Overview
TY-0540 is an innovative small-molecule kinase inhibitor independently developed by TYK Medicines, which displays high selectivity towards CDK2/4/6 and exhibits favorable oral bioavailability. It is intended for the treatment of HR+/HER- breast cancer and other solid tumors in patients who have received previous CDK4/6 treatment and become drug resistant. TY-0540 has demonstrated high efficacy and favorable safety in the early research and development stage. On June 17, 2023, TY-0540 obtained the SMP letter from the FDA, and on June 20, 2023, the CDE accepted the IND.
Mechanism of Action
Cyclin-dependent kinases (CDKs) are Serine/Threonine kinase proteins that play a critical role in regulating the cell cycle progression and cell division. The catalytic activity is modulated by cyclins and CDK inhibitors. CDKs regulate the cell cycle checkpoints and DNA transcriptions and are considered crucial regulators in the cell division process. Although CDK 4/6 inhibitors in combination with endocrine therapy are the first-line therapy for HR+/HER2- breast cancer, the treatment still faces challenges due to the intrinsic resistance and acquired resistance to CDK 4/6 inhibitors. Approximately 20% of patients who received CDK4/6 inhibitor treatment showed an ineffective response, referred to as intrinsic resistance. The activation of Cyclin E and subsequent upregulation of CDK2 in response to the suppression of CDK4/6 activity can result in Rb phosphorylation and tumor cell proliferation, which can contribute to acquired resistance. Therefore, simultaneously targeting the CDK2, CDK4, and CDK6 is a promising strategy to overcome acquired drug resistance.
