Ziftomenib
(Synonyms: KO-539) 目录号 : GC64518
Ziftomenib是一种高选择性具口服活性的Menin-MLL（混合谱系白血病）相互作用抑制剂，用于治疗复发或难治性急性髓系白血病（AML）。
Cas No.:2134675-36-6
Sample solution is provided at 25 µL, 10mM.
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Ziftomenib is a highly selective and orally active inhibitor of the Menin-MLL (mixed lineage leukemia) interaction used to treat relapsed or refractory acute myeloid leukemia (AML)[1, 2]. Ziftomenib can inhibit the proliferation and survival of MLL-rearranged leukemia cells by blocking the binding of Menin protein to MLL fusion protein[3].
In vitro, Ziftomenib (150nM) treatment of AML cell lines (OCI-AML3, MOLM13, MV411 cells) induced transcriptional downregulation of MEIS1, PBX3, FLT3 and BCL2[4].
In vivo, oral treatment of AML cell xenograft mice with Ziftomenib (75mg/kg) significantly reduced the tumor burden in mice and prolonged the survival of mice[5].
References:
[1] Zhao J, Dong X, Che J. Ziftomenib (KO-539): a potent and selective Menin inhibitor for the treatment of recurrent or refractory acute myeloid leukemia[M]//Drug Discovery Stories. Elsevier, 2025: 455-466.
[2] Wang E S, Issa G C, Erba H P, et al. Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): A multicentre, open-label, multi-cohort, phase 1 trial[J]. The Lancet Oncology, 2024, 25(10): 1310-1324.
[3] Dhiman S, Dhillon V, Balasubramanian S K. Targeting Menin in Acute Myeloid Leukemia: Therapeutic Advances and Future Directions[J]. Cancers, 2024, 16(22): 3743.
[4] Rausch J, Dzama M M, Dolgikh N, et al. Menin inhibitor ziftomenib (KO-539) synergizes with drugs targeting chromatin regulation or apoptosis and sensitizes acute myeloid leukemia with MLL rearrangement or NPM1 mutation to venetoclax[J]. Haematologica, 2023, 108(10): 2837.
[5] Fiskus W, Daver N, Boettcher S, et al. Activity of menin inhibitor ziftomenib (KO-539) as monotherapy or in combinations against AML cells with MLL1 rearrangement or mutant NPM1[J]. Leukemia, 2022, 36(11): 2729-2733.
Ziftomenib是一种高选择性具口服活性的Menin-MLL（混合谱系白血病）相互作用抑制剂，用于治疗复发或难治性急性髓系白血病（AML）[1, 2]。Ziftomenib能够通过阻断Menin蛋白与MLL融合蛋白的结合，抑制MLL重排白血病细胞的增殖和存活[3]。
在体外，Ziftomenib（150nM）处理AML细胞系（OCI-AML3、MOLM13、MV411细胞），均诱导了MEIS1、PBX3、FLT3和BCL2的转录下调[4]。
在体内，Ziftomenib（75mg/kg）通过口服治疗AML细胞异种移植小鼠，显著降低了小鼠体内的肿瘤负荷，延长小鼠生存期[5]。
| Cell experiment [1]: | |
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Cell lines |
Acute myeloid leukemia (AML) cells (OCI-AML3, MOLM13 and MV411 cells) |
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Preparation Method |
OCI-AML3, MOLM13 and MV411 cells were incubated with 150nM Ziftomenib for 3-4 days, followed by RNA sequencing. |
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Reaction Conditions |
150nM; 3-4 days |
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Applications |
Ziftomenib uniformly induced transcriptional downregulation of MEIS1, PBX3, FLT3, and BCL2 in all NPM1mut (OCI-AML3 cells) and MLL-r cells (MOLM13 and MV411 cells) and demonstrated high consistency with the effects of other menin inhibitors. |
| Animal experiment [2]: | |
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Animal models |
NSG mice |
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Preparation Method |
NSG mice were engrafted with luciferized patient-derived MLL-AF9+FLT3-TKD expressing Acute myeloid leukemia (AML) cells and monitored for 5-7 days. Mice were imaged by Xenogen camera, randomized to equivalent bioluminescence and treated with vehicle, 75mg/kg of Ziftomenib (p.o., daily×5 days) and/or 30mg/kg of OTX015 (p.o., daily×5 days), or 30mg/kg of venetoclax (p.o., daily×5 days) for 2 weeks. Total bioluminescent flux was determined for each cohort by Xenogen camera. |
|
Dosage form |
75mg/kg; 5 days; p.o. |
|
Applications |
Whereas monotherapy with relatively low dose of venetoclax or OTX015 alone for 2 weeks Exhibited modest reduction of AML burden, treatment with Ziftomenib alone induced marked and significant reduction in AML burden. |
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References: |
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| Cas No. | 2134675-36-6 | SDF | Download SDF |
| 别名 | KO-539 | ||
| 分子式 | C33H42F3N9O2S2 | 分子量 | 717.87 |
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.393 mL | 6.965 mL | 13.9301 mL |
| 5 mM | 0.2786 mL | 1.393 mL | 2.786 mL |
| 10 mM | 0.1393 mL | 0.6965 mL | 1.393 mL |
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| 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 |
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| % 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。
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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