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MedKoo Cat#: 401018 | Name: A-769662
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

A-769662 is a potent, reversible AMP-activated protein kinase (AMPK) activator with an EC50 of 0.8 μM.A-769662 displays selectivity towards β1 subunit-containing heterotrimers. Unlike other pharmacological activators, it directly activates native rat AMPK by mimicking both effects of AMP, i.e. allosteric activation and inhibition of dephosphorylation. It was found that it has no effect on the isolated alpha subunit kinase domain, with or without the associated autoinhibitory domain, or on interaction of glycogen with the beta subunit glycogen-binding domain. Although it mimics actions of AMP, it has no effect on binding of AMP to the isolated Bateman domains of the gamma subunit. The addition of A-769662 to mouse embryonic fibroblasts or primary mouse hepatocytes stimulates phosphorylation of acetyl-CoA carboxylase (ACC), effects that are completely abolished in AMPK-alpha1(-/-)alpha2(-/-) cells but not in TAK1(-/-) mouse embryonic fibroblasts. Phosphorylation of AMPK and ACC in response to A-769662 is also abolished in isolated mouse skeletal muscle lacking LKB1, a major upstream kinase for AMPK in this tissue. However, in HeLa cells, which lack LKB1 but express the alternate upstream kinase calmodulin-dependent protein kinase kinase-beta, phosphorylation of AMPK and ACC in response to A-769662 still occurs. These results show that in intact cells, the effects of A-769662 are independent of the upstream kinase utilized.

Chemical Structure

A-769662
A-769662
CAS#844499-71-4

Theoretical Analysis

MedKoo Cat#: 401018

Name: A-769662

CAS#: 844499-71-4

Chemical Formula: C20H12N2O3S

Exact Mass: 360.0569

Molecular Weight: 360.39

Elemental Analysis: C, 66.65; H, 3.36; N, 7.77; O, 13.32; S, 8.90

Price and Availability

Size Price Availability Quantity
50mg USD 350.00 2 Weeks
100mg USD 550.00 2 Weeks
250mg USD 950.00 2 Weeks
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Related CAS #
No Data
Synonym
A769662; A 769662; A-769662
IUPAC/Chemical Name
4-hydroxy-3-(2'-hydroxy-[1,1'-biphenyl]-4-yl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carbonitrile
InChi Key
CTESJDQKVOEUOY-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H12N2O3S/c21-9-14-18(24)17-15(10-26-20(17)22-19(14)25)12-7-5-11(6-8-12)13-3-1-2-4-16(13)23/h1-8,10,23H,(H2,22,24,25)
SMILES Code
N#CC1=C(O)C(C(C2=CC=C(C3=CC=CC=C3O)C=C2)=CS4)=C4NC1=O
Appearance
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
A-769662 is a new activator of AMP-activated protein kinase (AMPK). Unlike other pharmacological activators, it directly activates native rat AMPK by mimicking both effects of AMP, i.e. allosteric activation and inhibition of dephosphorylation. It was found that it has no effect on the isolated alpha subunit kinase domain, with or without the associated autoinhibitory domain, or on interaction of glycogen with the beta subunit glycogen-binding domain. Although it mimics actions of AMP, it has no effect on binding of AMP to the isolated Bateman domains of the gamma subunit. The addition of A-769662 to mouse embryonic fibroblasts or primary mouse hepatocytes stimulates phosphorylation of acetyl-CoA carboxylase (ACC), effects that are completely abolished in AMPK-alpha1(-/-)alpha2(-/-) cells but not in TAK1(-/-) mouse embryonic fibroblasts. Phosphorylation of AMPK and ACC in response to A-769662 is also abolished in isolated mouse skeletal muscle lacking LKB1, a major upstream kinase for AMPK in this tissue. However, in HeLa cells, which lack LKB1 but express the alternate upstream kinase calmodulin-dependent protein kinase kinase-beta, phosphorylation of AMPK and ACC in response to A-769662 still occurs. These results show that in intact cells, the effects of A-769662 are independent of the upstream kinase utilized.  (see: Göransson O, McBride A, Hawley SA, Ross FA, Shpiro N, Foretz M, Viollet B, Hardie DG, Sakamoto K. Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J Biol Chem. 2007 Nov 9;282(45):32549-60. http://www.ncbi.nlm.nih.gov/pubmed/17855357)    

Preparing Stock Solutions

The following data is based on the product molecular weight 360.39 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
1: Kopietz F, Alshuweishi Y, Bijland S, Alghamdi F, Degerman E, Sakamoto K, Salt IP, Göransson O. A-769662 inhibits adipocyte glucose uptake in an AMPK- independent manner. Biochem J. 2021 Feb 12;478(3):633-646. doi: 10.1042/BCJ20200659. PMID: 33493298. 2: Abdallah BM, Alzahrani AM. A-769662 stimulates the differentiation of bone marrow-derived mesenchymal stem cells into osteoblasts via AMP-activated protein kinase-dependent mechanism. J Appl Biomed. 2021 Sep;19(3):159-169. doi: 10.32725/jab.2021.016. Epub 2021 Jul 1. PMID: 34907759. 3: Rameshrad M, Soraya H, Maleki-Dizaji N, Vaez H, Garjani A. A-769662, a direct AMPK activator, attenuates lipopolysaccharide-induced acute heart and lung inflammation in rats. Mol Med Rep. 2016 Mar;13(3):2843-9. doi: 10.3892/mmr.2016.4821. Epub 2016 Jan 28. PMID: 26820069. 4: Hu Y, Bai J, Xia Y, Lin Y, Ma L, Xu X, Ding Y, Chen L. Increasing SnRK1 activity with the AMPK activator A-769662 accelerates seed germination in rice. Plant Physiol Biochem. 2022 Aug 15;185:155-166. doi: 10.1016/j.plaphy.2022.06.005. Epub 2022 Jun 7. PMID: 35696890. 5: Rameshrad M, Maleki-Dizaji N, Soraya H, Toutounchi NS, Barzegari A, Garjani A. Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue. Iran J Basic Med Sci. 2016 Dec;19(12):1308-1317. doi: 10.22038/ijbms.2016.7917. PMID: 28096963; PMCID: PMC5220236. 6: Zhu Y, Zhou J, Ao R, Yu B. A-769662 protects osteoblasts from hydrogen dioxide-induced apoptosis through activating of AMP-activated protein kinase (AMPK). Int J Mol Sci. 2014 Jun 23;15(6):11190-203. doi: 10.3390/ijms150611190. PMID: 24960362; PMCID: PMC4100207. 7: Timmermans AD, Balteau M, Gélinas R, Renguet E, Ginion A, de Meester C, Sakamoto K, Balligand JL, Bontemps F, Vanoverschelde JL, Horman S, Beauloye C, Bertrand L. A-769662 potentiates the effect of other AMP-activated protein kinase activators on cardiac glucose uptake. Am J Physiol Heart Circ Physiol. 2014 Jun 15;306(12):H1619-30. doi: 10.1152/ajpheart.00965.2013. Epub 2014 Apr 18. PMID: 24748590. 8: Kopietz F, Berggreen C, Larsson S, Säll J, Ekelund M, Sakamoto K, Degerman E, Holm C, Göransson O. AMPK activation by A-769662 and 991 does not affect catecholamine-induced lipolysis in human adipocytes. Am J Physiol Endocrinol Metab. 2018 Nov 1;315(5):E1075-E1085. doi: 10.1152/ajpendo.00110.2018. Epub 2018 Sep 25. PMID: 30253109. 9: Guma M, Wang Y, Viollet B, Liu-Bryan R. AMPK Activation by A-769662 Controls IL-6 Expression in Inflammatory Arthritis. PLoS One. 2015 Oct 16;10(10):e0140452. doi: 10.1371/journal.pone.0140452. PMID: 26474486; PMCID: PMC4608670. 10: Zhou Y, Wang D, Zhu Q, Gao X, Yang S, Xu A, Wu D. Inhibitory effects of A-769662, a novel activator of AMP-activated protein kinase, on 3T3-L1 adipogenesis. Biol Pharm Bull. 2009 Jun;32(6):993-8. doi: 10.1248/bpb.32.993. PMID: 19483304. 11: Treebak JT, Birk JB, Hansen BF, Olsen GS, Wojtaszewski JF. A-769662 activates AMPK beta1-containing complexes but induces glucose uptake through a PI3-kinase-dependent pathway in mouse skeletal muscle. Am J Physiol Cell Physiol. 2009 Oct;297(4):C1041-52. doi: 10.1152/ajpcell.00051.2009. Epub 2009 Aug 5. PMID: 19657063. 12: Göransson O, McBride A, Hawley SA, Ross FA, Shpiro N, Foretz M, Viollet B, Hardie DG, Sakamoto K. Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J Biol Chem. 2007 Nov 9;282(45):32549-60. doi: 10.1074/jbc.M706536200. Epub 2007 Sep 12. PMID: 17855357; PMCID: PMC2156105. 13: Scott JW, Ling N, Issa SM, Dite TA, O'Brien MT, Chen ZP, Galic S, Langendorf CG, Steinberg GR, Kemp BE, Oakhill JS. Small molecule drug A-769662 and AMP synergistically activate naive AMPK independent of upstream kinase signaling. Chem Biol. 2014 May 22;21(5):619-27. doi: 10.1016/j.chembiol.2014.03.006. Epub 2014 Apr 17. PMID: 24746562. 14: Benziane B, Björnholm M, Lantier L, Viollet B, Zierath JR, Chibalin AV. AMP- activated protein kinase activator A-769662 is an inhibitor of the Na(+)-K(+)-ATPase. Am J Physiol Cell Physiol. 2009 Dec;297(6):C1554-66. doi: 10.1152/ajpcell.00010.2009. Epub 2009 Oct 14. PMID: 19828836. 15: Sanders MJ, Ali ZS, Hegarty BD, Heath R, Snowden MA, Carling D. Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family. J Biol Chem. 2007 Nov 9;282(45):32539-48. doi: 10.1074/jbc.M706543200. Epub 2007 Aug 29. PMID: 17728241. 16: Vlachaki Walker JM, Robb JL, Cruz AM, Malhi A, Weightman Potter PG, Ashford MLJ, McCrimmon RJ, Ellacott KLJ, Beall C. AMP-activated protein kinase (AMPK) activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner. Diabetes Obes Metab. 2017 Jul;19(7):997-1005. doi: 10.1111/dom.12912. Epub 2017 Apr 21. PMID: 28211632. 17: Madhavi YV, Gaikwad N, Yerra VG, Kalvala AK, Nanduri S, Kumar A. Targeting AMPK in Diabetes and Diabetic Complications: Energy Homeostasis, Autophagy and Mitochondrial Health. Curr Med Chem. 2019;26(27):5207-5229. doi: 10.2174/0929867325666180406120051. PMID: 29623826. 18: Huang Y, Smith CA, Chen G, Sharma B, Miner AS, Barbee RW, Ratz PH. The AMP- Dependent Protein Kinase (AMPK) Activator A-769662 Causes Arterial Relaxation by Reducing Cytosolic Free Calcium Independently of an Increase in AMPK Phosphorylation. Front Pharmacol. 2017 Oct 18;8:756. doi: 10.3389/fphar.2017.00756. PMID: 29093683; PMCID: PMC5651270. 19: Dai X, Bu X, Gao Y, Guo J, Hu J, Jiang C, Zhang Z, Xu K, Duan J, He S, Zhang J, Wan L, Liu T, Zhou X, Hung MC, Freeman GJ, Wei W. Energy status dictates PD-L1 protein abundance and anti-tumor immunity to enable checkpoint blockade. Mol Cell. 2021 Jun 3;81(11):2317-2331.e6. doi: 10.1016/j.molcel.2021.03.037. Epub 2021 Apr 27. PMID: 33909988; PMCID: PMC8178223. 20: Han Y, Hu Z, Cui A, Liu Z, Ma F, Xue Y, Liu Y, Zhang F, Zhao Z, Yu Y, Gao J, Wei C, Li J, Fang J, Li J, Fan JG, Song BL, Li Y. Post-translational regulation of lipogenesis via AMPK-dependent phosphorylation of insulin-induced gene. Nat Commun. 2019 Feb 7;10(1):623. doi: 10.1038/s41467-019-08585-4. PMID: 30733434; PMCID: PMC6367348.