Synonym
AZD7545; AZD-7545; AZD 7545.
IUPAC/Chemical Name
4-[3-chloro-4-[[(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl]amino]phenyl]sulfonyl-N,N-dimethylbenzamide
InChi Key
DTDZLJHKVNTQGZ-GOSISDBHSA-N
InChi Code
InChI=1S/C19H18ClF3N2O5S/c1-18(28,19(21,22)23)17(27)24-15-9-8-13(10-14(15)20)31(29,30)12-6-4-11(5-7-12)16(26)25(2)3/h4-10,28H,1-3H3,(H,24,27)/t18-/m1/s1
SMILES Code
O=C(N(C)C)C1=CC=C(S(=O)(C2=CC=C(NC([C@@](C)(O)C(F)(F)F)=O)C(Cl)=C2)=O)C=C1
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
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
Preparing Stock Solutions
The following data is based on the
product
molecular weight
478.87
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 |
1: Kato M, Li J, Chuang JL, Chuang DT. Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol. Structure. 2007 Aug;15(8):992-1004. PubMed PMID: 17683942; PubMed Central PMCID: PMC2871385.
2: Tuganova A, Klyuyeva A, Popov KM. Recognition of the inner lipoyl-bearing domain of dihydrolipoyl transacetylase and of the blood glucose-lowering compound AZD7545 by pyruvate dehydrogenase kinase 2. Biochemistry. 2007 Jul 24;46(29):8592-602. PubMed PMID: 17602666; PubMed Central PMCID: PMC2136408.
3: Mayers RM, Butlin RJ, Kilgour E, Leighton B, Martin D, Myatt J, Orme JP, Holloway BR. AZD7545, a novel inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2), activates pyruvate dehydrogenase in vivo and improves blood glucose control in obese (fa/fa) Zucker rats. Biochem Soc Trans. 2003 Dec;31(Pt 6):1165-7. Review. PubMed PMID: 14641018.
4: Morrell JA, Orme J, Butlin RJ, Roche TE, Mayers RM, Kilgour E. AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2. Biochem Soc Trans. 2003 Dec;31(Pt 6):1168-70. PubMed PMID: 14641019.
5: Makita N, Ishiguro J, Suzuki K, Nara F. Dichloroacetate induces regulatory T-cell differentiation and suppresses Th17-cell differentiation by pyruvate dehydrogenase kinase-independent mechanism. J Pharm Pharmacol. 2017 Jan;69(1):43-51. doi: 10.1111/jphp.12655. PubMed PMID: 27757958.
6: Jones HB, Reens J, Johnson E, Brocklehurst S, Slater I. Myocardial steatosis and necrosis in atria and ventricles of rats given pyruvate dehydrogenase kinase inhibitors. Toxicol Pathol. 2014 Dec;42(8):1250-66. doi: 10.1177/0192623314530195. PubMed PMID: 24742628.
7: Hiromasa Y, Yan X, Roche TE. Specific ion influences on self-association of pyruvate dehydrogenase kinase isoform 2 (PDHK2), binding of PDHK2 to the L2 lipoyl domain, and effects of the lipoyl group-binding site inhibitor, Nov3r. Biochemistry. 2008 Feb 26;47(8):2312-24. doi: 10.1021/bi7014772. PubMed PMID: 18220415.
8: Li J, Kato M, Chuang DT. Pivotal role of the C-terminal DW-motif in mediating inhibition of pyruvate dehydrogenase kinase 2 by dichloroacetate. J Biol Chem. 2009 Dec 4;284(49):34458-67. doi: 10.1074/jbc.M109.065557. PubMed PMID: 19833728; PubMed Central PMCID: PMC2797213.
9: Wynn RM, Kato M, Chuang JL, Tso SC, Li J, Chuang DT. Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity. J Biol Chem. 2008 Sep 12;283(37):25305-15. doi: 10.1074/jbc.M802249200. PubMed PMID: 18658136; PubMed Central PMCID: PMC2533096.
10: Mayers RM, Leighton B, Kilgour E. PDH kinase inhibitors: a novel therapy for Type II diabetes? Biochem Soc Trans. 2005 Apr;33(Pt 2):367-70. Review. PubMed PMID: 15787608.
