Arvenin I

Arvenin I is a natural cucurbitacin glucoside that activates T cells within the cancer-competitive environment. Arvenin I covalently reacts with and hyperactivates MKK3, thereby reviving the mitochondrial fitness of exhausted T cells through the activation of the p38MAPK pathway^[1]. Arvenin I exhibits broad-spectrum antiproliferative against cancer cells^[2]. Arvenin I enhances antitumor effects both as a monotherapy and in combination with immune checkpoint inhibitors in mice^[1]. Arvenin I can be used for cancer research, such as colon cancer, breast cancer, lung cancer, and ovarian cancer^[1][2]. In Vitro:Arvenin I (0.5-4 μM, 48 h) displays no detectable induction of IL-2 in Jurkat PD-1 cells in the absence of PHA and PMA (HY-18739) and exhibits no significant cytotoxicity in Jurkat PD-1 cells at 4 μM, suggesting that it does not independently activate T cells but rather augments the PHA/PMA-induced activation of T cells^[1].
Arvenin I (0-30 μM, 24-48 h) forms a covalent bond with specific cysteine residues in AKT (Cys310) and MKK3 (Cys227) through its Michael acceptor moiety to activate the MKK3-p38MAPK signaling pathway, leading to increased IL-2 production^[1].
Arvenin I (250 nM, 2 h) enhances the mitochondrial bioenergetics in primary CD8⁺ T cells by increasing basal and maximal respiration as well as spare respiratory capacity through the p38MAPK pathway^[1].
Arvenin I (1-100 μM, 3 days) exhibits broad-spectrum antiproliferative activity against a panel of human cancer cell lines, with IC₅₀ values of 17.0, 49.4, 14.7 and 42.8 μM in A-549, HT-29, OVCAR, and MCF-7 cells, respectively^[2]. In Vivo:Arvenin I (6 mg/kg, i.p., every 3 days from day 10 to day 22) suppresses tumor growth in immunocompetent but not Rag2KO MC38 tumor-bearing mice, demonstrating adaptive immune-dependent efficacy^[1]