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.
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- CAS No.: 215098-90-1
- 화학식: C22H26N4O4
- 분자량:410.47
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocol
- 순도&문서
- References
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Help & FAQs
All Cathepsin Isoforms
More
Biological Activity
제품 설명
IC50 & Target
[1]|
cathepsin L |
In Vitro
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. Further protocols information, click here.
In Vivo
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.
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Animal Model:LJC-1 cells induced direct bone metastasis and local bone resorption model of cancer established in CDF1 mice[3]
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Dosage:5 mg/kg
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Administration:Oral administration (p.o.), once daily for 7 days
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Result:Significantly reduced the serum calcium level in mice.
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Animal Model:Colon tumor 26 PMF-15 cells induced hypercalcemia of malignancy model established in CDF1 mice[3]
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Dosage:32, 64 and 128 mg/kg
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Administration:Oral administration (p.o.) or intravenous injection (i.v.), once daily for 7 days
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Result:Significantly inhibited the decline of calcium content and protect the bones.
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Animal Model:Melanoma A375 cells induced distant bone metastasis model established in CDF1 mice[3]
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Dosage:100 and 200 mg/kg
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Administration:Oral administration (p.o.), once daily for 14 days
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Result:Reduced the area of the metastatic lesion significantly to 1.0 mm². Did not inhibit the metastasis of cancer cells to other organs such as the liver, muscles, and gums.
Chemical Information
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CAS No. 215098-90-1
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분자량 410.47
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화학식 C22H26N4O4
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SMILES
CN(C)C([C@H](CC1=CC=CC=C1)NC([C@@H]2[C@H](O2)C(NCCC3=CC=CC=N3)=O)=O)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocol
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Intracardiac/Intra-Arterial Metastasis Xenograft
Intracardiac xenograft metastasis models are based on the direct delivery of fluorescent or bioluminescent tumor cells into the left ventricle of immunocompromised mice, allowing systemic arterial dissemination that mimics hematogenous spread and enables colonization of distant organs such as bone, brain, and lung. Real-time bioluminescence imaging (BLI) is used to non-invasively track tumor cell seeding, survival, and metastatic outgrowth over time, reflecting early arrest in capillary beds followed by organ-specific colonization and proliferation.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
순도&문서
References
[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]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CLIK-148 Related Classifications
HY-164634 Related Classifications
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