BMF-219 is a highly selective and irreversible inhibitor of menin which has shown very promising activity in in-vitro and in-vivo preclinical tumour models[1-3].
BMF-219(6 or 24 hours; 0.5 or 1 µM) treatment significantly reduced MYC(v-myc avian myelocytomatosis viral oncogene homolog) transcription levels in cells[4].
BMF-219(40-200mg/kg; 28days; p.o) significantly reduces HbA1c and controls blood glucose levels in a 4-week dosing study in ZDF rats. BMF-219 significantly reduces blood lipemic levels and body weight in Streptozotocin (STZ) rats[5-6]. A comprehensive panel of Chronic Lymphocytic Leukemia (CLL) samples isolated from patients with Rai Stage 1 to 3 disease were cultured ex vivo in the presence of BMF-219 to assess the antileukemic activity. BMF-219 demonstrated high potency, achieving > 98% cell lethality at 1 µM exposure with IC50 values in the range of 0.1 to 0.38 µM[7].
References:
[1]. Dempke WCM, Desole M, et. al. Targeting the undruggable: menin inhibitors ante portas. J Cancer Res Clin Oncol. 2023 Sep;149(11):9451-9459. doi: 10.1007/s00432-023-04752-9. Epub 2023 Apr 27. PMID: 37103568.
[2]. Farhad Ravandi et al., COVALENT-101: A phase 1 study of BMF-219, a novel oral irreversible menin inhibitor, in patients with relapsed/refractory (R/R) acute leukemia (AL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM). JCO 40, TPS7064-TPS7064(2022). DOI:10.1200/JCO.2022.40.16_suppl.TPS7064
[3]. JOSE E. RODRIGUEZ, et. al. 91-LB: COVALENT-111, a Phase 1/2 Trial of BMF-219, a Covalent Menin Inhibitor, in Patients with Type 2 Diabetes Mellitus—Preliminary Results. Diabetes 20 June 2023; 72 (Supplement_1): 91-LB. https://doi.org/10.2337/db23-91-LB
[4]. Priyanka Somanath, Daniel Lu,et. al. Novel Irreversible Menin Inhibitor, BMF-219, Shows Potent Single Agent Activity in Clinically Relevant DLBCL Cells. DOI: 10.1182/blood-2021-148045
[5]. PRIYANKA SOMANATH, et. al. 113-LB: Oral Menin Inhibitor, BMF-219, Displays a Significant and Durable Reduction in HbA1c in a Type 2 Diabetes Mellitus Rat Model. Diabetes 1 June 2022; 71 (Supplement_1): 113-LB. https://doi.org/10.2337/db22-113-LB
[6]. THOMAS BUTLER, et. al. 851-P: Oral Long-Acting Menin Inhibitor Normalizes Type 2 Diabetes Mellitus (T2DM) in Two Rat Models. Diabetes 1 June 2022; 71 (Supplement_1): 851-P. https://doi.org/10.2337/db22-851-P
[7]. Priyanka Somanath et al., Preclinical activity of irreversible Menin inhibitor, BMF-219, in chronic lymphocytic leukemia. JCO 40, 7541-7541(2022). DOI:10.1200/JCO.2022.40.16_suppl.7541
BMF-219是一种高选择性和不可逆的menin抑制剂,在小鼠模型中具有良好的抑制效果 [1-3]。
BMF-219(6 or 24 hours; 0.5 or 1 µM)治疗显著降低了细胞中MYC的转录水平[4]。
BMF-219(40-200mg/kg; 28days; p.o) 在为期4周的ZDF大鼠剂量研究中,显著降低HbA1c并控制血糖水平。BMF-219可显著降低链脲佐菌素(STZ)大鼠的血脂水平和体重[5-6]。从Rai 1至3期患者中分离的慢性淋巴细胞白血病(CLL)样本在体外存在BMF-219下培养,以评估其抗白血病活性。BMF-219表现出很高的效力,在1µM暴露下达到> 98%的细胞致死率,IC50值在0.1至0.38µM范围内[7]。