TPCK

TPCK (L-1-Tosylamido-2-phenylethyl chloromethyl ketone; L-TPCK) is an effective serine protease inhibitor and also a blocker of the PDK1/Akt pathway. TPCK can modify the E7 protein in actively keratinocyte cells. TPCK can induce cellular apoptosis, suppress tumor growth, reduce hypoxic-ischemic brain injury in rat pups, and affect vascular permeability in inflamed rats^{[1][2][3][4][5]}. In Vitro:TPCK shows slight toxicity to mammalian cells (CC₅₀ = 138.8 µM), but it significantly inhibits the pre-flagellate morphology of L. amazonensis PH8 and Josefa strains (IC₅₀ values of 14.6 µM and 31.7 µM, respectively), with an IC₅₀ value of 11.3 µM for the pre-flagellate morphology of L. infantum. Additionally, TPCK is also effective against the intracellular amastigote form, showing IC₅₀ values of 14.2 µM and 16.6 µM for L. amazonensis PH8 and Josefa strains, and 21.7 µM for the amastigote form of L. infantum^[2].
TPCK (40 μM, 1 h) enhances wortmannin-dependent caspase activity in LNCaP cells but inhibits TRAIL-dependent caspase activity^[3].
TPCK (40 μM, 1 h) inhibits the formation of TRAIL-DISC in PC3 cells but does not inhibit the formation of Fas-DISC and reduces caspase2 levels^[3].
TPCK (0-40 μM, 24 h) kills PC3 cells in a dose-dependent manner, inducing apoptosis^[3].
TPCK (40 μM, 3 h) reduces the level of BAD-ser136 in LNCaP cells and eliminates AR in the cytoplasm and granules^[3]. In Vivo:TPCK (15-60 mg/kg, intraperitoneal injection, three times a week for ten doses) reduces the activity of anti-Leishmania parasites in mice^[2].
TPCK (5-100 mg/kg, intraperitoneal injection, single dose) diminishes DNA fragmentation, nitric oxide production, and brain damage in a neonatal mouse model of hypoxic-ischemic brain injury^[4].
TPCK (0.5-20 mg/kg, injected into the air sac, single dose) increases vascular permeability in inflamed rats, which then decline^[5].