Undisclosed CDK4 inhibitor / TYK Medicines - LARVOL DELTA

Development of a novel selective CDK4 inhibitor for HR+/HER2- breast cancer (AACR 2026) - "It also exhibited synergistic antitumor effects when combined with fulvestrant, with good tolerability evidenced by stable animal body weight throughout the study. Preliminary in vitro combination studies revealed that pairing the selective CDK4 inhibitor with a CDK2 inhibitor or a PI3K inhibitor produced significant synergistic inhibitory effects on MCF7 and palbociclib-resistant MCF7 cells. Optimization of the lead compound is ongoing with the goal of identifying a preclinical candidate (PCC) for IND-enabling studies.# Apeng Liang and Meihua Li contributed equally to this work.* Correspondence authors."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Development of a novel selective CDK4 inhibitor for HR+/HER2- breast cancer (AACR 2025) - "In MCF7-xenograft mouse model, TY-2072 showed significant suppression of tumor growth in a dose-dependent manner at 20 and 40 mg/kg BID, TY-2072 exhibited synergetic effects with Fulvestrant on anti-tumor growth inhibition with good tolerance, evidenced by the maintenance of body weight of the animals throughout the study. TY-2072 demonstrates high selectivity against CDK4, and more than 17-fold selectivity against CDK6 compared to palbociclib, proving that TY-2072 is a CDK4 inhibitor rather than a CDK4/6 dual inhibitor. Western blot assays showed a dose-dependent reduction in phosphorylated RB (Ser780) in breast cancer cell lines after 48 hours TY-2072 treatment. The anti-proliferation effects of CDK4 inhibitors were assessed with MCF7 (breast cancer, CDK4 sensitive), JEKO-1 (mantle cell lymphoma), and MOLM13 (acute myeloid leukemia, CDK6 sensitive) through a CTG cell viability assay after 5-day incubation."

Acute Myelogenous Leukemia • Breast Cancer • Hematological Malignancies • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Leukemia • Lung Cancer • Lymphoma • Mantle Cell Lymphoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • KRAS