TPCK  (Synonyms: L-1-Tosylamido-2-phenylethyl chloromethyl ketone; L-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]}.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

351.85

C₁₇H₁₈ClNO₃S

402-71-1

Solid

White to off-white

CC1=CC=C(C=C1)S(N[C@@H](CC2=CC=CC=C2)C(CCl)=O)(=O)=O

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. H Stöppler, et al. The serine protease inhibitors TLCK and TPCK react with the RB-binding core of HPV-18 E7 protein and abolish its RB-binding capability. Virology. 1996 Mar 15;217(2):542-53.  [Content Brief]

  [2]. Patrícia de A Machado, et al. Effects of a Serine Protease Inhibitor N- p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum. Pharmaceutics.2022 Jun 29;14(7):1373.  [Content Brief]

  [3]. M H LeBlanc, et al. N-tosyl-L-phenylalanyl-chloromethylketone reduces hypoxic-ischemic brain injury in rat pups. Eur J Pharmacol. 2000 Mar 3;390(3):249-56  [Content Brief]

  [4]. K Watanabe, et al. Vascular permeability changes by proteinase inhibitors in carrageenin-induced inflammation in rats. Agents Actions. 1986 Mar;17(5-6):472-7.  [Content Brief]