| Bioactivity | ABT-546 (A-216546) is a potent, highly selective and active endothelin ETA receptor antagonist with a Ki of 0.46 nM for [125I]endothelin-1 binding to cloned human endothelin ETA. ABT-546 is >25,000-fold more selective for the ETA receptor than for the ETB receptor. ABT-546 blocks endothelin-1-induced arachidonic acid release and phosphatidylinositol hydrolysis with IC50 of 0.59 nM and 3 nM, respectively[1]. |
| Invitro | ABT-546 (A-216546) effectively inhibits specific I endothelin-1 binding to endothelin ETA receptor in membranes prepared from rat pituitary MMQ cells with an IC50 value of 0.56 nM. ABT-546 is much less effective in inhibiting specific [125I]endothelin-3 binding to endothelin ETB rceptor in membranes prepared from porcine cerebellum with an IC50 value of 16,700 nM. In membranes prepared from CHO cells stably transfected with the human endothelin ETA and ETB receptors, ABT-546 again effectively inhibits specific [125I]endothelin-1 binding to endothelin ETA receptor with an IC50 value of 0.49 nM, but is less effective in inhibiting specific [125I]endothelin-3 binding to endothelin ETB receptor with an IC50 value of 15,400 nM[1].In isolated vessels, ABT-546 inhibits endothelin ETA receptor-mediated endothelin-1-induced vasoconstriction, and endothelin ETB receptor-mediated sarafotoxin 6c-induces vasoconstriction with pA2 of 8.29 and 4.57, respectively[1]. |
| In Vivo | ABT-546 (A-216546; 0-100 mg/kg; oral administration; for 1 hour or 4 hours; male Sprague-Dawley rats) treatment dose-dependently blocks endothelin-1-induced pressor response in conscious rats[1]. Animal Model: |
| Name | ABT-546 |
| CAS | 212481-66-8 |
| Formula | C30H48N2O6 |
| Molar Mass | 532.71 |
| Transport | Room temperature in continental US; may vary elsewhere. |
| Storage | Please store the product under the recommended conditions in the Certificate of Analysis. |
| Reference | [1]. u-Wong JR, et al. Pharmacology of A-216546: a highly selective antagonist for endothelin ET(A) receptor. Eur J Pharmacol. 1999 Feb 5;366(2-3):189-201. |