Necrostatin-1 (Synonyms: MTH-DL-Tryptophan,Nec-1) |
| Katalog-Nr.GC11008 |
Ein RIP1-Kinase-Inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 4311-88-0
Sample solution is provided at 25 µL, 10mM.
Necrostatin-1 mainly acts on RIP1 in cells [5], Necrostatin-1 is a RIP1 kinase inhibitor with an IC50 value of 0.32 mM[1]. Necrostatin-1 can effectively inhibit RIP1 autophosphorylation, Necrostatin-1 effectively blocks RIP1-RIP3-MLKL signaling by inhibiting RIP1 phosphorylation [7]. Necrostatin-1 is also an IDO inhibitor[2].
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 [4]. The ratios of apoptotic and necrotic C2C12 cells were increased following CoCl2 treatment, typical necroptotic morphological characteristics were able to observe by TEM, whereas Necrostatin-1 exhibited a protective effect against CoCl2 induced oxidative stress. Treatment with Necrostatin-1 significantly decreased the levels of RIP1, p ERK1/2, HIF 1α, BNIP3 and ROS induced by CoCl2, and promoted C2C12 differentiation. Necrostatin-1 reversed the CoCl2 induced decrease in mitochondrial membrane potential [6].
In mice,Necrostatin-1 (Nec-1), a specific inhibitor of the receptor-interacting protein 1 (RIP1) kinase domain, prevented osmotic nephrosis and CIAKI, whereas an inactive Necrostatin-1 derivate (Nec-1i) or the pan-caspase inhibitor zVAD did not. Necrostatin-1 prevented RCM-induced dilation of peritubular capillaries, suggesting a novel role unrelated to cell death for the RIP1 kinase domain in the regulation of microvascular hemodynamics and pathophysiology of 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.
| Kinase experiment [1]: | |
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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. |
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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) |
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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 |
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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. |
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| 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. | ||
| Prepare stock solution | |||
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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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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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