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

Katalog-Nr.GC11008

Ein RIP1-Kinase-Inhibitor

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Necrostatin-1 Chemische Struktur

Cas No.: 4311-88-0

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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 wirkt hauptsächlich auf RIP1 in Zellen [5]. Necrostatin-1 ist ein RIP1-Kinase-Inhibitor mit einem IC50-Wert von 0,32 mM[1]. Necrostatin-1 kann die Autophosphorylierung von RIP1 effektiv hemmen und blockiert die Signalübertragung von RIP1-RIP3-MLKL durch Hemmung der Phosphorylierung von RIP1 [7]. Necrostatin-1 ist auch ein IDO-Inhibitor[2].

Unter oxidativem Stress zeigte CMPC hauptsächlich ein nekrotisches Phänotyp und durch Vorbehandlung mit Necrostatin-1 beobachteten wir eine 37 ± 8%ige Reduktion des nekrotischen Zelltods bei CMPC im Vergleich zum Fahrzeug. Es wurden keine Unterschiede in der apoptotischen Zellsterblichkeit festgestellt. Daher erhöhte Necrostatin-1 das Überleben von CMPCs, indem es den nekrotischen Zelltod hemmte [4] . Die Verhältnisse von apoptotischen und nekrotischen C2C12-Zellen nahmen nach CoCl2-Behandlung zu, typische morphologische Merkmale der Nekroptose konnten mittels TEM beobachtet werden, während Necrostatin-1 eine schützende Wirkung gegen durch CoCl2 induzierten oxidativen Stress aufwies. Die Behandlung mit Necrostatin-1 verringerte signifikant die RIP1-, pERK1/2-, HIF 1α-, BNIP3- und ROS-Spiegel, die durch CoCl2 verursacht wurden, und förderte die Differenzierung von C2C12. Necrostatin-1 kehrte die durch CoCl2 verursachte Abnahme des mitochondrialen Membranpotentials um [6] .

Bei Mäusen verhinderte Necrostatin-1 (Nec-1), ein spezifischer Inhibitor der Kinase-Domäne des Rezeptor-interagierenden Proteins 1 (RIP1), osmotische Nephrose und CIAKI, während eine inaktive Derivat von Necrostatin-1 (Nec-1i) oder der Pan-Caspase-Inhibitor zVAD dies nicht taten. Necrostatin-1 verhinderte die RCM-induzierte Dilatation peritubulärer Kapillaren und legt nahe, dass es eine neue Rolle gibt, die nichts mit dem Zelltod zu tun hat, für die RIP1-Kinase-Domäne bei der Regulation der Mikrovaskulatur-Hämodynamik und Pathophysiologie von CIAKI[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
Überlieferungen 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
Löslichkeit ≥ 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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