Undisclosed KAT6A/B inhibitor / Bayer - LARVOL DELTA

Development of a new class of KAT6A/B inhibitors with in vivo efficacy (AACR 2026) - "These inhibitors were first identified via high-throughput screening and subsequently refined through computational modelling and co-crystallization studies. The lead compound from this series, BAY-184, demonstrated efficacy in an in vivo proof-of-concept experiment, confirming its potential as a tool for targeting KAT6A/B activity."

Preclinical • Breast Cancer • Oncology • Solid Tumor • KAT6A • KAT6B

Identification of novel KAT6A/B inhibitors with enhanced antitumor activity and reduced hematologic toxicity (AACR 2025) - "Additionally, the inhibition of H3K23 acetylation in ZR-75-1 cells was analyzed by Western blotting. HLX97-069/053 emerged as the top two candidates, exhibiting superior enzymatic inhibition and enhanced selectivity against KAT5/7/8, along with more potent cytotoxic effects in ZR-75-1 cells, in head-to-head comparisons with PF-07248144. In summary, these preclinical data provide compelling evidence that we have identified novel KAT6A/B inhibitors with best-in-class potential. Confirmation of the final candidate will depend on the outcomes of the forthcoming pilot toxicity studies, with an IND application anticipated by the end of 2025."

Breast Cancer • Oncology • Solid Tumor • KAT6A

Novel combination therapy with a KAT6A/B inhibitor together with retinoids induces irreversible differentiation of neuroblastoma cells (AACR 2024) - "In this screen, we found that an inhibitor of the histone H3K23 acetyltransferases KAT6A/B, PF-9363, synergistically inhibits neuroblastoma cell growth in combination with retinoic acid. Importantly, this combination treatment renders the differentiated cell state irreversible, such that it is maintained after retinoic acid is withdrawn, with continued suppression of the adrenergic CRC and MYCN expression. In conclusion, the retino-sympathetic differentiated cell state induced by retinoic acid in neuroblastoma becomes irreversible when the cells are also treated with an inhibitor of the KAT6A/B histone H3K23 acetyltransferases, implicating the essential role of these enzymes in restoring the proliferative immature progenitor phenotype in adrenergic neuroblastoma cells."

Combination therapy • Neuroblastoma • Oncology • Solid Tumor • KAT6A • MYCN

Discovery and proteomic characterization of a novel KAT6A/B inhibitor (AACR 2025) - "Proteomic analysis of KAT6i sensitive and resistant cell lines highlighted several candidates for KAT6 predictive biomarker and shed light on the proteome-wide effects of KAT6 inhibition. In summary, these results support KAT6i drug development both within and outside ER+ breast cancer, as well as optimization of more selective KAT6 inhibitors to improve tolerability and therapeutic window."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • KAT6A

QLS1304, a highly potent and selective KAT6A/B inhibitor treating ER+HER2- breast cancer (AACR 2025) - "Collectively, QLS1304 appears to be a promising candidate for the treatment of ER+HER2- breast cancer given its efficacy in both SoC-sensitive and SoC-resistant models. Moving it forward into clinical trials is warranted both as single agent and combining with other therapies."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • KAT6A • KAT6B • KAT8