Granzyme B Inhibitor Z-AAD-CH2Cl

Z-AAD-CH2Cl (Z-AAD-CMK) is a cell-permeable and irreversible inhibitor of granzyme B [1].

Granzyme B is an apoptosis-inducing factor that expressed in natural killer (NK) cells, the granules of cytotoxic lymphocytes (CTLs) and cytotoxic T cells, and plays an important role in inducing inflammation and extracellular matrix remodelling [1].

Z-AAD-CH2Cl (Z-AAD-CMK) is a cell-permeable and irreversible granzyme B inhibitor. In human C-28/12 chondrocytes expressed the surface antigens of NK cells, Z-AAD-CMK dose-dependently inhibited chondrocyte cytotoxicity against K562 cells that was dependent on granzyme B [1]. In the oral squamous cell carcinoma cell line OSC-3, Z-AAD-CMK reduced interleukin-2-activated lymphocytes (LAK cell)-enhanced caspase-3 activity to approximately 70% and inhibited DNA fragmentation by approximately 20% of the control. Z-AAD-CMK also inhibited the increase of reactive oxygen intermediates (ROI) induced by LAK cells to approximately half of the control [2]. In Tc1 cells, Z-AAD-CMK inhibited apoptosis [3].

References:
[1].  Saito S, Murakoshi K, Kotake S, et al. Granzyme B induces apoptosis of chondrocytes with natural killer cell-like cytotoxicity in rheumatoid arthritis. J Rheumatol, 2008, 35(10): 1932-1943.
[2].  Yamamoto T, Yoneda K, Ueta E, et al. Enhanced apoptosis of squamous cell carcinoma cells by interleukin-2-activated cytotoxic lymphocytes combined with radiation and anticancer drugs. Eur J Cancer, 2000, 36(15): 2007-2017.
[3].  Gorak-Stolinska P, Truman JP, Kemeny DM, et al. Activation-induced cell death of human T-cell subsets is mediated by Fas and granzyme B but is independent of TNF-alpha. J Leukoc Biol, 2001, 70(5): 756-766.