2024年9月12日 · JNJ-75276617 shows preclinical activity in KMT2A - or NPM1 -altered leukemia, synergizing with gilteritinib, venetoclax, and azacitidine. Antiproliferative activity in cells harboring menin mutations M327I and T349M is due to a unique binding mode.

In KMT2A-rearranged (KMT2A-r) and NPM1-mutant (NPM1c) acute myeloid leukemia (AML) cells, JNJ-75276617 inhibited the association of the menin-KMT2A complex with chromatin at target gene promoters, resulting in reduced expression of several menin-KMT2A target genes, including MEIS1 and FLT3.

2023年11月2日 · JNJ-75276617 is a potent and selective inhibitor of the interaction between the scaffolding protein menin and the methyltransferase KMT2A with preclinical activity in KMT2A-rearranged or NPM1-mutated leukemic cell lines and primary leukemia patient samples in vitro and in vivo (Kwon 2022).

2025年3月20日 · Bleximenib (also known as JNJ 75276617) is an orally administered menin-KMT2A (MLL1) inhibitor is being developed by Janssen Research & Development for the

Bleximenib是由Janssen Research & Development Llc研发的一种小分子药物，是一种Menin蛋白/组蛋白赖氨酸N-甲基转移酶MLL相互作用抑制剂。 目前该药物最高研发阶段为临床三期，用于治疗急性髓细胞样白血病。

Bleximenib, the novel menin-KMT2A inhibitor JNJ-75276617, impairs long-term proliferation and immune evasion in acute myeloid leukemia. (PubMed, Haematologica) - "Functionally, this results in enhanced sensitivity of leukemic blasts to T cell-mediated cytotoxicity in allogeneic and autologous settings.

The purpose of this study is to determine the recommended Phase 2 dose (s) (RP2D\ [s\]) of bleximenib in phase 1 (Part 1 \ [Dose Escalation\] and to determine the safety and tolerability at RP2D in Phase 1 Part 2 (Dose expansion). The purpose of the Phase 2 part of the study is to evaluate the efficacy of bleximenib at the RP2D.

Bleximenib, the novel menin-KMT2A inhibitor JNJ-75276617, impairs long-term proliferation and immune evasion in acute myeloid leukemia. (PubMed, Haematologica) Functionally, this results in enhanced sensitivity of leukemic blasts to T cell-mediated cytotoxicity in allogeneic and autologous settings.

2021年3月22日 · jnj-75276617 是一种口服生物可利用的、有效的、选择性的蛋白质-蛋白质相互作用抑制剂，可抑制组蛋白-赖氨酸 n-甲基转移酶 2a（[kmt2a]，也称为混合谱系白血病 1 [mll1]；野生型和融合型）之间的结合和 menin，在白血病细胞系和原发性白血病患者或具有 kmt2a 改变 ...

2024年9月12日 · JNJ-75276617 displayed potent antiproliferative activity across several AML and acute lymphoblastic leukemia (ALL) cell lines and patient samples harboring KMT2A or NPM1 alterations in vitro. In xenograft models of AML and ALL, JNJ-75276617 reduced leukemic burden and provided a significant dose-dependent survival benefit accompanied by ...