SF1126

PI3K Inhibitor Conjugate (peptide Drug Conjugate)Rx: InvestigationalCompound: Investigational

Also known as: LY294002-RGDS conjugate, SF 1126

Educational Only — Not medical advice. Consult a qualified clinician before using any peptide.

Summary

SF1126 is an integrin-targeted prodrug of the pan-PI3K inhibitor LY294002. The RGDS peptide moiety directs the compound to integrin-expressing tumor vasculature and cancer cells, improving tumor delivery relative to LY294002 alone. It has been evaluated in Phase I/II clinical trials for advanced solid tumors and hematologic malignancies, including B-cell malignancies, demonstrating manageable tolerability and preliminary antitumor activity.

Mechanism of Action

SF1126 is a prodrug consisting of LY294002 (a pan-PI3K inhibitor) covalently conjugated to an RGDS tetrapeptide targeting integrin receptors on tumor vasculature. Upon binding integrins (αvβ3, αvβ5, α5β1) expressed on tumor endothelium and cancer cells, the conjugate is internalized and LY294002 is released, inhibiting PI3K (class I, II, III) and mTOR/DNA-PK, thereby blocking the PI3K/Akt/mTOR signaling pathway to suppress tumor cell proliferation, survival, and angiogenesis.

Routes of Administration

Intravenous

Goals & Uses

  • Treatment of B-cell malignancies (CLL, B-cell NHL)Oncology / HematologyLow
  • Treatment of advanced solid tumorsOncologyLow
  • PI3K/Akt/mTOR pathway blockadeSignal Transduction InhibitionModerate
  • Tumor angiogenesis inhibitionOncology / AntiangiogenicModerate

Contraindications

  • Severe hepatic impairmentOrganModerateLiver function concerns
  • Known hypersensitivity to LY294002 or RGDS componentsAllergyHigh
  • Active uncontrolled infectionInfectious DiseaseModerate

Adverse Effects

  • HyperglycemiaMetabolicCommonAbnormally high blood glucose
  • Nausea/vomitingGastrointestinalCommon
  • FatigueGeneralCommonLow energy or tiredness
  • Elevated liver enzymes (transaminases)HepaticUncommon
  • Infusion-related reactionsHypersensitivityUncommon
  • DiarrheaGastrointestinalUncommonLoose or frequent stools

Drug Interactions

  • Antidiabetic agents (insulin, metformin)Moderate
  • Anticoagulants (warfarin, heparin)Moderate
  • CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin)Moderate

Population Constraints

  • PregnancyReproductive SafetyAbsolute
  • Pediatric patientsAgeRelative
  • Patients with diabetes mellitusMetabolicRelative

Regulatory Status

  • European UnionUnknownNo EMA approval or formal clinical trial authorization publicly documented as of knowledge cutoff.
  • United StatesInvestigationalIND filed; Phase I/II clinical trials conducted under FDA IND. Not approved for any indication.
  • United KingdomUnknownNo MHRA approval documented.

Investigational agent; has entered Phase I/II clinical trials (e.g., NCT00907205). Not approved by FDA, EMA, or other regulatory authorities for any indication.

Evidence & Sources

No sources recorded yet.

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