CFI-402257
目录号 : GC18491
CFI-402257 是 Mps1 的选择性抑制剂，CFI-402257 抑制 Mps1 的 IC50 值为 1.2 ± 0.4 nM，与 ATP 竞争，Ki 值为 0.09 ± 0.02 nM，具有高特异性、选择性和效力 [2,7]。
Cas No.:1610759-22-2
Sample solution is provided at 25 µL, 10mM.
CFI-402257 is a selective inhibitor of Mps1, CFI-402257 inhibited Mps1 with an IC50 value of 1.2 ± 0.4 nM, and was ATP competitive with a Ki value of 0.09 ± 0.02 nM, It has high specificity, selectivity and potency [2,7].
CFI-402257 induces senescence-like responses and SASP secretion in HCC[1]. CFI-402257 suppresses MM(Malignant mesothelioma) growth. Mps-1 is overexpressed in MM and that its expression correlates with poor patients' outcome. In vitro, CFI-402257-mediated inhibition of Mps-1 resulted in abrogation of the mitotic checkpoint, premature progression through mitosis, marked aneuploidy and mitotic catastrophe[3]. CFI-402257, significantly inhibited GBM cell proliferation and improved the growth-suppressive effect of TMZ[4]. When evaluated the cellular effects of the potent clinical TTKi CFI-402257 in TNBC models. CFI-402257 induced apoptosis and potentiated aneuploidy in TNBC lines by accelerating progression through mitosis and inducing mitotic segregation errors[6].
In BALB/cAnN - nu mice, TTK inhibition by CFI-402257 shrank HCC tumors and reduced lung metastasis[1]. Oral QD of CMI-402257 showed dose-dependent activity in mice with established tumors in xenografts of MDA-MB-231 human TNBC cells[2]. Developed a panel of CDK4/6i-resistant breast cancer cell lines and patient-derived organoids, TTK inhibitor CFI-402257 as a therapeutic strategy for a defined subset of ER+ breast cancer patients who develop resistance to CDK4/6i[6].
References:
[1]: Chan CY, Chiu DK, et,al. CFI-402257, a TTK inhibitor, effectively suppresses hepatocellular carcinoma. Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2119514119. doi: 10.1073/pnas.2119514119. Epub 2022 Aug 1. PMID: 35914158; PMCID: PMC9371652.
[2]: Mason JM, Wei X, et,al. Functional characterization of CFI-402257, a potent and selective Mps1/TTK kinase inhibitor, for the treatment of cancer. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3127-3132. doi: 10.1073/pnas.1700234114. Epub 2017 Mar 7. PMID: 28270606; PMCID: PMC5373378.
[3]: Szymiczek A, Carbone M, et,al. Inhibition of the spindle assembly checkpoint kinase Mps-1 as a novel therapeutic strategy in malignant mesothelioma. Oncogene. 2017 Nov 16;36(46):6501-6507. doi: 10.1038/onc.2017.266. Epub 2017 Jul 31. PMID: 28759042; PMCID: PMC5690838.
[4]: Yu J, Gao G, et,al.TTK Protein Kinase promotes temozolomide resistance through inducing autophagy in glioblastoma. BMC Cancer. 2022 Jul 18;22(1):786. doi: 10.1186/s12885-022-09899-1. PMID: 35850753; PMCID: PMC9290216.
[5]: Thu KL, Silvester J, et,al.Disruption of the anaphase-promoting complex confers resistance to TTK inhibitors in triple-negative breast cancer. Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):E1570-E1577. doi: 10.1073/pnas.1719577115. Epub 2018 Jan 29. PMID: 29378962; PMCID: PMC5816201.
[6]: Soria-Bretones I, Thu KL, et,al.The spindle assembly checkpoint is a therapeutic vulnerability of CDK4/6 inhibitor-resistant ER+ breast cancer with mitotic aberrations. Sci Adv. 2022 Sep 9;8(36):eabq4293. doi: 10.1126/sciadv.abq4293. Epub 2022 Sep 7. PMID: 36070391; PMCID: PMC9451148.
[7]: Laufer R, Li SW, et,al. Discovery of 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides as novel, highly potent and selective, orally bioavailable inhibitors of Tyrosine Threonine Kinase, TTK. Bioorg Med Chem Lett. 2016 Aug 1;26(15):3562-6. doi: 10.1016/j.bmcl.2016.06.021. Epub 2016 Jun 9. PMID: 27335255.
CFI-402257 是 Mps1 的选择性抑制剂，CFI-402257 抑制 Mps1 的 IC50 值为 1.2 ± 0.4 nM，与 ATP 竞争，Ki 值为 0.09 ± 0.02 nM，具有高特异性、选择性和效力 [2,7]。
CFI-402257 在 HCC 中诱导衰老样反应和 SASP 分泌[1]。 CFI-402257 抑制 MM（恶性间皮瘤）的生长。 Mps-1 在 MM 中过表达，其表达与贫困患者相关结果。在体外，CFI-402257 介导的 Mps-1 抑制导致有丝分裂检查点的废除、有丝分裂过早进展、显着的非整倍体和有丝分裂灾难[3]。 CFI-402257，显着抑制 GBM 细胞增殖并改善 TMZ[4] 的生长抑制作用。当评估有效的临床 TTKi CFI-402257 在 TNBC 模型中的细胞效应时。 CFI-402257 通过加速有丝分裂进展和诱导有丝分裂分离错误，在 TNBC 细胞系中诱导细胞凋亡和增强非整倍体[6]。
在 BALB/cAnN - nu 小鼠中，CFI-402257 抑制 TTK 可缩小 HCC 肿瘤和减少肺转移[1]。 CMI-402257 的口服 QD 在 MDA-MB-231 人 TNBC 细胞异种移植物中已建立肿瘤的小鼠中表现出剂量依赖性活性[2]。开发了一组 CDK4/6i 抗性乳腺癌细胞系和患者来源的类器官，TTK 抑制剂 CFI-402257 作为对 CDK4/6i 产生抗性的特定 ER+ 乳腺癌患者亚群的治疗策略[6]。
| Kinase experiment [1]: | |
|
Preparation Method |
HCT116 cells transfected with full-length human Mps1 were treated with nocodazole for 17 hours and pretreated with MG132 for 30 minutes, followed by treatment with CFI-402257 or DMSO for 4 hours to target phospho-MPS1 (T12/S15) and Mps1,The lysates were analyzed by Western blot analysis |
|
Reaction Conditions |
1-400nM CFI-402257 for 4h |
|
Applications |
CFI-402257 inhibited Mps1 with an IC50 value of 1.2 ± 0.4 nM, and was ATP competitive with a Ki value of 0.09 ± 0.02 nM. |
| Cell experiment [2]: | |
|
Cell lines |
MHCC97L cells |
|
Preparation Method |
MHCC97L cells were treated with different concentrations of CFI-402257 for 48 h and stained with DAPI for DNA staining. |
|
Reaction Conditions |
1/2.5uM Stattic for 24 or 48 h |
|
Applications |
Micronucleus formation in human HCC cells treated with CFI-402257, Treatment with CMI-402257 increased DNA damage. |
| Animal experiment [3]: | |
|
Animal models |
BALB/cAnN - nu mice |
|
Preparation Method |
BALB/cAnN-nu mice were orthotopically implanted with luciferase-labeled MHCC97L cells for 2 wk and were administered with vehicle control (Ctrl) or 6 mg/kg/day CFI-402257 for 19 d. |
|
Dosage form |
6 mg/kg/day CFI-402257 for 19 d |
|
Applications |
TTK inhibition by CFI-402257 shrank HCC tumors and reduced lung metastasis. |
|
References: [1]. Mason JM, Wei X, et,al. Functional characterization of CFI-402257, a potent and selective Mps1/TTK kinase inhibitor, for the treatment of cancer. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3127-3132. doi: 10.1073/pnas.1700234114. Epub 2017 Mar 7. PMID: 28270606; PMCID: PMC5373378. [2]. Chan CY, Chiu DK, et,al. CFI-402257, a TTK inhibitor, effectively suppresses hepatocellular carcinoma. Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2119514119. doi: 10.1073/pnas.2119514119. Epub 2022 Aug 1. PMID: 35914158; PMCID: PMC9371652. |
|
| Cas No. | 1610759-22-2 | SDF | |
| 化学名 | N-cyclopropyl-4-[7-[[(cis-3-hydroxy-3-methylcyclobutyl)methyl]amino]-5-(3-pyridinyloxy)pyrazolo[1,5-a]pyrimidin-3-yl]-2-methyl-benzamide | ||
| Canonical SMILES | CC1=C(C(NC2CC2)=O)C=CC(C3=C4N=C(OC5=CN=CC=C5)C=C(NC[C@@H]6C[C@@](O)(C)C6)N4N=C3)=C1 | ||
| 分子式 | C28H30N6O3 | 分子量 | 498.6 |
| 溶解度 | DMSO : ≥ 125 mg/mL (233.63 mM) | 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。 |
||
| 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 | 2.0056 mL | 10.0281 mL | 20.0562 mL |
| 5 mM | 0.4011 mL | 2.0056 mL | 4.0112 mL |
| 10 mM | 0.2006 mL | 1.0028 mL | 2.0056 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。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
