GEM144 是一种有效且具有口服活性的DNA polymerase α(POLA1) 和HDAC 11双重抑制剂。GEM144 诱导p53乙酰化、激活p21、G1/S 细胞周期阻滞和细胞凋亡 (apoptosis)。
| 生物活性 | GEM144 is a potent and orally activeDNA polymerase α(POLA1) andHDAC11dual inhibitor. GEM144 induces acetylation ofp53, activation ofp21, G1/S cell cycle arrest, andapoptosis. GEM144 has significant antitumor activity in human orthotopic malignant pleural mesothelioma xenografts[1]. |
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体外研究
(In Vitro) | GEM144 (0-10 μM; 24 hours) exhibits antiproliferative activity in tested cancer cell lines with IC50s of 0.26 ~ 2.2 μM[1].
GEM144 (0.1 - 0.4 μM; 24 hours) strongly increases levels of H2AX phosphorylation on Ser 39 (γH2AX), and strongly upregulates p21 expression in a dose-dependent manner[1].
GEM144 (0.26 μM in NCI-H4609, 0.95 μM in A2780 and 1.4 μM in MM473; 72 hours) induced G1/S cell cycle arrest[1].
Cell Proliferation Assay | Cell Line: | NCI-H460, H460-R9A, A2780 and A2780-DX[1] | | Concentration: | 0-10 μM | | Incubation Time: | 24 hours (further 48 h growth in drug-free medium) | | Result: | Exhibited antiproliferative activity in tested cancer cell lines with IC50s of 0.26 ~ 2.2 μM. |
Western Blot Analysis | Cell Line: | NCI-H460[1] | | Concentration: | 0.1 μM, 0.25 μM and 0.4 μM | | Incubation Time: | 24 hours | | Result: | Strongly increased levels of H2AX phosphorylation on Ser 39 (γH2AX), and strongly upregulated p21 expression in a dose-dependent manner. |
Cell Cycle Analysis | Cell Line: | NCI-H4609, A2780 and MM473[1] | | Concentration: | 0.26 μM in NCI-H4609, 0.95 μM in A2780 and 1.4 μM in MM473 | | Incubation Time: | 72 hours | | Result: | Induced G1/S cell cycle arrest. |
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体内研究
(In Vivo) | GEM144 (50 mg/kg; p.o., bid, 5 days a week, for 3-4 weeks) significantly reduces tumor burden of MM487 with TGI of 72% in xenografts mice[1].
| Animal Model: | Female CD-1 nude mice (injected with MM473 and MM487)[1] | | Dosage: | 50 mg/kg | | Administration: | PO, bid, 5 days a week, for 3-4 weeks | | Result: | Significantly reduced tumor burden of MM487 with TGI of 72%. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
