Inavolisib

Inavolisib Report

Name: Inavolisib Name (English): Inavolisib DrugBank ID: DB15275 Type: Small Molecule CAS Number: 2060571-02-8

Mechanism of Action: Inavolisib is a selective inhibitor of the Class I PI3Kα isoform (p110α). It binds to the ATP-binding site of PI3Kα, inhibiting the phosphorylation of phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-trisphosphate (PIP3). This reduces downstream activation of AKT and ribosomal protein S6, leading to decreased cell proliferation, metabolism, and angiogenesis. Inavolisib also specifically triggers the degradation of the mutant p110α protein.

Indication: Inavolisib is indicated in combination with palbociclib and fulvestrant for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy.

Contraindications: There are no specific contraindications listed beyond potential hypersensitivity to the drug or any of its components. Caution should be exercised in patients with a history of diabetes or kidney disease.

Pharmacokinetics:

• Absorption: The absolute oral bioavailability of inavolisib is 76%. Steady-state is reached by approximately day 5, with a Tmax of 3 hours. Food does not significantly affect pharmacokinetics.
• Distribution: Not specified in detail but it crosses cell membranes.
• Metabolism: Inavolisib appears metabolically stable in hepatocytes.
• Elimination: The total clearance of inavolisib is 8.8 L/h. It is a substrate of P-gp and BCRP/ABCG2 transporters.

Side Effects: Common side effects include:

• Neutropenia
• Thrombocytopenia
• Anemia
• Hyperglycemia
• Stomatitis
• Diarrhea
• Nausea
• Rash
• Decreased appetite
• Fatigue
• Headache
• COVID-19 infection