WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H510273
CAS#: 1469924-27-3
Description: Atglistatin is a potent and selective adipose triglyceride lipase (ATGL) inhibitor. ATGL is rate limiting in the mobilization of fatty acids from cellular triglyceride stores. This central role in lipolysis marks ATGL as an interesting pharmacological target as deregulated fatty acid metabolism is closely linked to dyslipidemic and metabolic disorders. Atglistatin is selective for ATGL and reduces fatty acid mobilization in vitro and in vivo.
Hodoodo Cat#: H510273
Name: Atglistatin
CAS#: 1469924-27-3
Chemical Formula: C17H21N3O
Exact Mass: 283.17
Molecular Weight: 283.370
Elemental Analysis: C, 72.06; H, 7.47; N, 14.83; O, 5.65
Synonym: Atglistatin
IUPAC/Chemical Name: 3-(4'-(dimethylamino)-[1,1'-biphenyl]-3-yl)-1,1-dimethylurea
InChi Key: AWOPBSAJHCUSAS-UHFFFAOYSA-N
InChi Code: InChI=1S/C17H21N3O/c1-19(2)16-10-8-13(9-11-16)14-6-5-7-15(12-14)18-17(21)20(3)4/h5-12H,1-4H3,(H,18,21)
SMILES Code: CN(C1=CC=C(C=C1)C2=CC(NC(N(C)C)=O)=CC=C2)C
Appearance: white to off-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: License information: This product is produced and sold under the license of University of Graz / Graz University of Technology.
| Biological target: | Atglistatin is a selective adipose triglyceride lipase (ATGL) inhibitor which inhibits lipolysis with an IC50 of 0.7 μM in vitro. |
| In vitro activity: | As previous publications demonstrated that inhibition of ATGL activity by Atglistatin© affects tumor cell proliferation, this study undertook a further set of experiments. To investigate the effect of lipase inhibition on cancer cell proliferation in more detail, this study specifically inhibited ATGL (Atglistatin©, AI), HSL (Hi-76-0079, HI), and MGL (JZL184, MI) activities in five different cancer cell lines. Atglistatin© treatment significantly reduced proliferation of all cancer cells this study examined (Fig. 4A–B, Fig. S4A–C), whereas inhibitors for HSL and MGL remained without any effect (Fig. 4A–B, Fig. S4A–C). Reference: Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Sep; 1865(9): 158737. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397471/ |
| In vivo activity: | Three weeks after surgery, atglistatin-treated mice showed significantly better cardiac function compared with vehicle-treated mice in a number of parameters (Table 1 and Fig. 1, C and D). In addition, mice treated with atglistatin also had significantly reduced cardiac hypertrophy, as evidenced by the significant decrease in LV mass (Fig. 1E). Moreover, atglistatin treatment lowered pulmonary signs of HF, as indicated by a significantly lower lung weight (Fig. 1F). Reference: Am J Physiol Heart Circ Physiol. 2018 Oct 1;315(4):H879-H884. https://pubmed.ncbi.nlm.nih.gov/29932770/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 52.5 | 185.27 | |
| DMSO:PBS (pH 7.2) (1:1) | 0.5 | 1.76 | |
| DMF | 5.0 | 17.64 | |
| Ethanol | 3.5 | 12.35 |
The following data is based on the product molecular weight 283.37 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. Xie H, Heier C, Kien B, Vesely PW, Tang Z, Sexl V, Schoiswohl G, Strießnig-Bina I, Hoefler G, Zechner R, Schweiger M. Adipose triglyceride lipase activity regulates cancer cell proliferation via AMP-kinase and mTOR signaling. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Sep;1865(9):158737. doi: 10.1016/j.bbalip.2020.158737. Epub 2020 May 11. PMID: 32404277; PMCID: PMC7397471. 2. MacPherson RE, Dragos SM, Ramos S, Sutton C, Frendo-Cumbo S, Castellani L, Watt MJ, Perry CG, Mutch DM, Wright DC. Reduced ATGL-mediated lipolysis attenuates β-adrenergic-induced AMPK signaling, but not the induction of PKA-targeted genes, in adipocytes and adipose tissue. Am J Physiol Cell Physiol. 2016 Aug 1;311(2):C269-76. doi: 10.1152/ajpcell.00126.2016. Epub 2016 Jun 29. PMID: 27357546; PMCID: PMC5129771. 3. Parajuli N, Takahara S, Matsumura N, Kim TT, Ferdaoussi M, Migglautsch AK, Zechner R, Breinbauer R, Kershaw EE, Dyck JRB. Atglistatin ameliorates functional decline in heart failure via adipocyte-specific inhibition of adipose triglyceride lipase. Am J Physiol Heart Circ Physiol. 2018 Oct 1;315(4):H879-H884. doi: 10.1152/ajpheart.00308.2018. Epub 2018 Jun 22. PMID: 29932770. 4. Schweiger M, Romauch M, Schreiber R, Grabner GF, Hütter S, Kotzbeck P, Benedikt P, Eichmann TO, Yamada S, Knittelfelder O, Diwoky C, Doler C, Mayer N, De Cecco W, Breinbauer R, Zimmermann R, Zechner R. Pharmacological inhibition of adipose triglyceride lipase corrects high-fat diet-induced insulin resistance and hepatosteatosis in mice. Nat Commun. 2017 Mar 22;8:14859. doi: 10.1038/ncomms14859. Erratum in: Nat Commun. 2017 Apr 25;8:15490. PMID: 28327588; PMCID: PMC5364409. |
| In vitro protocol: | 1. Xie H, Heier C, Kien B, Vesely PW, Tang Z, Sexl V, Schoiswohl G, Strießnig-Bina I, Hoefler G, Zechner R, Schweiger M. Adipose triglyceride lipase activity regulates cancer cell proliferation via AMP-kinase and mTOR signaling. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Sep;1865(9):158737. doi: 10.1016/j.bbalip.2020.158737. Epub 2020 May 11. PMID: 32404277; PMCID: PMC7397471. 2. MacPherson RE, Dragos SM, Ramos S, Sutton C, Frendo-Cumbo S, Castellani L, Watt MJ, Perry CG, Mutch DM, Wright DC. Reduced ATGL-mediated lipolysis attenuates β-adrenergic-induced AMPK signaling, but not the induction of PKA-targeted genes, in adipocytes and adipose tissue. Am J Physiol Cell Physiol. 2016 Aug 1;311(2):C269-76. doi: 10.1152/ajpcell.00126.2016. Epub 2016 Jun 29. PMID: 27357546; PMCID: PMC5129771. |
| In vivo protocol: | 1. Parajuli N, Takahara S, Matsumura N, Kim TT, Ferdaoussi M, Migglautsch AK, Zechner R, Breinbauer R, Kershaw EE, Dyck JRB. Atglistatin ameliorates functional decline in heart failure via adipocyte-specific inhibition of adipose triglyceride lipase. Am J Physiol Heart Circ Physiol. 2018 Oct 1;315(4):H879-H884. doi: 10.1152/ajpheart.00308.2018. Epub 2018 Jun 22. PMID: 29932770. 2. Schweiger M, Romauch M, Schreiber R, Grabner GF, Hütter S, Kotzbeck P, Benedikt P, Eichmann TO, Yamada S, Knittelfelder O, Diwoky C, Doler C, Mayer N, De Cecco W, Breinbauer R, Zimmermann R, Zechner R. Pharmacological inhibition of adipose triglyceride lipase corrects high-fat diet-induced insulin resistance and hepatosteatosis in mice. Nat Commun. 2017 Mar 22;8:14859. doi: 10.1038/ncomms14859. Erratum in: Nat Commun. 2017 Apr 25;8:15490. PMID: 28327588; PMCID: PMC5364409. |
1: Bottermann K, Granade ME, Oenarto V, Fischer JW, Harris TE. Atglistatin Pretreatment Preserves Remote Myocardium Function Following Myocardial Infarction. J Cardiovasc Pharmacol Ther. 2021 May;26(3):289-297. doi: 10.1177/1074248420971113. Epub 2020 Nov 5. PMID: 33150796.
2: Thiele A, Luettges K, Ritter D, Beyhoff N, Smeir E, Grune J, Steinhoff JS, Schupp M, Klopfleisch R, Rothe M, Wilck N, Bartolomaeus H, Migglautsch AK, Breinbauer R, Kershaw EE, Grabner GF, Zechner R, Kintscher U, Foryst-Ludwig A. Pharmacological inhibition of adipose tissue adipose triglyceride lipase by Atglistatin prevents catecholamine-induced myocardial damage. Cardiovasc Res. 2022 Aug 24;118(11):2488-2505. doi: 10.1093/cvr/cvab182. Erratum in: Cardiovasc Res. 2022 May 25;: PMID: 34061169; PMCID: PMC9890462.
3: Cerk IK, Wechselberger L, Oberer M. Adipose Triglyceride Lipase Regulation: An Overview. Curr Protein Pept Sci. 2018;19(2):221-233. doi: 10.2174/1389203718666170918160110. PMID: 28925902; PMCID: PMC7613786.
4: Roy PP, D'Souza K, Cuperlovic-Culf M, Kienesberger PC, Touaibia M. New Atglistatin closely related analogues: Synthesis and structure-activity relationship towards adipose triglyceride lipase inhibition. Eur J Med Chem. 2016 Aug 8;118:290-8. doi: 10.1016/j.ejmech.2016.04.021. Epub 2016 Apr 10. PMID: 27155760.
5: Parajuli N, Takahara S, Matsumura N, Kim TT, Ferdaoussi M, Migglautsch AK, Zechner R, Breinbauer R, Kershaw EE, Dyck JRB. Atglistatin ameliorates functional decline in heart failure via adipocyte-specific inhibition of adipose triglyceride lipase. Am J Physiol Heart Circ Physiol. 2018 Oct 1;315(4):H879-H884. doi: 10.1152/ajpheart.00308.2018. Epub 2018 Jun 22. PMID: 29932770.
6: Jin J, Huang S, Wang L, Leng Y, Lu W. Design and synthesis of Atglistatin derivatives as adipose triglyceride lipase inhibitors. Chem Biol Drug Des. 2017 Dec;90(6):1122-1133. doi: 10.1111/cbdd.13029. Epub 2017 Jun 26. PMID: 28548386.
7: Fang F, Goldstein JL, Shi X, Liang G, Brown MS. Unexpected role for IGF-1 in starvation: Maintenance of blood glucose. Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2208855119. doi: 10.1073/pnas.2208855119. Epub 2022 Aug 1. PMID: 35914126; PMCID: PMC9371671.
8: Bottermann K, Kalfhues L, Nederlof R, Hemmers A, Leitner LM, Oenarto V, Nemmer J, Pfeffer M, Raje V, Deenen R, Petzsch P, Zabri H, Köhrer K, Reichert AS, Grandoch M, Fischer JW, Herebian D, Stegbauer J, Harris TE, Gödecke A. Cardiomyocyte p38 MAPKα suppresses a heart-adipose tissue-neutrophil crosstalk in heart failure development. Basic Res Cardiol. 2022 Oct 7;117(1):48. doi: 10.1007/s00395-022-00955-2. PMID: 36205817; PMCID: PMC9542472.
9: Corrigendum to: Pharmacological inhibition of adipose tissue Adipose Triglyceride Lipase (ATGL) by Atglistatin prevents catecholamine-induced myocardial damage. Cardiovasc Res. 2022 Aug 24;118(11):2560. doi: 10.1093/cvr/cvac047. Erratum for: Cardiovasc Res. 2022 Aug 24;118(11):2488-2505. PMID: 35639519; PMCID: PMC10144680.
10: Takahara S, Ferdaoussi M, Srnic N, Maayah ZH, Soni S, Migglautsch AK, Breinbauer R, Kershaw EE, Dyck JRB. Inhibition of ATGL in adipose tissue ameliorates isoproterenol-induced cardiac remodeling by reducing adipose tissue inflammation. Am J Physiol Heart Circ Physiol. 2021 Jan 1;320(1):H432-H446. doi: 10.1152/ajpheart.00737.2020. Epub 2020 Nov 13. PMID: 33185110; PMCID: PMC7847076.
11: Han SL, Liu Y, Limbu SM, Chen LQ, Zhang ML, Du ZY. The reduction of lipid- sourced energy production caused by ATGL inhibition cannot be compensated by activation of HSL, autophagy, and utilization of other nutrients in fish. Fish Physiol Biochem. 2021 Feb;47(1):173-188. doi: 10.1007/s10695-020-00904-7. Epub 2020 Nov 27. PMID: 33245450.
12: Lee SJ, Duncan DS, Echevarria FD, McLaughlin WM, Hatcher JB, Sappington RM. Pressure-Induced Alterations in PEDF and PEDF-R Expression: Implications for Neuroprotective Signaling in Glaucoma. J Clin Exp Ophthalmol. 2015 Oct;6(5):491. doi: 10.4172/2155-9570.1000491. Epub 2015 Oct 27. PMID: 26807306; PMCID: PMC4721587.
13: Tuohetahuntila M, Molenaar MR, Spee B, Brouwers JF, Houweling M, Vaandrager AB, Helms JB. ATGL and DGAT1 are involved in the turnover of newly synthesized triacylglycerols in hepatic stellate cells. J Lipid Res. 2016 Jul;57(7):1162-74. doi: 10.1194/jlr.M066415. Epub 2016 May 14. PMID: 27179362; PMCID: PMC4918846.
14: Taxiarchis A, Mahdessian H, Silveira A, Fisher RM, Van't Hooft FM. PNPLA2 influences secretion of triglyceride-rich lipoproteins by human hepatoma cells. J Lipid Res. 2019 Jun;60(6):1069-1077. doi: 10.1194/jlr.M090928. Epub 2019 Mar 27. PMID: 30918066; PMCID: PMC6547638.
15: Mayer N, Schweiger M, Fuchs E, Migglautsch AK, Doler C, Grabner GF, Romauch M, Melcher MC, Zechner R, Zimmermann R, Breinbauer R. Structure-activity relationship studies for the development of inhibitors of murine adipose triglyceride lipase (ATGL). Bioorg Med Chem. 2020 Aug 15;28(16):115610. doi: 10.1016/j.bmc.2020.115610. Epub 2020 Jul 4. PMID: 32690265.
16: Kintscher U, Foryst-Ludwig A, Haemmerle G, Zechner R. The Role of Adipose Triglyceride Lipase and Cytosolic Lipolysis in Cardiac Function and Heart Failure. Cell Rep Med. 2020 Mar 25;1(1):100001. doi: 10.1016/j.xcrm.2020.100001. PMID: 33205054; PMCID: PMC7659492.
17: Schreiber R, Xie H, Schweiger M. Of mice and men: The physiological role of adipose triglyceride lipase (ATGL). Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Jun;1864(6):880-899. doi: 10.1016/j.bbalip.2018.10.008. Epub 2018 Oct 25. PMID: 30367950; PMCID: PMC6439276.
18: Schweiger M, Romauch M, Schreiber R, Grabner GF, Hütter S, Kotzbeck P, Benedikt P, Eichmann TO, Yamada S, Knittelfelder O, Diwoky C, Doler C, Mayer N, De Cecco W, Breinbauer R, Zimmermann R, Zechner R. Pharmacological inhibition of adipose triglyceride lipase corrects high-fat diet-induced insulin resistance and hepatosteatosis in mice. Nat Commun. 2017 Mar 22;8:14859. doi: 10.1038/ncomms14859. Erratum in: Nat Commun. 2017 Apr 25;8:15490. PMID: 28327588; PMCID: PMC5364409.
19: Mayer N, Schweiger M, Romauch M, Grabner GF, Eichmann TO, Fuchs E, Ivkovic J, Heier C, Mrak I, Lass A, Höfler G, Fledelius C, Zechner R, Zimmermann R, Breinbauer R. Development of small-molecule inhibitors targeting adipose triglyceride lipase. Nat Chem Biol. 2013 Dec;9(12):785-7. doi: 10.1038/nchembio.1359. Epub 2013 Oct 6. PMID: 24096302; PMCID: PMC3829776.
20: Ho TC, Fan NW, Yeh SI, Chen SL, Tsao YP. The Therapeutic Effects of a PEDF- Derived Short Peptide on Murine Experimental Dry Eye Involves Suppression of MMP-9 and Inflammation. Transl Vis Sci Technol. 2022 Oct 3;11(10):12. doi: 10.1167/tvst.11.10.12. PMID: 36201200; PMCID: PMC9554226.
