BMF-219
目录号 : GC25159BMF-219是一种高选择性和不可逆的menin抑制剂。
Cas No.:2448172-22-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment [1]: |
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Cell lines |
MOLM-13 cells |
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Preparation method |
Cells incubated with BMF-219 for 6 and 24 hours at 0.5 μM and 1 μM. |
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Reaction Conditions |
6 /24 hours; 0.5 /1 μM |
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Applications |
BMF-219 treatment significantly reduced MYC(v-myc avian myelocytomatosis viral oncogene homolog) transcription levels in cells. |
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Animal experiment [2]: |
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Animal models |
Zucker Diabetic Fatty (ZDF) rats |
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Preparation method |
Rats were dosed daily with BMF-219 or vehicle for 28 days and monitored for an additional 28 days post last dose. |
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Dosage form |
40-200mg/kg; 28days; p.o |
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Applications |
BMF-219 dose groups showed improved glycemic control by oral glucose tolerance test (OGTT) on day 25. |
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References: [1]. 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 [2]. 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 |
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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 /24 hours; 0.5 /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 /24 hours; 0.5 /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]。
| Cas No. | 2448172-22-1 | SDF | Download SDF |
| 分子式 | C31H34N8O3 | 分子量 | 566.65 |
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7648 mL | 8.8238 mL | 17.6476 mL |
| 5 mM | 0.353 mL | 1.7648 mL | 3.5295 mL |
| 10 mM | 0.1765 mL | 0.8824 mL | 1.7648 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Targeting the undruggable: menin inhibitors ante portas
J Cancer Res Clin Oncol 2023 Apr 27.PMID:37103568DOI:10.1007/s00432-023-04752-9
Acute myeloid leukaemias harbouring a rearrangement of the mixed lineage leukaemia gene (MLL) are aggressive haematopoietic malignancies that relapse early and have a poor prognosis (event-free survival less than 50%). Menin is a tumour suppressor, however, in MLL-rearranged leukaemias it functions as a co-factor which is mandatory for the leukaemic transformation by interaction with the N-terminal part of MLL, which is maintained in all MLL-fusion proteins. Inhibition of menin blocks leukaemogenesis and leads to differentiation and, in turn, to apoptosis of leukaemic blasts. Furthermore, nucleophosmin 1 (NPM1) binds to specific chromatin targets, which are co-occupied by MLL, and menin inhibition has been shown to trigger degradation of mNPM1 resulting in a rapid decrease in gene expression and activating histone modifications. Therefore, disruption of the menin-MLL axis blocks leukaemias driven by NPM1 mutations for which the expression of menin-MLL target genes (e.g., MEIS1, HOX etc.) is essential. To date at least six different menin-MLL inhibitors are undergoing clinical evaluation as first- and second-line monotherapy in acute leukaemias: DS-1594, BMF-219, JNJ-75276617, DSP-5336, revumenib, and ziftomenib, however, only for revumenib and ziftomenib early clinical data have been reported. In the revumenib phase I/II AUGMENT-101 trial (N = 68) with very heavily pretreated AML patients the ORR was 53% with a CR rate of 20%. The ORR in patients harbouring MLL rearrangement of mNPM1 was 59%. Patients who achieved a response had a mOS of 7 months. Similar results have been reported for ziftomenib in the phase I/II COMET-001 trial. ORR was 40% and CRc was 35% in AML patients with mNPM1. However, outcome was worse in AML patients with a MLL rearrangement (ORR 16.7%, CRc 11%). Differentiation syndrome was a notable adverse event. The clinical development of novel menin-MLL inhibitors is well in line with the currently ongoing paradigm shift towards targeted therapies seen in the AML treatment landscape. Moreover, the clinical assessment of combinations of these inhibitors with established therapy options in AML could be the fuel for an improved outcome of MLL/NPM1 patients.