Peptides›Immune›Tuftsin

Tuftsin

/ Endogenous tetrapeptide — produced by leukokininase cleavage of IgG Fc; synthesised commercially

TIER 3 · PreclinicalN = 0 · TESTING PENDINGMW 500.60 g·mol⁻¹

ALIAS · TKPR (Thr-Lys-Pro-Arg) · Phagocytosis-stimulating tetrapeptide · Leukokinin tetrapeptide

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequenceTKPR (Thr-Lys-Pro-Arg)

MW · 500.60CLASS · Endogenous tetrapeptide — produced by leukokininase cleavage of IgG Fc; synthesised commerciallyCATEGORY · Immune

Tier 3. Native physiological tetrapeptide cleaved from the Fc region of IgG by leukokininase; foundational immunology literature dating to 1972 (Najjar's discovery). Despite robust phagocytosis-stimulating activity in vitro and in rodent models, tuftsin and analogs have not translated into approved therapeutics in over 50 years.

§ B · Mechanism of action

Tuftsin binds to a tuftsin receptor on phagocytes (the molecular identity has been variously assigned; neuropilin-1 is a current candidate) and stimulates phagocytic activity, chemotaxis, and antigen processing. The endogenous tetrapeptide is thought to participate in the normal opsonisation-and-clearance cycle of antibody-coated targets.

§ C · Human clinical evidence

Tier 3. Foundational rodent and in-vitro evidence reviewed by Siemion (1999). Subsequent work has explored tuftsin-conjugated drug delivery (using the tetrapeptide as a phagocyte-targeting moiety) and macrophage polarisation in tumor immunology contexts; no direct human therapeutic approval.

§ D · Primary literature

PubMed4116440Najjar VA et al. — A new phagocytosis-stimulating tetrapeptide hormone, tuftsin, and its role in disease · Journal of the Reticuloendothelial Society · in-vitroOriginal characterisation of the leukokinin-derived TKPR tetrapeptide, demonstrating dose-dependent stimulation of phagocytosis by polymorphonuclear leukocytes.Limitations: Foundational discovery paper; no in-vivo therapeutic data.1972

PubMed10465518Siemion IZ et al. — Tuftsin: on the 30-year anniversary of Victor Najjar's discovery · Peptides · reviewComprehensive review of tuftsin pharmacology three decades after discovery: receptor pharmacology, structure-activity relationships, and the failure of tuftsin and analogs to translate into approved therapeutics despite robust in-vitro phagocytosis stimulation.Limitations: Narrative review; pre-dates more recent work on tuftsin-conjugated drug delivery and macrophage polarisation.1999

§ F · Safety signal

No formal Phase 1 human safety database. Endogenous tetrapeptide nature suggests low intrinsic toxicity but does not substitute for direct clinical safety data.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

The 50-year gap between robust preclinical pharmacology and zero approved therapeutic is itself a signal. Modern interest is largely in tuftsin as a delivery moiety rather than as a free-peptide therapy.