2022年10月1日 · Since the newer XPO1 inhibitor eltanexor (elta) is given 5 days/week in early-phase clinical studies, we compared the antileukemic effects of intermittent (2d/w) and prolonged (5d/w) XPO1 inhibition in NPM1c AML models.

In this study, we evaluated whether inhibition of SIK3 with the tool compound YKL-05-099 can suppress MEF2C function and attenuate disease progression in animal models of AML. Genetic targeting of SIK3 or MEF2C selectively suppressed the growth of transformed hematopoietic cells under in vitro and in vivo conditions.

XPO1 inhibition by selinexor (seli) leads to NPM1c nuclear relocalization, loss of HOX expression, and terminal differentiation. However, 2 days/week seli did not result in evident benefit for NPM1c AML patients. We hypothesize that prolonged XPO1 inhibition is necessary to achieve optimal antileukemic activity.

2022年10月1日 · Poster: AML-099 Prolonged XPO1 Inhibition Is Essential for Optimal Anti-Leukemic Activity in NPM1-Mutated AML October 2022 Clinical Lymphoma, Myeloma and Leukemia 22:S128

2019年11月13日 · Our previous CRISPR screens in AML cell lines identified Salt-Inducible Kinase 3 (SIK3) as an essential gene for a subset of AML cells with high expression of the oncogenic transcription factor MEF2C, such as AMLs harboring …

2022年10月1日 · XPO1 inhibition by selinexor (seli) leads to NPM1c nuclear relocalization, loss of HOX expression, and terminal differentiation. However, 2 days/week seli did not result in evident benefit for NPM1c AML patients. We hypothesize that prolonged XPO1 inhibition is necessary to achieve optimal antileukemic activity.

2020年1月2日 · In this study, we evaluated whether inhibition of SIK3 with the tool compound YKL-05-099 can suppress MEF2C function and attenuate disease progression in animal models of AML. Genetic targeting of SIK3 or MEF2C selectively suppressed the growth of transformed hematopoietic cells under in vitro and in vivo conditions.

AML-099 Prolonged XPO1 Inhibition Is Essential for Optimal Anti-Leukemic Activity in NPM1-Mutated AML

Context: RARA-positive AML is a novel, genomically defi ned subset with an actionable target for treatment with tamibarotene, an oral and selective RAR agonist (McKeown 2017). In a previous trial in RARA-positive newly diagnosed (ND) AML patients ineligible for standard induction therapy, tamibarotene/azacitidine

ykl-05-099是一种化学合成的sik抑制剂，主要抑制sik1和 中心点： AML细胞在体内外对盐诱导的激酶3的遗传或化学抑制均具有独特的敏感性。