4, Jurkat, HBP-ALL, KOPTK-1, SKW-3, and DND-41 cell lines, with IC50 values of 34-203 nM [1]. in vivo: KPT-330 dramatically suppresses the growth of T-ALL cells (MOLT-4) and AML cells (MV4–1
Selinexor is a first-in-class selective inhibitor of nuclear transport (SINE) compound. It is currently approved for the treatment of multiple myeloma, a cancer which forms from antibody-producing plasma cells. This condition is typically treated with high dose [bortezomib] and dexamethasone chemotherapy followed by autologous stem-cell transplant. Other chemotherapies for multiple myeloma include [lenalidomide] and [dexamethasone], [thalidomide], and may include [melphalan] if the patient is not eligible for transplant. Selinexor was approved by the FDA in June 2019. It was granted fast track and orphan designation as well as accelerated approval based on single arm, open label trial data. The Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma (BOSTON) trial is planned to finish in 2020.|Selinexor is an orally available, small molecule inhibitor of CRM1 (chromosome region maintenance 1 protein, exportin 1 or XPO1), with potential antineoplastic activity. Selinexor modifies the essential CRM1-cargo binding residue cysteine-528, thereby irreversibly inactivates CRM1-mediated nuclear export of cargo proteins such as tumor suppressor proteins (TSPs), including p53, p21, BRCA1/2, pRB, FOXO, and other growth regulatory proteins. As a result, this agent, via the approach of selective inhibition of nuclear export (SINE), restores endogenous tumor suppressing processes to selectively eliminate tumor cells while sparing normal cells. CRM1, the major export factor for proteins from the nucleus to the cytoplasm, is overexpressed in a variety of cancer cell types.