G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer.

ABSTRACT:

Purpose

The combination of targeting the CDK4/6 and estrogen receptor (ER) signaling pathways with palbociclib and fulvestrant is a proven therapeutic strategy for the treatment of ER-positive breast cancer. However, the poor physicochemical properties of fulvestrant require monthly intramuscular injections to patients, which limit the pharmacokinetic and pharmacodynamic activity of the compound. Therefore, an orally available compound that more rapidly reaches steady state may lead to a better clinical response in patients. Here, we report the identification of G1T48, a novel orally bioavailable, non-steroidal small molecule antagonist of ER.

Methods

The pharmacological effects and the antineoplastic mechanism of action of G1T48 on tumors was evaluated using human breast ca

SUBMITTER: Andreano KJ 

PROVIDER: S-EPMC7103015 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature