Necrostatin-1
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Hodoodo CAT#: H 522437

CAS#: 4311-88-0

Description: Necrostatin-1 is a potent and selective inhibitor of necroptosis, a mechanism of programmed cell death separate from apoptosis. Necrostatin-1 functions as an allosteric inhibitor of the death domain receptor-associated adaptor kinase RIP (RIP1) in the necroptosis pathway. While affecting this distinct cell death pathway, Necrostatin-1 does not present any perturbation of the Fas/TNFR triggered canonical apoptosis cascade. Necrostatin-1 inhibits RIP1 kinase the key upstream kinase involved in the activation of necroptosis (EC50=180nM).


Chemical Structure

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Necrostatin-1
CAS# 4311-88-0

Theoretical Analysis

Hodoodo Cat#: H 522437
Name: Necrostatin-1
CAS#: 4311-88-0
Chemical Formula: C13H13N3OS
Exact Mass: 259.08
Molecular Weight: 259.330
Elemental Analysis: C, 60.21; H, 5.05; N, 16.20; O, 6.17; S, 12.36

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1350 Ready to ship
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Synonym: Necrostatin-1; Necrostatin1; Necrostatin 1; Nec-1; Nec 1; Nec1

IUPAC/Chemical Name: 5-(1H-indol-3-ylmethyl)-3-methyl-2-thioxo-4-imidazolidinone

InChi Key: TXUWMXQFNYDOEZ-UHFFFAOYSA-N

InChi Code: InChI=1S/C13H13N3OS/c1-16-12(17)11(15-13(16)18)6-8-7-14-10-5-3-2-4-9(8)10/h2-5,7,11,14H,6H2,1H3,(H,15,18)

SMILES Code: O=C(C(CC1=CNC2=C1C=CC=C2)N3)N(C)C3=S

Appearance: Light yellow solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: Necrostatin-1 (Nec-1) is a necroptosis inhibitor that inhibits RIP1 kinase (EC50=182 nM).
In vitro activity: This study further detected the levels of hypoxia-inducible factor-1α (HIF-1α) and miR-26a, and found that the increases in HIF-1α (Figure 2A) and miR-26a expression (Figure 1S, p < 0.05) induced by H/R (hypoxia and reoxygenation) injury were inhibited by Nec-1 treatment in a time-dependent manner (p < 0.05). The levels of TRPC6 and PARP-1 expression were found to be downregulated following H/R treatment (Figures 2A and S1, p < 0.05), and this was consistent with results from a previous study. In contrast, treatment with Nec-1 and H/R increased the levels of TRPC6 and PARP-1 expression, suggesting involvement of the TRPC6/PARP-1 signaling pathway in H/R-induced injuries in HK-2 cells. The levels of RIP1, RIP3, and Sirtuin-2 expression, as key factors in triggering necroptosis, were increased following H/R treatment, and those increases were partially inhibited by Nec-1 (Figures 2A and S1, p < 0.05). Reference: Mol Ther Nucleic Acids. 2019 Sep 6; 17: 701–713. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706591/
In vivo activity: The role of SDF-1 in the pathogenesis of OA (osteoarthritis) has attracted more attention in recent years. In an in vivo experiment, ELISA indicated serum SDF-1 expression in DMM (destabilized medial meniscus) mice and sham mice. The levels of serum SDF-1α decreased by 30.5% in DMM + Nec-1 group at 8 weeks post-surgery compared with DMM group; this difference was statistically significant (Figure 5C). The tendency is consistent with the results of the cell experiments. The effects of Nec-1 on the expression of HMGB1 and TLR4 in the cartilage were also validated by ICH in the mouse model (Figures 5F,G). The results showed that Nec-1 significantly decreased the expression of HMGB1 and TLR4 in the cartilage of DMM + Nec-1 group compared with DMM group. Reference: Front Pharmacol. 2018; 9: 1378. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277802/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 14.0 54.00

Preparing Stock Solutions

The following data is based on the product molecular weight 259.33 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Shen B, Mei M, Pu Y, Zhang H, Liu H, Tang M, Pan Q, He Y, Wu X, Zhao H. Necrostatin-1 Attenuates Renal Ischemia and Reperfusion Injury via Meditation of HIF-1α/mir-26a/TRPC6/PARP1 Signaling. Mol Ther Nucleic Acids. 2019 Sep 6;17:701-713. doi: 10.1016/j.omtn.2019.06.025. Epub 2019 Jul 12. PMID: 31422287; PMCID: PMC6706591. 2. Han XA, Jie HY, Wang JH, Zhang XM, Wang J, Yu CX, Zhang JL, He J, Chen JQ, Lai KF, Sun EW. Necrostatin-1 Ameliorates Neutrophilic Inflammation in Asthma by Suppressing MLKL Phosphorylation to Inhibiting NETs Release. Front Immunol. 2020 Apr 24;11:666. doi: 10.3389/fimmu.2020.00666. PMID: 32391007; PMCID: PMC7194114. 3. Mou F, Mou C. Necrostatin-1 Alleviates Bleomycin-Induced Pulmonary Fibrosis and Extracellular Matrix Expression in Interstitial Pulmonary Fibrosis. Med Sci Monit. 2020 Feb 5;26:e919739. doi: 10.12659/MSM.919739. PMID: 32019905; PMCID: PMC7020761. 4. Liang S, Lv ZT, Zhang JM, Wang YT, Dong YH, Wang ZG, Chen K, Cheng P, Yang Q, Guo FJ, Lu WW, Zhu WT, Chen AM. Necrostatin-1 Attenuates Trauma-Induced Mouse Osteoarthritis and IL-1β Induced Apoptosis via HMGB1/TLR4/SDF-1 in Primary Mouse Chondrocytes. Front Pharmacol. 2018 Nov 27;9:1378. doi: 10.3389/fphar.2018.01378. PMID: 30542285; PMCID: PMC6277802.
In vitro protocol: 1. Shen B, Mei M, Pu Y, Zhang H, Liu H, Tang M, Pan Q, He Y, Wu X, Zhao H. Necrostatin-1 Attenuates Renal Ischemia and Reperfusion Injury via Meditation of HIF-1α/mir-26a/TRPC6/PARP1 Signaling. Mol Ther Nucleic Acids. 2019 Sep 6;17:701-713. doi: 10.1016/j.omtn.2019.06.025. Epub 2019 Jul 12. PMID: 31422287; PMCID: PMC6706591. 2. Han XA, Jie HY, Wang JH, Zhang XM, Wang J, Yu CX, Zhang JL, He J, Chen JQ, Lai KF, Sun EW. Necrostatin-1 Ameliorates Neutrophilic Inflammation in Asthma by Suppressing MLKL Phosphorylation to Inhibiting NETs Release. Front Immunol. 2020 Apr 24;11:666. doi: 10.3389/fimmu.2020.00666. PMID: 32391007; PMCID: PMC7194114.
In vivo protocol: 1. Mou F, Mou C. Necrostatin-1 Alleviates Bleomycin-Induced Pulmonary Fibrosis and Extracellular Matrix Expression in Interstitial Pulmonary Fibrosis. Med Sci Monit. 2020 Feb 5;26:e919739. doi: 10.12659/MSM.919739. PMID: 32019905; PMCID: PMC7020761. 2. Liang S, Lv ZT, Zhang JM, Wang YT, Dong YH, Wang ZG, Chen K, Cheng P, Yang Q, Guo FJ, Lu WW, Zhu WT, Chen AM. Necrostatin-1 Attenuates Trauma-Induced Mouse Osteoarthritis and IL-1β Induced Apoptosis via HMGB1/TLR4/SDF-1 in Primary Mouse Chondrocytes. Front Pharmacol. 2018 Nov 27;9:1378. doi: 10.3389/fphar.2018.01378. PMID: 30542285; PMCID: PMC6277802.

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1: Mattiolo P, Yuste VJ, Boix J, Ribas J. Autophagy exacerbates caspase-dependent apoptotic cell death after short times of starvation. Biochem Pharmacol. 2015 Oct 3. pii: S0006-2952(15)00631-0. doi: 10.1016/j.bcp.2015.09.021. [Epub ahead of print] PubMed PMID: 26441250.

2: Suzuki T, Kikuguchi C, Sharma S, Sasaki T, Tokumasu M, Adachi S, Natsume T, Kanegae Y, Yamamoto T. CNOT3 suppression promotes necroptosis by stabilizing mRNAs for cell death-inducing proteins. Sci Rep. 2015 Oct 6;5:14779. doi: 10.1038/srep14779. PubMed PMID: 26437789.

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5: Kharaziha P, Chioureas D, Baltatzis G, Fonseca P, Rodriguez P, Gogvadze V, Lennartsson L, Björklund AC, Zhivotovsky B, Grandér D, Egevad L, Nilsson S, Panaretakis T. Sorafenib-induced defective autophagy promotes cell death by necroptosis. Oncotarget. 2015 Sep 22. [Epub ahead of print] PubMed PMID: 26416459.

6: Zhu L, Zhang M, Liu Y, Wang Y, Ma X. Necrostatin-1 Protects Against Ischemia/Reperfusion Injury by Inhibition of RIP-1 (Receptor-Interacting Protein 1) in a Rat Flap Model. Plast Reconstr Surg. 2015 Oct;136(4 Suppl):33. doi: 10.1097/01.prs.0000472315.28383.8f. PubMed PMID: 26397525.

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8: Reddy AS, Abraham A, McClain SA, Clark RA, Ralen P, Sandoval S, Singer AJ. The Role of Necroptosis in Burn Injury Progression in a Rat Comb Burn Model. Acad Emerg Med. 2015 Oct;22(10):1181-6. doi: 10.1111/acem.12768. Epub 2015 Sep 16. PubMed PMID: 26375585.

9: Wu JR, Wang J, Zhou SK, Yang L, Yin JL, Cao JP, Cheng YB. Necrostatin-1 protection of dopaminergic neurons. Neural Regen Res. 2015 Jul;10(7):1120-4. doi: 10.4103/1673-5374.160108. PubMed PMID: 26330837; PubMed Central PMCID: PMC4541245.

10: Qiu X, Klausen C, Cheng JC, Leung PC. CD40 ligand induces RIP1-dependent, necroptosis-like cell death in low-grade serous but not serous borderline ovarian tumor cells. Cell Death Dis. 2015 Aug 27;6:e1864. doi: 10.1038/cddis.2015.229. PubMed PMID: 26313915; PubMed Central PMCID: PMC4558516.

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12: Ding W, Shang L, Huang JF, Li N, Chen D, Xue LX, Xiong K. Receptor interacting protein 3-induced RGC-5 cell necroptosis following oxygen glucose deprivation. BMC Neurosci. 2015 Aug 4;16:49. doi: 10.1186/s12868-015-0187-x. PubMed PMID: 26238997; PubMed Central PMCID: PMC4524047.

13: Skrzeczyńska-Moncznik J, Bzowska M, Nogieć A, Sroka A, Zarębski M, Vallières L, Guzik K. Rapid externalization of 27-kDa heat shock protein (HSP27) and atypical cell death in neutrophils treated with the sphingolipid analog drug FTY720. J Leukoc Biol. 2015 Oct;98(4):591-9. doi: 10.1189/jlb.3VMA1114-522RR. Epub 2015 Jul 27. PubMed PMID: 26216939.

14: Afonso MB, Rodrigues PM, Carvalho T, Caridade M, Borralho P, Cortez-Pinto H, Castro RE, Rodrigues CM. Necroptosis is a key pathogenic event in human and experimental murine models of non-alcoholic steatohepatitis. Clin Sci (Lond). 2015 Oct 1;129(8):721-39. doi: 10.1042/CS20140732. Epub 2015 Jun 15. PubMed PMID: 26201023.

15: Ikari A, Taga S, Watanabe R, Sato T, Shimobaba S, Sonoki H, Endo S, Matsunaga T, Sakai H, Yamaguchi M, Yamazaki Y, Sugatani J. Clathrin-dependent endocytosis of claudin-2 by DFYSP peptide causes lysosomal damage in lung adenocarcinoma A549 cells. Biochim Biophys Acta. 2015 Oct;1848(10 Pt A):2326-36. doi: 10.1016/j.bbamem.2015.07.003. Epub 2015 Jul 8. PubMed PMID: 26163137.

16: Yelamanchili SV, Lamberty BG, Rennard DA, Morsey BM, Hochfelder CG, Meays BM, Levy E, Fox HS. MiR-21 in Extracellular Vesicles Leads to Neurotoxicity via TLR7 Signaling in SIV Neurological Disease. PLoS Pathog. 2015 Jul 8;11(7):e1005032. doi: 10.1371/journal.ppat.1005032. eCollection 2015 Jul. PubMed PMID: 26154133; PubMed Central PMCID: PMC4496044.

17: Miki Y, Akimoto J, Moritake K, Hironaka C, Fujiwara Y. Photodynamic therapy using talaporfin sodium induces concentration-dependent programmed necroptosis in human glioblastoma T98G cells. Lasers Med Sci. 2015 Aug;30(6):1739-45. doi: 10.1007/s10103-015-1783-9. Epub 2015 Jun 25. PubMed PMID: 26109138.

18: Opel D, Schnaiter A, Dodier D, Jovanovic M, Gerhardinger A, Idler I, Mertens D, Bullinger L, Stilgenbauer S, Fulda S. Targeting inhibitor of apoptosis proteins by Smac mimetic elicits cell death in poor prognostic subgroups of chronic lymphocytic leukemia. Int J Cancer. 2015 Dec 15;137(12):2959-70. doi: 10.1002/ijc.29650. Epub 2015 Jul 31. PubMed PMID: 26096065.

19: Steinwascher S, Nugues AL, Schoeneberger H, Fulda S. Identification of a novel synergistic induction of cell death by Smac mimetic and HDAC inhibitors in acute myeloid leukemia cells. Cancer Lett. 2015 Sep 28;366(1):32-43. doi: 10.1016/j.canlet.2015.05.020. Epub 2015 May 28. PubMed PMID: 26028172.

20: Rosentreter D, Funken D, Reifart J, Mende K, Rentsch M, Khandoga A. RIP1-Dependent Programmed Necrosis is Negatively Regulated by Caspases During Hepatic Ischemia-Reperfusion. Shock. 2015 Jul;44(1):72-6. doi: 10.1097/SHK.0000000000000371. PubMed PMID: 26009812.