WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H402110
CAS#: 925434-55-5 (free base)
Description: SRT-1720, also known as CAY10559 and is a drug developed by Sirtris Pharmaceuticals intended as a small-molecule activator of the sirtuin subtype SIRT1. It has similar activity in the body to the known SIRT1 activator resveratrol, but is 1000x more potent. In animal studies it was found to improve insulin sensitivity and lower plasma glucose levels in fat, muscle and liver tissue, and increased mitochondrial and metabolic function. A study of SRT1720 conducted by the National Institute on Aging found that the drug may extend the lifespan of obese mice by 44% .
Hodoodo Cat#: H402110
Name: SRT-1720 free base
CAS#: 925434-55-5 (free base)
Chemical Formula: C25H23N7OS
Exact Mass: 469.17
Molecular Weight: 469.560
Elemental Analysis: C, 63.95; H, 4.94; N, 20.88; O, 3.41; S, 6.83
Related CAS #: 925434-55-5 (free base) 1001645-58-4 (HCl),
Synonym: SRT1720; SRT-1720; SRT 1720; CAY10559; CAY-10559; CAY 10559; SIRT-1933; SIRT 1933; SIRT1933.
IUPAC/Chemical Name: N-(2-(3-(piperazin-1-ylmethyl)imidazo[2,1-b]thiazol-6-yl)phenyl)quinoxaline-2-carboxamide
InChi Key: IASPBORHOMBZMY-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H23N7OS/c33-24(22-13-27-20-7-3-4-8-21(20)28-22)29-19-6-2-1-5-18(19)23-15-32-17(16-34-25(32)30-23)14-31-11-9-26-10-12-31/h1-8,13,15-16,26H,9-12,14H2,(H,29,33)
SMILES Code: O=C(C1=NC2=CC=CC=C2N=C1)NC3=CC=CC=C3C4=CN5C(SC=C5CN6CCNCC6)=N4
Appearance: white 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: | SRT 1720 is a selective activator of human SIRT1 with an EC1.5 of 0.16 μM and shows less potent activities agaiinst SIRT2 and SIRT3 with EC1.5s of 37 μM and > 300 μM, respectively. |
| In vitro activity: | MDA-MB-231 cells with stable expression of LC3-GFP were generated to measure the affect of SRT1720 on autophagy by observation of GFP punctae formation. Treatment with SRT1720 resulted in an increase in the number of cells with an average of 8 GFP punctae per cell (Fig. 3B). An immunoblot of LC3 will show an increase in the lower LC3-II band during autophagy. It was observed that treatment with SRT1720 caused an increase in the autophagy marker LC3-II, and this was decreased in sh-SIRT1 knockdown MDA-MB-231 cells (Fig. 3C). Next, it was determined whether blocking the PI3K pathway responsible for initiation of autophagy would affect autophagy induction by SRT1720. Also, LC3-II formation was reduced in SIRT1 and ATG7 knockout MEFs (Fig 3E). Therefore, SRT1720 increases the formation of the autophagy marker, LC3-II, through SIRT1 and ATG7. Then it was determined whether blocking autophagy induction by SRT1720 with 3-MA or ATG7 knockout cells could affect cell death. MDAMB-231 cells treated with either SRT1720 or 2.5 mM 3-MA resulted in a 65% and 18% decrease in cell viability, respectively. Treatment of wild-type MEFs with 5 µmol/L of SRT1720 resulted in a 22% decrease in cell viability, whereas, the number of ATG7 knockout cells decreased by 80% (Fig. 3G). Therefore, these results suggest that autophagy is increased during SRT1720 treatment due to cellular stress as a mechanism to promote cell survival. Mol Cancer Ther. 2015 Jan; 14(1): 183–192. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297239/ |
| In vivo activity: | In the present study, renal susceptibility to acute ischemia–reperfusion-induced injury in young and adult mice and the role of SIRT1 was examined in this age-dependent susceptibility. The SIRT1 activator SRT-1720 but not the vehicle significantly reduced BUN and creatinine levels in mice following I/R. The effect of SRT-1720 on the kidney was also supported by histological evaluation: the kidney injury score of SRT-treated mice was significantly lower than that of vehicle-treated mice (SRT 1.58±0.14 vs. vehicle 2.06±0.15, outer medulla; P<0.05) (Figure 4a–c). A higher cellular proliferation rate, as assessed by PCNA, was found 48h after I/R in the kidneys of young mice than in the kidneys of adult mice, and SRT-1720 treatment increased cellular proliferation in adult mice. The SIRT1 activator SRT-1720 reduced the expression of p53 in the kidney. In summary, the present data identify SIRT1 as a protective mediator in the kidneys of young mice following renal ischemia–reperfusion injury. The SIRT1 activator SRT-1720 protects against I/R injury by attenuating apoptosis and promoting regeneration, whereas an SIRT1 deficiency worsens kidney tissue injury following I/R. These studies suggest that SIRT1 is an important survival factor that may be a novel therapeutic target during ischemic episodes. Kidney Int. 2013 Mar;83(3):404-13. https://pubmed.ncbi.nlm.nih.gov/23302720/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 5.0 | 10.65 |
The following data is based on the product molecular weight 469.56 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.
| 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. Rowlands BD, Klugmann M, Rae CD. Acetate metabolism does not reflect astrocytic activity, contributes directly to GABA synthesis, and is increased by silent information regulator 1 activation. J Neurochem. 2017 Mar;140(6):903-918. doi: 10.1111/jnc.13916. Epub 2017 Jan 23. PMID: 27925207. 2. Liang D, Zhuo Y, Guo Z, He L, Wang X, He Y, Li L, Dai H. SIRT1/PGC-1 pathway activation triggers autophagy/mitophagy and attenuates oxidative damage in intestinal epithelial cells. Biochimie. 2020 Mar;170:10-20. doi: 10.1016/j.biochi.2019.12.001. Epub 2019 Dec 9. PMID: 31830513. 3. Fan H, Yang HC, You L, Wang YY, He WJ, Hao CM. The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/reperfusion-induced acute kidney injury. Kidney Int. 2013 Mar;83(3):404-13. doi: 10.1038/ki.2012.394. Epub 2013 Jan 9. PMID: 23302720. 4. Yu L, Liu X, Yuan Z, Li X, Yang H, Yuan Z, Sun L, Zhang L, Jiang Z. SRT1720 Alleviates ANIT-Induced Cholestasis in a Mouse Model. Front Pharmacol. 2017 May 11;8:256. doi: 10.3389/fphar.2017.00256. PMID: 28553227; PMCID: PMC5425580. |
| In vitro protocol: | 1. Rowlands BD, Klugmann M, Rae CD. Acetate metabolism does not reflect astrocytic activity, contributes directly to GABA synthesis, and is increased by silent information regulator 1 activation. J Neurochem. 2017 Mar;140(6):903-918. doi: 10.1111/jnc.13916. Epub 2017 Jan 23. PMID: 27925207. 2. Liang D, Zhuo Y, Guo Z, He L, Wang X, He Y, Li L, Dai H. SIRT1/PGC-1 pathway activation triggers autophagy/mitophagy and attenuates oxidative damage in intestinal epithelial cells. Biochimie. 2020 Mar;170:10-20. doi: 10.1016/j.biochi.2019.12.001. Epub 2019 Dec 9. PMID: 31830513 |
| In vivo protocol: | 1. Fan H, Yang HC, You L, Wang YY, He WJ, Hao CM. The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/reperfusion-induced acute kidney injury. Kidney Int. 2013 Mar;83(3):404-13. doi: 10.1038/ki.2012.394. Epub 2013 Jan 9. PMID: 23302720. |
1: Gueguen C, Palmier B, Plotkine M, Marchand-Leroux C, Bessson VC. Neurological and Histological Consequences Induced by In Vivo Cerebral Oxidative Stress: Evidence for Beneficial Effects of SRT1720, a Sirtuin 1 Activator, and Sirtuin 1-Mediated Neuroprotective Effects of Poly(ADP-ribose) Polymerase Inhibition. PLoS One. 2014 Feb 21;9(2):e87367. doi: 10.1371/journal.pone.0087367. eCollection 2014. PubMed PMID: 24586272; PubMed Central PMCID: PMC3931616.
2: Mitchell SJ, Martin-Montalvo A, Mercken EM, Palacios HH, Ward TM, Abulwerdi G, Minor RK, Vlasuk GP, Ellis JL, Sinclair DA, Dawson J, Allison DB, Zhang Y, Becker KG, Bernier M, de Cabo R. The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet. Cell Rep. 2014 Feb 25. pii: S2211-1247(14)00065-5. doi: 10.1016/j.celrep.2014.01.031. [Epub ahead of print] PubMed PMID: 24582957.
3: Nguyen GT, Schaefer S, Gertz M, Weyand M, Steegborn C. Structures of human sirtuin 3 complexes with ADP-ribose and with carba-NAD+ and SRT1720: binding details and inhibition mechanism. Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1423-32. doi: 10.1107/S0907444913015448. Epub 2013 Jul 17. PubMed PMID: 23897466.
4: Matsuya Y, Kobayashi Y, Uchida S, Itoh Y, Sawada H, Suzuki T, Miyata N, Sugimoto K, Toyooka N. Search for a novel SIRT1 activator: structural modification of SRT1720 and biological evaluation. Bioorg Med Chem Lett. 2013 Sep 1;23(17):4907-10. doi: 10.1016/j.bmcl.2013.06.070. Epub 2013 Jul 3. PubMed PMID: 23876989.
5: Ichikawa T, Hayashi R, Suzuki K, Imanishi S, Kambara K, Okazawa S, Inomata M, Yamada T, Yamazaki Y, Koshimizu Y, Miwa T, Matsui S, Usui I, Urakaze M, Matsuya Y, Sasahara M, Tobe K. Sirtuin 1 activator SRT1720 suppresses inflammation in an ovalbumin-induced mouse model of asthma. Respirology. 2013 Feb;18(2):332-9. doi: 10.1111/j.1440-1843.2012.02284.x. PubMed PMID: 23062010.
6: Suzuki K, Hayashi R, Ichikawa T, Imanishi S, Yamada T, Inomata M, Miwa T, Matsui S, Usui I, Urakaze M, Matsuya Y, Ogawa H, Sakurai H, Saiki I, Tobe K. SRT1720, a SIRT1 activator, promotes tumor cell migration, and lung metastasis of breast cancer in mice. Oncol Rep. 2012 Jun;27(6):1726-32. doi: 10.3892/or.2012.1750. Epub 2012 Mar 27. PubMed PMID: 22470132.
7: Minor RK, Baur JA, Gomes AP, Ward TM, Csiszar A, Mercken EM, Abdelmohsen K, Shin YK, Canto C, Scheibye-Knudsen M, Krawczyk M, Irusta PM, MartÃn-Montalvo A, Hubbard BP, Zhang Y, Lehrmann E, White AA, Price NL, Swindell WR, Pearson KJ, Becker KG, Bohr VA, Gorospe M, Egan JM, Talan MI, Auwerx J, Westphal CH, Ellis JL, Ungvari Z, Vlasuk GP, Elliott PJ, Sinclair DA, de Cabo R. SRT1720 improves survival and healthspan of obese mice. Sci Rep. 2011;1:70. doi: 10.1038/srep00070. Epub 2011 Aug 18. Erratum in: Sci Rep. 2013;3():1131. PubMed PMID: 22355589; PubMed Central PMCID: PMC3216557.
8: Chauhan D, Bandi M, Singh AV, Ray A, Raje N, Richardson P, Anderson KC. Preclinical evaluation of a novel SIRT1 modulator SRT1720 in multiple myeloma cells. Br J Haematol. 2011 Dec;155(5):588-98. doi: 10.1111/j.1365-2141.2011.08888.x. Epub 2011 Sep 26. PubMed PMID: 21950728.
9: Huber JL, McBurney MW, Distefano PS, McDonagh T. SIRT1-independent mechanisms of the putative sirtuin enzyme activators SRT1720 and SRT2183. Future Med Chem. 2010 Dec;2(12):1751-9. doi: 10.4155/fmc.10.257. PubMed PMID: 21428798.
10: Zarse K, Schmeisser S, Birringer M, Falk E, Schmoll D, Ristow M. Differential effects of resveratrol and SRT1720 on lifespan of adult Caenorhabditis elegans. Horm Metab Res. 2010 Nov;42(12):837-9. doi: 10.1055/s-0030-1265225. Epub 2010 Oct 5. PubMed PMID: 20925017.
11: Funk JA, Odejinmi S, Schnellmann RG. SRT1720 induces mitochondrial biogenesis and rescues mitochondrial function after oxidant injury in renal proximal tubule cells. J Pharmacol Exp Ther. 2010 May;333(2):593-601. doi: 10.1124/jpet.109.161992. Epub 2010 Jan 26. PubMed PMID: 20103585; PubMed Central PMCID: PMC2872958.
12: Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, Garofalo RS, Griffith D, Griffor M, Loulakis P, Pabst B, Qiu X, Stockman B, Thanabal V, Varghese A, Ward J, Withka J, Ahn K. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem. 2010 Mar 12;285(11):8340-51. doi: 10.1074/jbc.M109.088682. Epub 2010 Jan 8. PubMed PMID: 20061378; PubMed Central PMCID: PMC2832984.
13: Yamazaki Y, Usui I, Kanatani Y, Matsuya Y, Tsuneyama K, Fujisaka S, Bukhari A, Suzuki H, Senda S, Imanishi S, Hirata K, Ishiki M, Hayashi R, Urakaze M, Nemoto H, Kobayashi M, Tobe K. Treatment with SRT1720, a SIRT1 activator, ameliorates fatty liver with reduced expression of lipogenic enzymes in MSG mice. Am J Physiol Endocrinol Metab. 2009 Nov;297(5):E1179-86. doi: 10.1152/ajpendo.90997.2008. Epub 2009 Sep 1. PubMed PMID: 19724016.
