ABT-546

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.

Product information

CAS Number: 212481-66-8

Molecular Weight: 532.71

Formula: C30H48N2O6

Chemical Name: (2S,3R,4S)-1-[(dibutylcarbamoyl)methyl]-2-(2,2-dimethylpentyl)-4-(7-methoxy-2H-1,3-benzodioxol-5-yl)pyrrolidine-3-carboxylic acid

Smiles: COC1=CC(=CC2OCOC=21)[C@H]1CN(CC(=O)N(CCCC)CCCC)[C@@H](CC(C)(C)CCC)[C@@H]1C(O)=O

InChiKey: OAEWNSKRLBVVBV-QSEAXJEQSA-N

InChi: InChI=1S/C30H48N2O6/c1-7-10-13-31(14-11-8-2)26(33)19-32-18-22(21-15-24(36-6)28-25(16-21)37-20-38-28)27(29(34)35)23(32)17-30(4,5)12-9-3/h15-16,22-23,27H,7-14,17-20H2,1-6H3,(H,34,35)/t22-,23+,27-/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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. 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.

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.

Products are for research use only. Not for human use.