CLIK-148 

CLIK-148 is a highly selective, irreversible and orally active cysteine protease inhibitor, primarily targeting Cathepsin L. CLIK-148 effectively inhibits the Cathepsin L-dependent degradation of HMG-CoA reductase in the endoplasmic reticulum (ER) membrane. CLIK-148 inhibits the processing of proCCK by Cathepsin L, thereby reducing the production of CCK8 (HY-P0093). CLIK-148 inhibits the degradation of type I collagen by osteoclasts' secreted Cathepsin L, reducing tumor-induced bone metastasis and malignant hypercalcemia. CLIK-148 can be used for the studies of bone metabolism disorders and regulation of neuropeptide processing^[1][2][3][4].

CLIK-148 (100 nM-10 μM) at a concentration of 100 nM in rat liver, potently and specifically inhibits Cathepsin L activity, while exhibits almost no inhibition against Cathepsin B and C at 1 μM, and demonstrates only weak inhibition towards Cathepsin S and K at a concentration of 10 μM^[1].
CLIK-148 (50 μM, 24 h) inhibits the activity of Cathepsin L, thereby blocking the generation of CCK9 from proCCK and ultimately reducing the production of CCK8 in pituitary AtT-20 cells^[2].
CLIK-148 (1-10 nM, 72 h) effectively inhibit the degradation of bone collagen mediated by human and mouse osteoclasts activated by TNF-α^[3].
CLIK-148 (100 μM) effectively protects HMG-CoA reductase from pathological degradation in the context of C100 cell necrotic injury^[4].

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

CLIK-148 (1-10 mg/kg, i.p., single dose) significantly inhibits Cathepsin L in the liver of mice, while having no effect on the activity of Cathepsin B at all^[1].
CLIK-148 (50 mg/kg, p.o., once daily for 7 days) effectively prevents and treats malignant hypercalcemia caused by tumors in mice^[3].
CLIK-148 (32-128 mg/kg, p.o. or i.v., once daily for 7 days) effectively inhibit the direct bone metastasis and local bone destruction of colon cancer cells^[3].
CLIK-148 (100-200 mg/kg, p.o., once daily for 14 days) specifically inhibits the process by which cancer cells metastasize through the bloodstream to the bones in mice^[3].

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

410.47

C₂₂H₂₆N₄O₄

215098-90-1

CN(C)C([C@H](CC1=CC=CC=C1)NC([C@@H]2[C@H](O2)C(NCCC3=CC=CC=N3)=O)=O)=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Katunuma N, et al. Structure based development of novel specific inhibitors for cathepsin L and cathepsin S in vitro and in vivo. FEBS Lett. 1999 Sep 10;458(1):6-10.  [Content Brief]

  [2]. Beinfeld MC, et al. Cathepsin L plays a major role in cholecystokinin production in mouse brain cortex and in pituitary AtT-20 cells: protease gene knockout and inhibitor studies. Peptides. 2009 Oct;30(10):1882-91.  [Content Brief]

  [3]. Katunuma N, et al. Structure-based design of specific cathepsin inhibitors and their application to protection of bone metastases of cancer cells. Arch Biochem Biophys. 2002 Jan 15;397(2):305-11.  [Content Brief]

  [4]. Moriyama T, et al. 3-hydroxy-3-methylglutaryl coenzyme A reductase is sterol-dependently cleaved by cathepsin L-type cysteine protease in the isolated endoplasmic reticulum. Arch Biochem Biophys. 2001 Feb 15;386(2):205-12.  [Content Brief]