IMPACT THERAP-B (07630) has nominated IMP2794 as a preclinical candidate compound (PCC), a highly specific PROTAC targeting KAT6A derived from the company's proprietary targeted protein degradation platform.

IMPACT THERAP-B (07630) announced that InnoCare Pharma has nominated IMP2794 as a preclinical candidate compound (PCC), which is a KAT6A-specific degrading PROTAC. IMP2794 is the first PCC discovered by InnoCare Pharma based on its proprietary targeted protein degradation platform. IMP2794 is a highly efficient and selective degrader of KAT6A, with over 1000-fold selectivity against KAT6B. This compound demonstrates significant cytotoxic activity against tumor cells in vitro and exhibits very low hematotoxicity. IMP2794 shows excellent in vivo antitumor effects in both sensitive and resistant breast cancer CDX models. Notably, IMP2794 exhibits extremely high oral bioavailability in various rodent and non-rodent animal models, suggesting that it may achieve ideal drug exposure in humans. KAT6A is a member of the histone acetyltransferase (HAT) MYST family, which catalyzes histone acetylation to promote chromatin opening and activate gene transcription. This protein is highly expressed in various cancers, particularly in estrogen receptor-positive (ER+) breast cancer. However, KAT6A's homolog KAT6B shares structural and sequence homology with KAT6A, making it challenging to achieve selective inhibition of KAT6A through traditional small molecule inhibitors. Additionally, the inhibition of KAT6B is associated with potential hematotoxicity. This nomination marks InnoCare Pharma's first preclinical candidate compound (PCC) derived from its proprietary targeted protein degradation platform (which encompasses protein degradation-targeted chimeras (PROTAC)), validating the technological maturity and output capability of the platform. The company has established a degradation platform supported by an E3 ligand library and linker library, allowing for the rapid assembly of PROTAC molecules with excellent oral bioavailability. These tools enable selective and tunable degradation of previously "undruggable" targets, widening the therapeutic window and reducing toxicity. This mechanism complements the company's ADC platform, supporting multidimensional exploration of cancer targets.