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Necrostatin-1 (Synonyms: MTH-DL-Tryptophan,Nec-1)

カタログ番号GC11008

RIP1キナーゼ阻害剤

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Necrostatin-1 化学構造

Cas No.: 4311-88-0

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10mM (in 1mL DMSO)
$40.00
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10mg
$34.00
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50mg
$90.00
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100mg
$134.00
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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 7 publications

Product Documents

Quality Control & SDS

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Protocol

Kinase experiment [1]:

Preparation Method

Cells were lysed, Immunoprecipitation was carried out for 16 h at 4 °C using anti-FLAG M2 agarose beads, Beads were incubated in 15 ul of the reaction buffer for 15 min at 23-25 °C in the presence of different concentrations of necrostatins (including Necrostatin-1). Kinase reaction was initiated by addition of 10 μM cold ATP and 1 μCi of [y-32P]ATP, and reactions were carried out for 30 min at 30°C.

Reaction Conditions

RIP1 kinase assay( Necrostatin-1) was performed at 30°C for 30 min

Applications

Necrostatin-1 is a RIP1 kinase inhibitor, RIP1 is the primary cellular target responsible for the antinecroptosis activity of necrostatin-1.

Cell experiment [2]:

Cell lines

Cardiomyocyte progenitor cells (CMPCs)

Preparation Method

CMPCs were pretreated with vehicle or Necrostatin-1 for 30 min prior to the addition of tert-Butyl hydroperoxide in serum-free M199 medium.

Reaction Conditions

30 µM Necrostatin-1 for 30 min

Applications

Under oxidative stress conditions, CMPC mainly displayed a necrotic phenotype and by pretreatment with Necrostatin-1, we observed a 37 ± 8% reduction in necrotic cell death in CMPCs compared with vehicle. Not find differences in apoptotic-mediated cell death. Therefore, Necrostatin-1 increased the survival of CMPCs by inhibiting necrotic cell death.

Animal experiment [3]:

Animal models

Eight-week-old male C57Bl/6 mice

Preparation Method

Mice undergo sham surgery or bilateral renal pedicle clamping 24 hours before intraperitoneal injection of either PBS, the highly specific RIP1 kinase inhibitor Necrostatin-1, or the inactive derivate of necrostatin-1 (Necrostatin-1i) in the presence or absence of RCM.

Dosage form

Necrostatin-1 (1.65 mg/kg body weight) was applied intraperitoneally 15 min before RCM-injection.

Applications

CIAKI Is Attenuated by Necrostatin-1, an Inhibitor of the Kinase Domain of Receptor-Interacting Protein Kinase-1.

References:

[1]. Degterev A, Hitomi J,et,al.Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol. 2008 May;4(5):313-21. doi: 10.1038/nchembio.83. PMID: 18408713; PMCID: PMC5434866.

[2]. Feyen D, Gaetani R,et,al. Increasing short-term cardiomyocyte progenitor cell (CMPC) survival by necrostatin-1 did not further preserve cardiac function. Cardiovasc Res. 2013 Jul 1;99(1):83-91. doi: 10.1093/cvr/cvt078. Epub 2013 Apr 3. PMID: 23554461.

[3]. Linkermann A, Heller JO,et,al. Nec-1The RIP1-kinase inhibitor necrostatin-1 prevents osmotic nephrosis and contrast-induced AKI in mice. J Am Soc Nephrol. 2013 Oct;24(10):1545-57. doi: 10.1681/ASN.2012121169. Epub 2013 Jul 5. Erratum in: J Am Soc Nephrol. 2014 Dec;25(12):2942. PMID: 23833261; PMCID: PMC3785275.

Background

Necrostatin-1は、細胞内で主にRIP1に作用します[5]。IC50値が0.32 mMのRIP1キナーゼ阻害剤であり、効果的にRIP1オートフォスホリレーションを抑制し、RIP1-RIP3-MLKLシグナル伝達を阻害することができます[7]。また、Necrostatin-1はIDO阻害剤でもあります[2]

酸化ストレス条件下では、CMPCは主に壊死的フェノタイプを示し、Necrostatin-1の前処理により、車両と比較して37±8%の壊死細胞死が減少したことが観察されました。アポトーシス媒介性細胞死に差異は見られませんでした。したがって、Necrostatin-1は壊死的細胞死を抑制することにより、CMPCの生存率を増加させました[4]。CoCl2処理後、アポトーシスおよび壊死C2C12細胞の比率が増加し、TEMで典型的なネクロプトーシス形態学的特徴が観察されました。一方でNecrostatin-1はCoCl2誘導性酸化ストレスに対して保護効果を示しました。Necrostatin-1投与はRIP1、p ERK1/2、HIF 1α、BNIP3およびROSレベルを有意に低下させると同時にC2C12分化を促進しました。またNecrostatin-1はCoCl2誘導性ミトコンドリア膜電位低下を逆転させました[6]

マウスにおいて、レセプター相互作用性タンパク質1(RIP1)キナーゼドメインの特異的阻害剤であるネクロスタチン-1(Nec-1)は、浸透圧性腎症とCIAKIを防止しました。一方、非活性なネクロスタチン-1誘導体(Nec-1i)やパンカスパーゼ阻害剤zVADでは効果がありませんでした。また、Necrostatin-1は周管間拡張を抑制することにより微小血管の血液動態の調節及びCIAKIの病態生理学に関連する新たな役割があることが示唆されました[3]。

References:
[1]: Xie T, Peng W, et,al. Structural basis of RIP1 inhibition by necrostatins. Structure. 2013 Mar 5;21(3):493-9. doi: 10.1016/j.str.2013.01.016. PMID: 23473668.
[2]: Degterev A, Huang Z, et,al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 2005 Jul;1(2):112-9. doi: 10.1038/nchembio711. Epub 2005 May 29. Erratum in: Nat Chem Biol. 2005 Sep;1(4):234. PMID: 16408008.
[3]: Linkermann A, Heller JO, et,al. The RIP1-kinase inhibitor necrostatin-1 prevents osmotic nephrosis and contrast-induced AKI in mice. J Am Soc Nephrol. 2013 Oct;24(10):1545-57. doi: 10.1681/ASN.2012121169. Epub 2013 Jul 5. Erratum in: J Am Soc Nephrol. 2014 Dec;25(12):2942. PMID: 23833261; PMCID: PMC3785275.
[4]: Feyen D, Gaetani R, et,al. Increasing short-term cardiomyocyte progenitor cell (CMPC) survival by necrostatin-1 did not further preserve cardiac function. Cardiovasc Res. 2013 Jul 1;99(1):83-91. doi: 10.1093/cvr/cvt078. Epub 2013 Apr 3. PMID: 23554461.
[5]: Degterev A, Hitomi J, et,al.Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol. 2008 May;4(5):313-21. doi: 10.1038/nchembio.83. PMID: 18408713; PMCID: PMC5434866.
[6]: Chen R, Xu J, et,al.Necrostatin-1 protects C2C12 myotubes from CoCl2-induced hypoxia. Int J Mol Med. 2018 May;41(5):2565-2572. doi: 10.3892/ijmm.2018.3466. Epub 2018 Feb 6. PMID: 29436688; PMCID: PMC5846651.
[7]: Degterev A, Huang Z, et,al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 2005 Jul;1(2):112-9. doi: 10.1038/nchembio711. Epub 2005 May 29. Erratum in: Nat Chem Biol. 2005 Sep;1(4):234. PMID: 16408008.

Chemical Properties

Cas No. 4311-88-0 SDF
同義語 MTH-DL-Tryptophan,Nec-1
Chemical Name 5-(1H-indol-3-ylmethyl)-3-methyl-2-sulfanylideneimidazolidin-4-one
Canonical SMILES CN1C(=O)C(NC1=S)CC2=CNC3=CC=CC=C32
Formula C13H13N3OS M.Wt 259.33
溶解度 ≥ 12.97 mg/mL in DMSO, ≥ 13.29 mg/mL in EtOH with ultrasonic 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

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1 mg 5 mg 10 mg
1 mM 3.8561 mL 19.2805 mL 38.5609 mL
5 mM 0.7712 mL 3.8561 mL 7.7122 mL
10 mM 0.3856 mL 1.928 mL 3.8561 mL
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