AZD7545
AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2) with IC50 value of 6.4nM [1].
PDH catalyzes the decarboxylation of pyruvate, converting it to acetyl-CoA. This enzyme is regulated by PDH kinases. The inhibitor of PDHK is developed for the treatment of type 2 diabetes. AZD7545 is a selective inhibitor of PDHK2. It inhibits PDHK1 and PDHK2 with IC50 values of 36.8nM and 6.4nM, respectively. Besides that, AZD7545 increases PDH activity with EC50 value of 5.2nM when using recombinant human PDHK2. In vivo studies show that administration of AZD7545 significantly activates PDH activity in liver and partially activates PDH activity in skeletal muscle and heart. In Zucker (fa/fa) rats, AZD7545 at dose of 10 mg/kg increases muscle PDH from 61% to 97% active and liver PDH from 33.5% to 72.8% [1, 2].
References:
[1] Morrell J A, Orme J, Butlin R J, et al. AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2. Biochemical society transactions, 2003, 31(6): 1168-1170.
[2] Mayers R M, Butlin R J, Kilgour E, et al. 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. Biochemical Society Transactions, 2003, 31(6): 1165-1167.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 478.87 |
| Cas No. | 252017-04-2 |
| Formula | C19H18ClF3N2O5S |
| Solubility | ≥21.85 mg/mL in DMSO; insoluble in H2O; ≥15.63 mg/mL in EtOH with ultrasonic |
| Chemical Name | 4-[3-chloro-4-[[(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl]amino]phenyl]sulfonyl-N,N-dimethylbenzamide |
| SDF | Download SDF |
| Canonical SMILES | CC(C(=O)NC1=C(C=C(C=C1)S(=O)(=O)C2=CC=C(C=C2)C(=O)N(C)C)Cl)(C(F)(F)F)O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Kinase experiment [1]: | |
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Inhibition of PDHK isoenzyme assay |
The incorporation of [33P]ATP into the E1 subunit of PDH is measured at 30°C in Mops-K+ buffer in the presence of 100 μM ATP and E2 subunit. Recombinant human proteins are used throughout. Compounds J, K and L are from the same chemical series as AZD7545. IC50 values are means±.E.M. with the number of observations given in parentheses. |
| Animal experiment [2]: | |
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Animal models |
Wistar rats model; obese Zucker (fa/fa) rats model |
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Dosage form |
3, 10, and 30 mg/kg twice daily；oral administration for 7 days |
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Applications |
AZD7545 more effectively increased PDH activity in liver than in skeletal muscle and heart in wistar rats model. Moreover, AZD7545 significantly elevated pyruvate dehydrogenase (PDH) activity in vivo and markedly improved blood glucose control in obese (fa/fa) Zucker rats. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1. Morrell, J. A., Orme, J., Butlin, R. J., Roche, T. E., Mayers, R. M. and Kilgour, E. (2003) AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2. Biochem Soc Trans. 31, 1168-1170 2. Mayers, R. M., Butlin, R. J., Kilgour, E., Leighton, B., Martin, D., Myatt, J., Orme, J. P. and Holloway, B. R. (2003) 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. 31, 1165-1167 | |
| Description | AZD7545 is a potent inhibitor of PDHK with IC50 values of 36.8 nM and 6.4 nM for PDHK1 and PDHK2, respectively. | |||||
| Targets | PDHK2 | PDHK1 | ||||
| IC50 | 6.4 nM | 36.8 nM | ||||
Quality Control & MSDS
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Chemical structure
