CTX-712
目录号 : GC65023
CTX-712是一种强效的cdc2相似激酶（CLK）抑制剂，IC50值为1.4nM。
Cas No.:2144751-78-8
Sample solution is provided at 25 µL, 10mM.
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CTX-712 is a potent CDC2 like kinase (CLK) inhibitor with an IC50 value of 1.4nM [1]. CLK is associated with various neurodegenerative diseases, metabolic regulation, and viral infections [2]. CTX-712 can inhibit cancer survival and the growth of cancer cells [3].
In vitro, after 6 hours of treatment with CTX-712 on MOLM13 cells, the phosphorylation levels of SRSF2, SRSF4, and SRSF6 in the cells decreased in a dose-dependent manner, and apoptosis was induced. 72 hours of CTX-712 treatment inhibited the proliferation of acute myeloid leukemia cell lines (U937, THP1, MOLM13), with IC50 values of 71.3±12.5nM, 147±16.1nM, and 35.5±2.3nM, respectively [4]. CTX-712 also inhibited the proliferation of human myeloid K562 and MV-4-11 cells, with IC50 values of 0.15μM and 0.036μM, respectively. The IC50 value of CTX-712 for primary acute myeloid leukemia (AML) cells was 0.078μM, indicating its anti-leukemia effect [3].
In vivo, oral administration of CTX-712 (6.25-12.5mg/kg/day) for 2 weeks inhibited t inhibits tumor size in mice with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), and improves survival rate [3].
References:
[1] Tang J, Xie Y, Huang J, et al. A critical update on the strategies towards small molecule inhibitors targeting Serine/arginine-rich (SR) proteins and Serine/arginine-rich proteins related kinases in alternative splicing. Bioorg Med Chem. 2022;70:116921.
[2] Qin Z, Qin L, Feng X, Li Z, Bian J. Development of Cdc2-like Kinase 2 Inhibitors: Achievements and Future Directions. J Med Chem. 2021 Sep 23;64(18):13191-13211.
[3] Yoda A, Morishita D, Mizutani A, et al. CTX-712, a Novel Clk inhibitor targeting myeloid neoplasms with SRSF2 mutation[J]. Blood, 2019, 134: 404.
[4] Yang H, Fang Z, Wei Y, et al. CDC2-like Kinases (CLKs) Inhibition As a Novel Targeted Therapeutic Strategy in Myelodysplastic Syndromes (MDS)[J]. Blood, 2024, 144: 6691.
CTX-712是一种强效的cdc2相似激酶（CLK）抑制剂，IC50值为1.4nM [1]。CLK与多种神经退行性疾病、代谢调节以及病毒感染有关 [2]。CTX-712能够抑制癌细胞的存活和生长 [3]。
在体外实验中，CTX-712处理MOLM13细胞6小时后，细胞SRSF2、SRSF4和SRSF6的磷酸化水平呈剂量依赖性下降，并且诱导了凋亡。72小时的CTX-712处理抑制了急性髓系白血病细胞系（U937、THP1、MOLM13）的增殖，其IC50值分别为71.3±12.5nM、147±16.1nM和35.5±2.3nM [4]。CTX-712对人类髓系K562和MV-4-11细胞的增殖也有抑制作用，其IC50值分别为0.15μM和0.036μM。CTX-712对原发性急性髓系白血病（AML）细胞的IC50值为0.078μM，表明其具有抗白血病作用 [3]。
在体内实验中，口服给予CTX-712（6.25-12.5mg/kg/d）2周，能够抑制患有骨髓增生异常综合征（MDS）和急性髓系白血病（AML）的小鼠的肿瘤大小，并提高生存率 [3]。
| Animal experiment [1]: | |
Animal models | AML/MDS model mice |
Preparation Method | Established 13 xenograft tumor (PDX) models derived from cells of myelodysplastic syndrome/acute myeloid leukemia. Further investigated the effect of CTX-712 on tumor growth in vivo, and administered different doses of CTX-712 (6.25, 12.5mg/kg/day) to them. After two weeks of treatment, the tumor volume (in cubic millimeters) was measured, along with the survival rate of the mice. |
Dosage form | 6.25, 12.5mg/kg/day for 2 weeks; oral |
Applications | Among the 5 mice treated with the high-dose regimen (12.5mg/kg), 4 achieved complete remission (the tumors completely shrank to an undetectable size). Two weeks after treatment with CTX-712, the tumor volume of the SRSF2 P95L mutant model mice significantly decreased, and CTX-712 also significantly increased the survival rate of the SRSF2 P95L model mice. |
References: | |
| Cas No. | 2144751-78-8 | SDF | Download SDF |
| 分子式 | C19H17FN8O2 | 分子量 | 408.39 |
| 溶解度 | 储存条件 | Store at -20°C,protect from light | |
| 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 | 2.4486 mL | 12.2432 mL | 24.4864 mL |
| 5 mM | 0.4897 mL | 2.4486 mL | 4.8973 mL |
| 10 mM | 0.2449 mL | 1.2243 mL | 2.4486 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。
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- Purity: >98.50%
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