hsclpp

ZK53 is a selective and potent activator of mitochondrial casein hydrolase protease P (HsClpP).ZK53 induces apoptosis and inhibits the hydrolysis of alpha-casein by HsClpP.ZK53 inhibits tumour growth in xenografts and native mouse models.

HsClpP activator-1 (compound 24) is a potent activator of HsClpP, with an EC50 of 0.22 μM. It effectively inhibits cancer cell growth, exhibiting IC50 values ranging from 0.1 to 1 μM.

CLPP-2068 has oral activity and is an activator of human casein hydrolase P (HsClpP) (EC50=50.4 nM). CLPP-2068 exhibits anti proliferative effects (IC50=5.2 nM) in OCI-LY10 cells, and can also reduce mitochondrial membrane potential, increase mitochondrial ROS levels, and induce mitochondrial dysfunction. CLPP-2068 blocks the cell cycle in G1 phase and induces apoptosis in OCI-LY10 cells. CLPP-2068 exhibits anti-tumor activity in a mouse xenograft model.

NCA029 is a potent activator of human caseinolytic protease P (HsClpP) with an EC50 of 0.15 μM. It targets HsClpPP and triggers an ATF3-dependent integrated stress response, resulting in the death of colon cancer cells.

Antitumor agent-151 (7k) is a notable HsClpP agonist and a potential candidate for leukemia treatment. This compound significantly boosts the proteolytic activity of HsClpP (EC50= 0.79 μM) and exhibits remarkable in vitro antitumor activity (IC50= 0.038 μM). Additionally, Antitumor agent-151 (7k) induces apoptosis.

SL44 is an agonist of human caseinolytic protease P (HsClpP) with an EC50 of 1.30 μM. It inhibits LM3 proliferation with an IC50 of 3.1 μM and induces apoptosis in liver cancer cells by degrading respiratory chain complex subunits. In mouse models, SL44 demonstrates antitumor activity without significant toxicity (LD50=400 mg/kg) and exhibits favorable pharmacokinetic properties in rat models.

(R)-ZG197 is a compound that acts as a highly selective activator for Staphylococcus aureus Caseinolytic protease P (Sa ClpP), exhibiting an effective concentration (EC50) of 1.5 μM. It also activates Homo sapiens ClpP (Hs ClpP) with an EC50 of 31.4 μM.