MIR002

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上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

MIR002 

MIR002 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。MIR002 诱导 p53 的乙酰化、p21 的激活、G1/S 细胞周期停滞和细胞凋亡apoptosis。MIR002 显示出显著的体内抗肿瘤活性。

MIR002

MIR002 Chemical Structure

CAS No. : 2217671-64-0

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生物活性

MIR002 is a potent and orally active DNA polymerase α (POLA1) and HDAC 11 dual inhibitor. MIR002 induces acetylation of p53, activation of p21, G1/S cell cycle arrest, and apoptosis. MIR002 shows significant antitumor activity in vivo[1].

IC50 & Target

HDAC11

6.09 μM (IC50)

POLA1

 

体外研究
(In Vitro)

MIR002 (24 h) shows antiproliferative activity at nanomolar concentrations (IC50s of 0.25, 2.8, 0.6, 0.41 µM in NCI-H460, H460-R9A, A2780, A2780-DX; IC50s of 0.9, 1.2, 0.22, 0.71, 2.1, 0.52, 0.038, 0.18, 0.42, 1.9, 0.64, 1.1 µM in MM432, MM473, MM487, RAMOS, L-428, U-293, Z-138, NB4, THP-1, MDA-MB231, MDA-MB436, U87MG cells, respectively)[1].
MIR002 (0.0001,0.01, 1, 10 µM) shows inhibitory activity on HDAC11 with an IC50 of 6.09 µM[1].
MIR002 (0.1, 0.25, 0.4 µM, 24 h) shows a dose-dependent p53 acetylation and p21 induction as well as H2AX Phosphorylation[1]. MIR002 (72 h) leads to cell cycle arrest at the G1-S phase[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay[1]

Cell Line: MM432, MM473, MM487, RAMOS, L-428, U-293, Z-138, NB4, THP-1, MDA-MB231, MDA-MB436, U87MG cells
Concentration: 10 scalar concentrations
Incubation Time: 24 h
Result: Showed antiproliferative activity at nanomolar concentrations (IC50s of 0.9, 1.2, 0.22, 0.71, 2.1, 0.52, 0.038, 0.18, 0.42, 1.9, 0.64, 1.1 µM in MM432, MM473, MM487, RAMOS, L-428, U-293, Z-138, NB4, THP-1, MDA-MB231, MDA-MB436, U87MG cells, respectively)

Western Blot Analysis[1]

Cell Line: NCI-H460, MM473, MM487, A2780 cells
Concentration: 0.1, 0.25, 0.4 µM
Incubation Time: 24 h
Result: Showed antiproliferative activity at nanomolar concentrations (IC50s of 0.9, 1.2, Showed a dosedependent p53 acetylation and p21 induction as well as H2AX Phosphorylation.

Cell Cycle Analysis[1]

Cell Line: NCI-H460, A2780, MM473, H460-R9A cells
Concentration: 0.25 µM for NCI-H460, 0.6 µM for A2780, 1.2 µM for MM473, 2.8 µM for H460-R9A
Incubation Time: 72 h
Result: Cells were arrested at the G1-S phase.

体内研究
(In Vivo)

MIR002 (50 mg/kg; p.o.; twice a day for 5 days a week, 3 weeks) shows a good tolerability and antitumor activity (TGI=61%)[1].
MIR002 (50 mg/kg; p.o.; twice a day for 5 days a week, 6 weeks) shows an additive antitumor effect with complete disappearance of tumor masses in two animals at the end of the treatment when combination with cisplatin[1].
MIR002 ( 50 mg/kg, twice a day for 5 days) induces a significant increase of a interferon at its pharmacological active dose (50 mg/kg)[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Model: 4-6 weeks old female CD-1 nude mice (NSCLC NCI-H460 model)
Dosage: 50 mg/kg
Administration: p.o.; twice a day for 5 days a week, 3 weeks
Result: Showed a good tolerability and antitumor activity (TGI=61%).
Animal Model: 4-6 weeks old female CD-1 nude mice ( MM473-luc and MM487-Luc)[1]
Dosage: 50 mg/kg combibnated with cisplatin (i.p.; 5 mg/kg; twice a day for 7 days a week, 6 weeks)
Administration: p.o.; twice a day for 5 days a week, 6 weeks
Result: Showed an additive antitumor effect with complete disappearance of tumor masses in two animals at the end of the treatment when combination with cisplatin.
Animal Model: 4-6 weeks old female CD-1 nude mice (Melanoma B16 model)[1]
Dosage: 50 mg/kg
Administration: p.o.; twice a day for 5 days
Result: Induced a significant increase of α interferon at its pharmacological active dose (50 mg/kg).

分子量

461.55

Formula

C28H31NO5
CAS 号

2217671-64-0
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.
参考文献

  • [1]. Dallavalle S, et al. Antitumor activity of novel POLA1-HDAC11 dual inhibitors. Eur J Med Chem. 2022, 228:113971.

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