Inavolisib’s mechanism of action and target analysis

Inavolisib is a selective inhibitor of the α subunit of phosphatidylinositol 3-kinase (PI3K) with strong targeting and therapeutic potential. The PI3K pathway plays an important role in the occurrence and development of various cancers, especially in malignant tumors such as breast cancer. The activation of PI3K is often the driving force for cell proliferation and survival. Specifically, PI3Kα is a catalytic subunit in the PI3K family. It phosphorylates phosphatidylinositol (PIP2) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3), thereby activating downstream signaling pathways, including AKT, mTOR, etc. These signaling pathways directly regulate cell proliferation, survival and metabolism.

The mechanism of action of inaliset is mainly reflected in its inhibition ofPI3Kα subunit, reducing the synthesis of PIP3, thereby inhibiting the phosphorylation of downstream molecules such as AKT, thereby inhibiting the proliferation of tumor cells and inducing apoptosis. Especially in breast cancer cells with PIK3CA gene mutations, PIK3CA mutations usually lead to continued activation of the PI3K pathway, allowing tumor cells to escape the normal apoptosis process and show drug resistance. Inaliset can specifically degrade the mutated PI3K catalytic subunit p110α (encoded by the PIK3CA gene), thereby effectively inhibiting the proliferation of cancer cells.

In in vitro studies, inaliset has a significant inhibitory effect on breast cancer cell lines, especially in breast cancer cell lines with PIK3CA mutations, inaliset can effectively reduce the proliferation rate of tumor cells and reduce tumor burden by inducing apoptosis. Compared with single treatment or other drug combinations, the combined use of inaliset with palbociclib (CDK4/6 inhibitor) and fulvestrant (estrogen receptor antagonist) can significantly enhance the inhibitory effect of tumor growth, showing its potential in the treatment of various tumors such as breast cancer.

Inaliset also showed good anti-tumor effects in an in vivo xenograft mouse model. For PIK3CA-mutated, estrogen receptor-positive breast cancer xenograft models, inaliside can significantly slow down tumor growth, further verifying its effectiveness as a targeted therapy.

Reference materials:https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5de59f5b-e5db-410f-b692-658686ef4107