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Mirdametinib

CAS No. : 391210-10-9

MCE 站：Mirdametinib

产品活性：Mirdametinib (PD0325901) 是一种具有口服活性，选择性和非 ATP 竞争性的 MEK 抑制剂，IC₅₀ 为 0.33 nM。Mirdametinib 对活化的 MEK1 和 MEK2 的 K_i^app 值为 1 nM。Mirdametinib 抑制 p-ERK1/2 的表达并诱导细胞凋亡 (apoptosis)。Mirdametinib 对多种人类肿瘤异种移植物具有抗癌活性。

研究领域：MAPK/ERK Pathway  |  Autophagy  |  Apoptosis

作用靶点：MEK  |  Autophagy  |  Apoptosis

In Vitro: Mirdametinib (PD325901; 0.0064, 0.032, 0.16, 0.8, 4, 20, 100 nM; for 2 days) inhibits the growth of Papillary thyroid carcinomas (PTC) cell lines (TPC-1 cells and K2 cells) with GC₅₀ of 11 nM and 6.3 nM, respectively.
Mirdametinib (100 nmol/L; for 4 days) induces apoptosis in K2 cells (top) or TPC-1 cells.
Mirdametinib (0.1, 1, 10, 100, 1000 nM; for 1 hour) suppresses the expression of p-ERK1/2 in K2 cells (top) or TPC-1 cells.
Mirdametinib prevents the growth of melanoma cell lines. Mirdametinib significantly prevents the the growth of PTC cells harboring a BRAF mutation at very low concentration (10 nM).

In Vivo: Mirdametinib (25 mg/kg, p.o.) inhibits phosphorylation of ERK by more than 50% at 24 hours post-dosing. Mirdametinib (25 mg/kg/day; po) produces a 70% incidence of complete tumor responses (C26 model).
Mirdametinib (20-25 mg/kg/day; oral gavage; for 3 weeks (5 consecutive days/week)) suppresses tumor growth completely in mice inoculated with PTC cells carrying a BRAF mutation (K2) and significantly decreased tumor growth in mice inoculated with PTC cells carrying the RET/PTC1 rearrangement (TPC-1) in athymic Ncr-nu/nu mice at ages 6 to 8 weeks.

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