Gedatolisib (CAS 1197160-78-3) is a highly potent dual inhibitor of PI3K and mTOR developed by Pfizer, also known as PKI-587 and PF-05212384. The compound demonstrates sub-nanomolar activity against PI3Kα and mTOR, positioning it as a clinically relevant tool for oncology research. Enamine offers Gedatolisib as a high-purity screening sample for pharmacological and translational studies.
Gedatolisib molecular structure is based on a bis-morpholino triazine scaffold linked via a urea bridge to a piperidine-containing phenyl group, with molecular formula C₃₂H₄₁N₉O₄ and a molecular weight of 615.73 g/mol. The PF-05212384 chemical structure enables simultaneous engagement of the ATP-binding sites of PI3K isoforms and both mTOR complexes. Researchers examine the PF-05212384 structure to understand its selectivity profile and binding geometry within the PI3K/mTOR catalytic domains. The compound is registered under CAS 1197160-78-3 and is administered intravenously in clinical settings.
Application of PF-05212384
PF-05212384 is applied in oncology research targeting PI3K/mTOR pathway dysregulation across a broad range of solid tumors and hematological malignancies. Gedatolisib Pfizer development history includes Phase 1 and Phase 2 clinical studies in advanced solid tumors, AML, ovarian cancer, and breast cancer. The compound is used in combination studies with chemotherapy agents, CDK4/6 inhibitors, and EGFR inhibitors to investigate synergistic pathway suppression and resistance mechanisms.
Biochemical and Physiological Actions
The PF-05212384 mechanism of action involves simultaneous inhibition of all class I PI3K isoforms and mTOR, with IC₅₀ values of 0.4 nM for PI3Kα and 1.6 nM for mTOR in cell-free assays. By blocking both mTORC1 and mTORC2 complexes, Gedatolisib prevents the feedback reactivation of AKT commonly observed with selective mTORC1 inhibitors. This dual blockade suppresses downstream effectors including p-AKT, p-S6K, and p-4EBP1, leading to cell cycle arrest and apoptosis in PI3K/mTOR-dependent tumor cells. In clinical tumor biopsies, PF-05212384 demonstrably inhibited pathway effectors following intravenous dosing.
Features and Benefits of PF-05212384
Gedatolisib (PKI-587, CAS 1197160-78-3) offers a clinically validated activity profile with distinct advantages for translational research:
- sub-nanomolar potency against PI3Kα (IC₅₀ 0.4 nM) and mTOR (IC₅₀ 1.6 nM) with pan-class I isoform coverage;
- simultaneous mTORC1 and mTORC2 inhibition preventing AKT reactivation feedback;
- clinical Phase 1/2 data available across multiple tumor types, supporting translational relevance;
- well-characterized PF-05212384 structure enabling rational combination study design.
When sourced as EBC-221079, the compound is provided with analytical quality control data for consistent use in biochemical and cell-based assays.
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