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Ref Type Journal Article
PMID (19010932)
Authors Xue Q, Hopkins B, Perruzzi C, Udayakumar D, Sherris D, Benjamin LE
Title Palomid 529, a novel small-molecule drug, is a TORC1/TORC2 inhibitor that reduces tumor growth, tumor angiogenesis, and vascular permeability.
Journal Cancer research
Vol 68
Issue 22
Date 2008 Nov 15
Abstract Text It has become clear that the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is central for promoting both tumor and tumor stroma and is therefore a major target for anticancer drug development. First- and second-generation rapalogs (prototypical mTOR inhibitors) have shown promise but, due to the complex nature of mTOR signaling, can result in counterproductive feedback signaling to potentiate upstream Akt signaling. We present a novel PI3K/Akt/mTOR inhibitor, Palomid 529 (P529), which inhibits the TORC1 and TORC2 complexes and shows both inhibition of Akt signaling and mTOR signaling similarly in tumor and vasculature. We show that P529 inhibits tumor growth, angiogenesis, and vascular permeability. It retains the beneficial aspects of tumor vascular normalization that rapamycin boasts. However, P529 has the additional benefit of blocking pAktS473 signaling consistent with blocking TORC2 in all cells and thus bypassing feedback loops that lead to increased Akt signaling in some tumor cells.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
RES-529 RES-529 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
RES-529 Palomid 529|P529 mTOR Inhibitor 51 RES-529 (Palomid 529) inhibits mTOR signaling though mTORC1 and mTORC2, which prevents cell proliferation (PMID: 19010932).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown malignant glioma not applicable RES-529 Preclinical - Cell line xenograft Actionable In a preclinical study, RES-529 (Palomid 529) inhibited tumor growth and angiogenesis in glioma cell line xenograft models (PMID: 19010932). 19010932