Cirtuvivint
(Synonyms: SM08502) 目录号 : GC63476
Cirtuvivint是一种口服有效的CDC样激酶（CLK）抑制剂，具有抗肿瘤活性。
Cas No.:2143917-62-6
Sample solution is provided at 25 µL, 10mM.
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Cirtuvivint is an orally bioavailable CDC-like kinase (CLK) inhibitor with anti-tumor activity[1, 2]. Cirtuvivint is a potent transcriptional regulator and splicing modulator, showing promise for the treatment of various advanced solid tumors[3]. Cirtuvivint inhibits Ewing sarcoma (ES) growth by suppressing EWS-FLI-1 expression and inducing alternative EWS-FLI1 splicing variants[4].
In vitro, treatment of SW480 cells with Cirtuvivint (0.03μM–3μM) for 48h induced apoptosis and significantly increased the levels of activated caspase 3/7[5].
In vivo, Cirtuvivint (12.5mg/kg) administered orally inhibited tumor growth in a mouse model of endometrial cancer, and its efficacy was enhanced when combined with paclitaxel[6]. Cirtuvivint (12.5, 25mg/kg) administered orally significantly inhibited tumor growth and induced tumor regression in a mouse model of ovarian cancer[7].
References:
[1] Govindharajulu J P, Dougherty K, Miner T, et al. Pharmacodynamics of venetoclax plus cirtuvivint a first-in-class splice variant regulator[J]. 2024.
[2] Teicher B A, Dexheimer T S, Silvers T, et al. RNA processing kinase inhibitors and epigenetic inhibitors in combination with oncology drugs or investigational agents in multi-cell type patient-derived tumor cell line spheroids[J]. Cancer Chemotherapy and Pharmacology, 2025, 95(1): 1-22.
[3] Dexheimer T S, Silvers T, Coussens N P, et al. Combinations of Cdc-like kinase (CLK) inhibitors with targeted oncology agents or standard chemotherapy in patient-derived multi-cell type tumor spheroids[J]. Cancer Research, 2024, 84(6_Supplement): 4608-4608.
[4] Vatolin S, Schwartz G K. Cirtuvivint inhibits Ewing sarcoma (ES) growth by suppressing EWS-FLI-1 expression and inducing alternate EWS-FLI1 splice variants[J]. Cancer Research, 2025, 85(8_Supplement_1): 4272-4272.
[5] Tam B Y, Chiu K, Chung H, et al. The CLK inhibitor SM08502 induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models[J]. Cancer letters, 2020, 473: 186-197.
[6] Corr B R, Moroney M R, Woodruff E, et al. Combination CDC-like kinase inhibition (CLK)/Dual-specificity tyrosine-regulated kinase (DYRK) and taxane therapy in CTNNB1-mutated endometrial cancer[J]. bioRxiv, 2023.
[7] Chung H, Sitts L, Creger E, et al. Abstract A09: SM08502, a novel, small-molecule CDC-like kinase (CLK) inhibitor, demonstrates strong inhibition of the Wnt signaling pathway and antitumor effects in diverse ovarian cancer models[J]. Clinical Cancer Research, 2020, 26(13_Supplement): A09-A09.
Cirtuvivint是一种口服有效的CDC样激酶（CLK）抑制剂，具有抗肿瘤活性[1, 2]。Cirtuvivint是一种强效的转录调节和剪接修饰剂，能够用于治疗多种晚期实体瘤[3]。Cirtuvivint能够通过抑制 EWS-FLI-1表达和诱导替代EWS-FLI1剪接变体来抑制Ewing肉瘤（ES）生长[4]。
在体外，Cirtuvivint（0.03μM-3μM）处理SW480细胞48h，诱导了细胞凋亡，显著升高了细胞内激活的caspase 3/7水平[5]。
在体内，Cirtuvivint（12.5mg/kg）通过口服治疗子宫内膜癌模型小鼠，抑制了肿瘤的生长，Cirtuvivint与紫杉醇联合使用的疗效更好[6]。Cirtuvivint（12.5, 25mg/kg）通过口服治疗卵巢癌模型小鼠，显著抑制了肿瘤生长，引起了肿瘤消退[7]。
| Cell experiment [1]: | |
Cell lines | SW480 cells |
Preparation Method | SW480 cells (7500 cells/well) were incubated overnight, then treated with DMSO, Cirtuvivint (5 doses, range 0.03μM-3μM), or staurosporine (0.1μM) at 37°C for 48h. Cells were then incubated with CellEvent™ caspase 3/7 green detection reagent at 37°C for 30min, followed by Hoechst 33342 (blue) dye. Quantification of apoptotic (green-labeled) and total (blue-labeled nuclei) cells per well was performed on a CellInsight™ CX5 imager for all wells of three replicate plates, and the ratio of green:blue cells was calculated and expressed as a percentage; the result was the average of the triplicate wells. |
Reaction Conditions | 0.03μM-3μM; 48h |
Applications | Cirtuvivint induced cell apoptosis. Treatment of SW480 cells with Cirtuvivint resulted in increased levels of activated caspase 3/7. |
| Animal experiment [2]: | |
Animal models | Athymic nude mice (Charles River Labs, Strain 553) |
Preparation Method | Mice were subcutaneously injected with 5×106 HEC265, Ishikawa, or Ishikawa-S33Y cells, or 1×107 HEC265 or SNGM cells on the right flank. Tumor progression was measured using calipers every 2 days, and tumor volume as well as % change in tumor volume were recorded. Once a tumor in each flank population grew to over 100mm3, treatment was initiated in all mice. For all experiments, mice were treated with paclitaxel alone (10mg/kg weekly, i.p.), Cirtuvivint alone (12.5mg/kg, daily, p.o.), paclitaxel+Cirtuvivint, or vehicle. Body weight was measured twice per week during treatment as a surrogate for toxicity. Body weight loss of >10% was considered indicative of severe reaction to treatment. The mice were sacrificed, and the tumors were surgically resected and weighed. Tumor burden was calculated based on the weight of resected tumors. Blood samples were collected at time of death via cardiac punction for complete blood count (CBC) and blood chemistry analysis (AST, ALT, and ALP), blood volume permitting. |
Dosage form | 12.5mg/kg/day; p.o. |
Applications | The efficacy of Cirtuvivint alone is comparable to that of paclitaxel alone. The combination therapy of Cirtuvivint and paclitaxel is more effective than either drug used alone. |
References: | |
| Cas No. | 2143917-62-6 | SDF | |
| 别名 | SM08502 | ||
| 分子式 | C24H25N7O | 分子量 | 427.5 |
| 溶解度 | DMSO : 12.5 mg/mL (29.24 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | 4°C, away from moisture and 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 | 2.3392 mL | 11.6959 mL | 23.3918 mL |
| 5 mM | 467.8 μL | 2.3392 mL | 4.6784 mL |
| 10 mM | 233.9 μL | 1.1696 mL | 2.3392 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 | ||||||||||
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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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- Purity: >98.00%
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