MTP 131 acetate

• CAT Number: I032867
• CAS Number: 1334953-95-5
• Molecular Formula: C34H53N9O7
• Molecular Weight: 699.854
• Purity: 98%
• Synonyms: MTP 131 acetate; MTP131 acetate; MTP-131 acetate; Elamipretide; SS-31; SS31; SS 31
• IUPAC Name: (S)-6-amino-N-((S)-1-amino-1-oxo-3-phenylpropan-2-yl)-2-((S)-2-((R)-2-amino-5-guanidinopentanamido)-3-(4-hydroxy-2,6-dimethylphenyl)propanamido)hexanamide acetate
• InChI: InChI=1S/C32H49N9O5.C2H4O2/c1-19-15-22(42)16-20(2)23(19)18-27(41-29(44)24(34)11-8-14-38-32(36)37)31(46)39-25(12-6-7-13-33)30(45)40-26(28(35)43)17-21-9-4-3-5-10-21;1-2(3)4/h3-5,9-10,15-16,24-27,42H,6-8,11-14,17-18,33-34H2,1-2H3,(H2,35,43)(H,39,46)(H,40,45)(H,41,44)(H4,36,37,38);1H3,(H,3,4)/t24-,25+,26+,27+;/m1./s1
• InChIKey: UEYRJRBULBAAEG-NFWUDPOKSA-N
• SMILES: O=C(N)[C@H](CC1=CC=CC=C1)NC([C@H](CCCCN)NC([C@H](CC2=C(C)C=C(O)C=C2C)NC([C@@H](CCCNC(N)=N)N)=O)=O)=O.CC(O)=O

MTP 131 is a mitochondria-targeted peptide antioxidant. It localizes to the mitochondria and reduces tert-butyl hydroperoxide-induced lipid peroxidation and apoptosis in SH-SY5Y cells when used at concentrations ranging from 0.001 to 1 nM.1 MTP 131 (2 mg/kg) reduces infarct volume, hemispheric swelling, and glutathione (GSH) depletion in a mouse model of acute cerebral ischemia induced by middle cerebral artery occlusion (MCAO). It increases survival, improves motor function, and decreases degeneration of the lumbar spinal cord in a superoxide dismutase 1 mutant (SOD1G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS) when administered at a dose of 5 mg/kg. MTP 131 reduces albuminuria, urinary hydrogen peroxide levels, and mesangial matrix accumulation, as well as preserves superoxide production, in a db/db mouse model of diabetic nephropathy.

Reference

1: Ballarò R, Lopalco P, Audrito V, Beltrà M, Pin F, Angelini R, Costelli P, Corcelli A, Bonetto A, Szeto HH, O’Connell TM, Penna F. Targeting Mitochondria by SS-31 Ameliorates the Whole Body Energy Status in Cancer- and Chemotherapy- Induced Cachexia. Cancers (Basel). 2021 Feb 18;13(4):850. doi: 10.3390/cancers13040850. PMID: 33670497; PMCID: PMC7923037.
2: Zhang L, Feng M, Wang X, Zhang H, Ding J, Cheng Z, Qian L. Peptide Szeto‑Schiller 31 ameliorates doxorubicin‑induced cardiotoxicity by inhibiting the activation of the p38 MAPK signaling pathway. Int J Mol Med. 2021 Apr;47(4):63. doi: 10.3892/ijmm.2021.4896. Epub 2021 Mar 2. PMID: 33649779; PMCID: PMC7914074.
3: Graham ZA, DeBerry JJ, Cardozo CP, Bamman MM. A 50 kdyne contusion spinal cord injury with or without the drug SS-31 was not associated with major changes in muscle mass or gene expression 14 d after injury in young male mice. Physiol Rep. 2021 Feb;9(4):e14751. doi: 10.14814/phy2.14751. PMID: 33611851; PMCID: PMC7897452.
4: Wu Y, Hao C, Han G, Liu X, Xu C, Zou Z, Zhou J, Yin J. SS-31 ameliorates hepatic injury in rats subjected to severe burns plus delayed resuscitation via inhibiting the mtDNA/STING pathway in Kupffer cells. Biochem Biophys Res Commun. 2021 Mar 26;546:138-144. doi: 10.1016/j.bbrc.2021.01.110. Epub 2021 Feb 11. PMID: 33582556.
5: Gao R, Ren L, Zhou Y, Wang L, Xie Y, Zhang M, Liu X, Ke S, Wu K, Zheng J, Liu X, Chen Z, Liu L. Recurrent non-severe hypoglycemia aggravates cognitive decline in diabetes and induces mitochondrial dysfunction in cultured astrocytes. Mol Cell Endocrinol. 2021 Feb 2;526:111192. doi: 10.1016/j.mce.2021.111192. Epub ahead of print. PMID: 33545179.
6: Tang H, Fang C, Xue S, Zhao G, Shi Z, Fu W, Zhang P, Tang X, Guo D. Protective effects of SS-31 against SDHB suppression-mitochondrial dysfunction- EndMT axis-modulated CBT sclerosis and progression. Am J Transl Res. 2020 Nov 15;12(11):7603-7619. PMID: 33312392; PMCID: PMC7724343.
7: Zhang H, Alder NN, Wang W, Szeto H, Marcinek DJ, Rabinovitch PS. Reduction of elevated proton leak rejuvenates mitochondria in the aged cardiomyocyte. Elife. 2020 Dec 15;9:e60827. doi: 10.7554/eLife.60827. PMID: 33319746; PMCID: PMC7738186.
8: Smuder AJ, Roberts BM, Wiggs MP, Kwon OS, Yoo JK, Christou DD, Fuller DD, Szeto HH, Judge AR. Pharmacological targeting of mitochondrial function and reactive oxygen species production prevents colon 26 cancer-induced cardiorespiratory muscle weakness. Oncotarget. 2020 Sep 22;11(38):3502-3514. doi: 10.18632/oncotarget.27748. PMID: 33014286; PMCID: PMC7517961.
9: Zuo Y, Yin L, Cheng X, Li J, Wu H, Liu X, Gu E, Wu J. Elamipretide Attenuates Pyroptosis and Perioperative Neurocognitive Disorders in Aged Mice. Front Cell Neurosci. 2020 Aug 13;14:251. doi: 10.3389/fncel.2020.00251. PMID: 32903868; PMCID: PMC7439217.
10: Whitson JA, Bitto A, Zhang H, Sweetwyne MT, Coig R, Bhayana S, Shankland EG, Wang L, Bammler TK, Mills KF, Imai SI, Conley KE, Marcinek DJ, Rabinovitch PS. SS-31 and NMN: Two paths to improve metabolism and function in aged hearts. Aging Cell. 2020 Oct;19(10):e13213. doi: 10.1111/acel.13213. Epub 2020 Aug 11. PMID: 32779818; PMCID: PMC7576234.
11: Yang SK, Han YC, He JR, Yang M, Zhang W, Zhan M, Li AM, Li L, Na-Song, Liu YT, Wu XQ, Zhang Q, Wang JW, Zhang H. Mitochondria targeted peptide SS-31 prevent on cisplatin-induced acute kidney injury via regulating mitochondrial ROS-NLRP3 pathway. Biomed Pharmacother. 2020 Oct;130:110521. doi: 10.1016/j.biopha.2020.110521. Epub 2020 Jul 24. PMID: 32717631.
12: Chiao YA, Zhang H, Sweetwyne M, Whitson J, Ting YS, Basisty N, Pino LK, Quarles E, Nguyen NH, Campbell MD, Zhang T, Gaffrey MJ, Merrihew G, Wang L, Yue Y, Duan D, Granzier HL, Szeto HH, Qian WJ, Marcinek D, MacCoss MJ, Rabinovitch P. Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice. Elife. 2020 Jul 10;9:e55513. doi: 10.7554/eLife.55513. PMID: 32648542; PMCID: PMC7377906.
13: Anguiano T, Sahu A, Qian B, Tang WY, Ambrosio F, Barchowsky A. Arsenic Directs Stem Cell Fate by Imparting Notch Signaling Into the Extracellular Matrix Niche. Toxicol Sci. 2020 Oct 1;177(2):494-505. doi: 10.1093/toxsci/kfaa106. PMID: 32647881; PMCID: PMC7548290.
14: Chavez JD, Tang X, Campbell MD, Reyes G, Kramer PA, Stuppard R, Keller A, Zhang H, Rabinovitch PS, Marcinek DJ, Bruce JE. Mitochondrial protein interaction landscape of SS-31. Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):15363-15373. doi: 10.1073/pnas.2002250117. Epub 2020 Jun 17. PMID: 32554501; PMCID: PMC7334473.
15: Thoma A, Akter-Miah T, Reade RL, Lightfoot AP. Targeting reactive oxygen species (ROS) to combat the age-related loss of muscle mass and function. Biogerontology. 2020 Aug;21(4):475-484. doi: 10.1007/s10522-020-09883-x. Epub 2020 May 23. PMID: 32447556; PMCID: PMC7347670.
16: Kong D, Chen L, Huang W, Zhang Z, Wang L, Zhang F, Zheng S. Combined therapy with ligustrazine and paeonol mitigates hepatic fibrosis through destroying mitochondrial integrity of stellate cell. Am J Transl Res. 2020 Apr 15;12(4):1255-1266. PMID: 32355539; PMCID: PMC7191175.
17: Miyamoto S, Zhang G, Hall D, Oates PJ, Maity S, Madesh M, Han X, Sharma K. Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db/db mice against progression of diabetic kidney disease. J Biol Chem. 2020 May 22;295(21):7249-7260. doi: 10.1074/jbc.RA119.011110. Epub 2020 Apr 10. PMID: 32277051; PMCID: PMC7247302.
18: Mitchell W, Ng EA, Tamucci JD, Boyd KJ, Sathappa M, Coscia A, Pan M, Han X, Eddy NA, May ER, Szeto HH, Alder NN. The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action. J Biol Chem. 2020 May 22;295(21):7452-7469. doi: 10.1074/jbc.RA119.012094. Epub 2020 Apr 9. PMID: 32273339; PMCID: PMC7247319.
19: Morigi M, Perico L, Corna D, Locatelli M, Cassis P, Carminati CE, Bolognini S, Zoja C, Remuzzi G, Benigni A, Buelli S. C3a receptor blockade protects podocytes from injury in diabetic nephropathy. JCI Insight. 2020 Mar 12;5(5):e131849. doi: 10.1172/jci.insight.131849. PMID: 32161193; PMCID: PMC7141402.
20: Cheikhi A, Anguiano T, Lasak J, Qian B, Sahu A, Mimiya H, Cohen CC, Wipf P, Ambrosio F, Barchowsky A. Arsenic Stimulates Myoblast Mitochondrial Epidermal Growth Factor Receptor to Impair Myogenesis. Toxicol Sci. 2020 Jul 1;176(1):162-174. doi: 10.1093/toxsci/kfaa031. PMID: 32159786; PMCID: PMC7357174.