181
Views
0
CrossRef citations to date
0
Altmetric
Research Articles

Pharmacological inhibition of cathepsin C (CatC) as a potential approach for cancer therapeutics

, , &
Pages 8682-8689 | Received 26 Jul 2022, Accepted 08 Oct 2022, Published online: 20 Oct 2022
 

Abstract

Studies have established that proteolytic enzyme inhibition holds significant promise in cancer prevention and treatment. Cathepsin C (CatC) is conserved lysosomal cysteine dipeptidyl aminopeptidase, which is the key for pro-inflammatory neutrophil serine protease activation and biological functioning. This makes CatC as a promising therapeutic drug target for the management of different cancer types. Considering this, using a wide range of computer aided drug-designing applications, several inhibitors are shortlisted against CatC active pocket, which interact with the enzyme with high affinity and form strong intermolecular interaction network. Compared to control, three molecules ASN_06916232, ASN_06917112 and ASN_06916892 are filtered as best binders of the CatC active pocket with binding energy value of −10.9 kcal/mol, −10.9 kcal/mol and −10.7 kcal/mol, respectively. These compounds interact with several important active side residues of CatC such as Ser233, Cys234, Gly277, Asn380 and His38. Furthermore, the complexes of these compounds with CatC reveal very stable dynamics with average RMSD value less than 3 Å. The binding energy analysis further indicates the compounds to have very stable van der Waals and electrostatic energies. In conclusion, these molecules are promising and require experimental validation to prove them as anti-CatC molecules.

Communicated by Ramaswamy H. Sarma

Disclosure statement

No conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.