| Identification | Back Directory | [Name]
2-Propenoic acid, 3-[4'-[2-(hydroxyamino)-2-oxoethoxy]-3'-tricyclo[3.3.1.13,7]dec-1-yl[1,1'-biphenyl]-4-yl]-, (2E)- | [CAS]
2217671-64-0 | [Synonyms]
MIR002
2-Propenoic acid, 3-[4'-[2-(hydroxyamino)-2-oxoethoxy]-3'-tricyclo[3.3.1.13,7]dec-1-yl[1,1'-biphenyl]-4-yl]-, (2E)- | [Molecular Formula]
C27H29NO5 | [MOL File]
2217671-64-0.mol | [Molecular Weight]
447.52 |
| Hazard Information | Back Directory | [Uses]
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]. | [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]. | 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). |
| [IC 50]
HDAC11: 6.09 μM (IC50); POLA1 | [References]
[1] Dallavalle S, et al. Antitumor activity of novel POLA1-HDAC11 dual inhibitors. Eur J Med Chem. 2022, 228:113971. DOI:10.1016/j.ejmech.2021.113971 |
|
|