(Z)-Mirin functions as an inhibitor targeting the MRN complex, comprising Mre11, Rad50, and Nbs1, thereby obstructing the MRN-mediated initiation of ATM activation without influencing the kinase activity of ATM itself. It effectively suppresses the exonuclease activity associated with Mre11. The compound enhances apoptosis, induces a G2/M cell cycle arrest, and significantly diminishes the efficiency of homology-directed repair (HDR)[1].[2].
体外研究
At varying concentrations (50, 100, 500 μM), (Z)-Mirin curtails the ATM-dependent phosphorylation of Nbs1 and Chk2, along with the MRN-induced autophosphorylation of ATM at Ser1981 following DNA double-strand breaks (DSBs). A concentration of 100 μM of (Z)-Mirin is noted for its capacity to inhibit the nuclease functionality of Mre11[1].
Exposure to (Z)-Mirin ranging from 10 to 100 μM for 24 hours demonstrates a median cytotoxicity threshold at 50 μM in HEK293 cells[1].
Concentrations of 50 μM and 100 μM of (Z)-Mirin are reported to induce significant G2 phase arrest[1].
Furthermore, application of (Z)-Mirin at 18 µM for a duration of 48 hours leads to an upsurge in apoptotic activity within PEO4 cells[2].
Mirin 细胞实验
Cell Line
Concentration
Treated Time
Description
References
EJ-30 human bladder carcinoma cell line
20 μM
14 or 15 days
To investigate the inhibitory effect of Mirin on MRE11 3'–5' exonuclease activity and its impact on DNA double-strand break repair. Results showed that Mirin treatment reduced the frequency of large deletions and GCRs at both interstitial and subtelomeric DSBs, but had little effect on the frequency of small deletions.
Nucleic Acids Res. 2015 Sep 18;43(16):7911-30
LAN5
40 μM
48 hours
To evaluate the effect of Mirin on the proliferation and survival of LAN5 cells, results showed that Mirin significantly inhibited the proliferation of MYCN-amplified neuroblastoma cells.
Cell Death Dis. 2018 Aug 30;9(9):895
Kelly
40 μM
48 hours
To evaluate the effect of Mirin on the proliferation and survival of Kelly cells, results showed that Mirin significantly inhibited the proliferation of MYCN-amplified neuroblastoma cells.
Cell Death Dis. 2018 Aug 30;9(9):895
IMR32
40 μM
48 hours
To evaluate the effect of Mirin on the proliferation and survival of IMR32 cells, results showed that Mirin significantly inhibited the proliferation of MYCN-amplified neuroblastoma cells.
Cell Death Dis. 2018 Aug 30;9(9):895
A549 cells
25 μM
24 hours
Inhibition of MRE11 nuclease activity, leading to reduced HR efficiency.
Nucleic Acids Res. 2015 Mar 31;43(6):3154-66
HeLa cells
25 μM
24 hours
Inhibition of MRE11 nuclease activity, leading to reduced HR efficiency.
Nucleic Acids Res. 2015 Mar 31;43(6):3154-66
HT1080 cells
25 μM
1-hour pretreatment, continued until the end of the experiment
Inhibition of MRE11 exonuclease activity prevents degradation of newly replicated genome, reduces accumulation of self-DNA in the cytosol, and attenuates innate immune response signaling.
Nucleic Acids Res. 2017 May 5;45(8):4590-4605
IMR90-ER/RASV12 fibroblasts
10 μM
6 days
Mirin prevented RAS-induced SAHF formation in a dose-dependent manner.
Nat Commun. 2024 Jun 26;15(1):5423
BJ-RASV12 fibroblasts
10 μM
8 days
Mirin inhibited the exonuclease activity of MRE11, preventing RASV12-induced replication stress, micronuclei formation, and interferon response.
Nat Commun. 2024 Jun 26;15(1):5423
HeLa_XRCC1_KD cells
25 μM
24 hours
Mirin induced synthetic lethality in XRCC1-deficient cells, associated with DSB accumulation, S-phase arrest, and increased apoptosis
NPJ Precis Oncol. 2022 Jul 19;6(1):51
A2780_XRCC1_KO cells
25 μM
24 and 48 hours
Mirin induced synthetic lethality in XRCC1-deficient cells, associated with DSB accumulation, S-phase arrest, and increased apoptosis
NPJ Precis Oncol. 2022 Jul 19;6(1):51
PEO4 cells
10 μM
24 hours
Mirin pre-treatment increased platinum sensitivity, associated with DSB accumulation, S-phase arrest, and increased apoptotic cells
NPJ Precis Oncol. 2022 Jul 19;6(1):51
A2780cis cells
10 μM
24 hours
Mirin pre-treatment increased platinum sensitivity, associated with DSB accumulation, S-phase arrest, and increased apoptotic cells
NPJ Precis Oncol. 2022 Jul 19;6(1):51
HeLa_BRCA2_KD cells
18 µM
48 hours
To evaluate the cytotoxicity of Mirin in BRCA2-deficient HeLa cells, results showed that HeLa_BRCA2_KD cells were highly sensitive to Mirin, accompanied by DSB accumulation, G2/M cell cycle arrest, and increased apoptosis.
Int J Mol Sci. 2023 Jun 30;24(13):10966
PEO4 cells
18 µM
24 hours
To evaluate the cytotoxicity of Mirin in BRCA2-proficient cells, results showed that PEO4 cells were not sensitive to Mirin.
Int J Mol Sci. 2023 Jun 30;24(13):10966
PEO1 cells
18 µM
24 hours
To evaluate the cytotoxicity of Mirin in BRCA2-deficient cells, results showed that PEO1 cells were sensitive to Mirin, accompanied by DSB accumulation, G2/M cell cycle arrest, and increased apoptosis.
Int J Mol Sci. 2023 Jun 30;24(13):10966
HCT116 colon carcinoma cells
100 μM
40 minutes
Mirin inhibits MRE11 catalytic activity, leading to significantly impaired activation of CHK1 and CHK2 after irradiation.
Oncogene. 2018 Jan 25;37(4):427-438
HEK-293T cells
100 µM
24 hours
Inhibits mre-11 exonuclease activity and MRN complex, preventing DNA damage-induced CD47 upregulation
Commun Biol. 2023 Mar 7;6(1):245
Mirin 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
LAN5 neuroblastoma xenograft model
Local injection
50 mg/kg
Once daily for 11 days
To evaluate the effect of Mirin on tumor growth in the LAN5 neuroblastoma xenograft model, results showed that Mirin significantly inhibited tumor growth and induced DDR and apoptosis.
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