GS-563117

GS-563117 is the **major circulating metabolite** of the drug idelalisib, which is a selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor used in the treatment of hematological malignancies. GS-563117 is formed in vivo from idelalisib mainly via metabolism by aldehyde oxidase and, to a lesser extent, by CYP3A enzymes. Importantly, while GS-563117 is **inactive against PI3Kδ and other PI3K isoforms**, its pharmacological relevance arises from its potent and **irreversible inhibition of cytochrome P450 3A (CYP3A)**, especially CYP3A4. This inhibition can lead to significant drug-drug interactions by elevating plasma levels of drugs that are CYP3A substrates, which may increase their therapeutic effects and risks of adverse reactions. GS-563117 is highly protein bound (about 99%), not pharmacologically active against malignant cells, and is not a substrate of major hepatic uptake transporters OATP1B1 or OATP1B3. It is excreted primarily via the hepatobiliary route, with the majority in feces and a minor fraction in urine[3][4][5][6].