الصفحة الرئيسية>>Signaling Pathways>> DNA Damage/DNA Repair>> ATM/ATR>>Mirin

Mirin

رقم الكتالوجGC13491

ميرين هو مثبط جزيء صغير لمركب MRN (Mre11 و Rad50 و Nbs1).

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Mirin التركيب الكيميائي

Cas No.: 1198097-97-0

الحجم السعر المخزون الكميّة
10mM (in 1mL DMSO)
38٫00
متوفر
10mg
68٫00
متوفر
50mg
225٫00
متوفر

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Sample solution is provided at 25 µL, 10mM.

Description of Mirin

Mirin is an inhibitor of Mre11-Rad50-Nbs1 (MRN) complex (IC50=12μM), which can inhibit the activity of MRE11-related exonuclease, and can inhibit the activation of MRN-dependent ATM[1]. It is commonly used in the study of cancers related to DNA repair mechanisms[1].

Mirin (100µM, 24 hours) significantly enhanced the sensitivity of human papillomavirus (HPV) to N-methylpyrrole-imidazole hairpin polyamide (PA25)[2]. Mirin (50μM, 24h) significantly enhanced DNA double-strand breaks and promoted cell apoptosis in esophageal squamous cell carcinoma (ESCC) cells treated with NU7441 and ionizing radiation treatment[3].

Mirin (50mg/kg/day, 9 days, intratumoral injection) efficiently restrains tumor growth in Neuroblastoma mouse model by inducing DNA damage response (DDR) and apoptosis[4]. Mirin (50mg/kg, 72 hours, i.p.) significantly increased tubular damage and serum markers of acute kidney injury (AKI) (creatinine and neutrophil gelatinase-associated lipocalin) in cisplatin-induced nephrotoxic AKI mouse model[5].

References:
[1] Dupré A, Boyer-Chatenet L, Sattler RM, et al. A forward chemical genetic screen reveals an inhibitor of the Mre11–Rad50–Nbs1 complex. Nature chemical biology. 2008 Feb;4(2):119-25.
[2] Edwards TG, Vidmar TJ, Koeller K, et al. DNA damage repair genes controlling human papillomavirus (HPV) episome levels under conditions of stability and extreme instability. PloS one. 2013 Oct 2;8(10):e75406.
[3] Wang G, Guo S, Zhang W, et al. A comprehensive analysis of alterations in DNA damage repair pathways reveals a potential way to enhance the radio-sensitivity of esophageal squamous cell cancer. Frontiers in oncology. 2020 Oct 16;10:575711.
[4] Petroni M, Sardina F, Infante P, et al. MRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors. Cell death & disease. 2018 Aug 30;9(9):895.
[5] Hama T, Nagesh PK, Chowdhury P, et al. DNA damage is overcome by TRIP13 overexpression during cisplatin nephrotoxicity. JCI insight. 2021 Nov 11;6(22).

Protocol of Mirin

Cell experiment [1]:

Cell lines

W12E cells

Preparation Method

W12E cells were pre-treated with 100µM Mirin or 0.1% DMSO for 24h. Media was removed and fresh media containing the indicated doses of N-methylpyrrole-imidazole hairpin polyamide (PA25) or 0.1% DMSO was added, and cells incubated an additional 24h.

Reaction Conditions

100µM, 24 hours

Applications

Mirin significantly sensitized human papillomavirus (HPV) episomes to PA25.
Animal experiment [2]:

Animal models

Neuroblastoma mouse model

Preparation Method

1. Mirin encapsulation in biocompatible polymeric nanocarriers:
250mg PLGA-b-PEG-COOH (10kDa, 0.025mmol) and 50mg of Mirin (0.23mmol) were dissolved in 25mL of DMSO. The organic phase was mixed to 250mL of ultrapure water under vigorous stirring for 30min, maintaining water/organic ratio 10/1 with a constant removal of the resulting solution. The mixture was subsequently purified and concentrated using centrifugal filter devices to a final volume of 20mL, passed through a filter SterivexTM-GP 0.22μm of polyether sulfone and stored at 4°C. The same procedure was exploited to obtain empty nanoparticles.

2. Mice were randomized and injected daily with Mirin (50mg/kg/d) or vehicle (empty nanoparticles), totally 9 days according to the indicated schedule (arrowheads).

Dosage form

50mg/kg/d, 9 days, intratumoral injection

Applications

Mirin efficiently restrains tumor growth in vivo by inducing DNA damage response (DDR) and apoptosis.

Chemical Properties of Mirin

Cas No. 1198097-97-0 SDF
Chemical Name (Z)-5-(4-hydroxybenzylidene)-2-imino-2,5-dihydrothiazol-4-ol
Canonical SMILES N=C1N=C(O)/C(S1)=C([H])/C2=CC=C(O)C=C2
Formula C10H8N2O2S M.Wt 220.25
الذوبان ≥ 9.3mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table of Mirin

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 4.5403 mL 22.7015 mL 45.403 mL
5 mM 0.9081 mL 4.5403 mL 9.0806 mL
10 mM 0.454 mL 2.2701 mL 4.5403 mL
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In vivo Formulation Calculator (Clear solution) of Mirin

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Product Documents

Quality Control & SDS

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Review for Mirin

Average Rating: 5 ★★★★★ (Based on Reviews and 9 reference(s) in Google Scholar.)

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