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COTI-2

CAS No. : 1039455-84-9

MCE 国际站：COTI-2

产品活性：COTI-2，一种具有口服活性的，低毒的抗癌活性分子，是一种第三代 p53 突变体 (p53 mutant) 的激活剂。COTI-2 通过激活突变型 p53 和抑制 PI3K/AKT/mTOR 途径发挥作用。COTI-2 诱导多种人肿瘤细胞凋亡 (apoptosis)。COTI-2 通过 p53 依赖和非依赖机制在 HNSCC 中具有抗肿瘤活性。COTI-2 将突变型 p53 转化为野生型构象。

研究领域：Apoptosis

作用靶点：MDM-2/p53  |  Apoptosis

In Vitro: COTI-2 efficiently inhibits the proliferation rate of all the tested cell lines following 72 h of treatment. COTI-2 is significantly effective at inhibiting tumor cell proliferation in all three cell lines (COLO-205, HCT-15, and SW620). Relatively low concentrations of COTI-2 are active against all human glioblastoma cell lines tested (U87-MG, SNB-19, SF-268, and SF-295). COTI-2 treatment of SHP-77 cells with approximate IC₅₀ concentrations results in the induction of early apoptosis among 40 to 47% of total cells.

In Vivo: COTI-2 significantly inhibits tumor growth in the HT-29 human colorectal tumor xenografts at a dose of 10 mg/kg. In addition to reducing tumor volumes at specific times post-treatment, COTI-2 also delays the time required for tumors to reach specified volumes. COTI-2 also significantly inhibits tumor growth in the SHP-77 SCLC xenograft model at a dose as low as 3 mg/kg. COTI-2 treatment both reduces U87-MG tumor volumes at specific times post-treatment and lengthens the time required for U87-MG xenografts to grow in nude mice. Control tumors in mice treated with vehicle alone take only 5 days to reach an average volume of 828 mm³ while tumors in animals treated with COTI-2 take double that time (10 days) to reach a similar mean volume (857 mm³). COTI-2 treatment effectively inhibits OVCAR-3 xenograft growth regardless of the route of administration.

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