RP-182 acetate

RP-182 acetate is a synthetic immunomodulatory peptide that exerts anti-tumor effects by targeting the mannose receptor CD206 ( K d = 8 μM) on the surface of tumor-associated macrophages (TAMs). RP-182 acetate induces a conformational switch of the CD206 receptor, which activates NF-κB signaling and phagocytosis in CD206 high TAMs. RP-182 acetate has dual function: activation of canonical NF-κB signaling, triggering TNFα secretion and autocrine activation of the TNF receptor 1 ( TNFR1 ), leading to activation of caspase 8, apoptosis, and cell death. RP-182 acetate is used in pancreatic cancer and melanoma research ^{[1] [2]}.

In Vivo, RP-182 acetate (20 mg/kg, i.p., every other day for 2 weeks) significantly inhibits tumor growth B16 melanoma and KP16 pancreatic model and improves mice immunogenicity^[1][2]. RP-182 acetate (20 mg/kg, i.p., once daily for 18 days) significantly alleviates pulmonary fibrosis in mice^[2].

In Vitro, RP-182 acetate (1 nM-1 mM, 48 h) increases cell killing of CD206high M2-like macrophages with an IC₅₀ of 17.6 μM through the MyD88/NF-κB pathway^[1][2]. RP-182 acetate (0.1 μM, 2-24 h) internalizes CD206, activated NF-κB, and increased IRF7 phosphorylation in IL-4-polarized M2 bone marrow-derived macrophages^[1][2]. RP-182 acetate (3-30 μM, 24 h) increases levels of inflammatory factors secreted by macrophages, indicating immune reprogramming^[1][2].

References:
[1]. Singh SS, et al. Fatty Acid Derivatization and Cyclization of the Immunomodulatory Peptide RP-182 Targeting CD206high Macrophages Improve Antitumor Activity. Mol Cancer Ther. 2024 Dec 3;23(12):1827-1841.
[2]. Jaynes JM, et al. Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and innate antitumor immune responses. Sci Transl Med. 2020 Feb 12;12(530):eaax6337.