Abstract
Psoriasis therapy remains an extremely relevant area of modern drug design, due to necessity of adverse reaction reduction, inherent for actual methods of therapy. It was established that two serine proteases—neutrophil elastase 1 (HNE1) and cathepsin G (CatG)—are the key agents in psoriasis development. The collected molecular data for the presented targets form the basis for the molecular modeling strategy for the search for and identification of new target-specific inhibitors. The result of this work is a group of high-priority small-molecule compounds with double-targeted affinity, which are able to suppress the pro-psoriatic processes induced by the considered serine proteases at the initial stage of the disease.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Gabay, C. and Towne, J.E., Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions, J. Leukocyte Biol., 2015, vol. 97, no. 4, pp. 645–652.
Sullivan, G.P., Davidovich, P.B., Sura-Trueba, S., Belotcerkovskaya, E., Henry, C.M., Clancy, D.M., Zinoveva, A., Mametnabiev, T., Garabadzhiu, A.V., and Martin, S.J., Identification of small-molecule elastase inhibitors as antagonists of IL-36 cytokine activation, FEBS Open Biol., 2018, vol. 8, no. 5, pp. 751–763.
Nero, T.L., Parker, M.W., and Morton, C.J., Protein structure and computational drug discovery, Biochem. Soc. Ttransact., 2018, vol. 46, no. 5, pp. 1367–1379.
Clancy, D.M., Sullivan, G.P., Moran, H.B.T., Henry, C.M., Reeves, E.P., McElvaney, N.G., Lavelle, E.C., and Martin, S.J., Extracellular neutrophil proteases are efficient regulators of IL-1, IL-33, and IL-36 cytokine activity but poor effectors of microbial killing, Cell Rep., 2018, vol. 22, no. 11, pp. 2937–2950.
Henry, C.M., Sullivan, G.P., Clancy, D.M., Afonina, I.S., Kulms, D., and Martin, S.J., Neutrophil-derived proteases escalate inflammation through activation of IL-36 family cytokines, Cell Rep., 2016, vol. 14, no. 4, pp. 708–722.
Dietrich, D. and Gabay, C., Inflammation: IL-36 has proinflammatory effects in skin but not in joints, Nat. Rev. Rheumatol., 2014, vol. 10, no. 11, pp. 639–640.
D'Erme, A.M., Wilsmann-Theis, D., Wagenpfeil, J., Holzel, M., Ferring-Schmitt, S., Sternberg, S., Wittmann, M., Peters, B., Bosio, A., Bieber, T., and Wenzel, J., IL-36gamma (IL-1F9) is a biomarker for psoriasis skin lesions, J. Invest. Dermatol., 2015, vol. 135, no. 4, pp. 1025–1032.
Tabeshpour, J., Sahebkar, A., Zirak, M.R., Zeinali, M., Hashemzaei, M., Rakhshani, S., and Rakhshani, S., Computer-aided drug design and drug pharmacokinetic prediction: A mini-review, Curr. Pharm. Design, 2018, vol. 24, no. 26, pp. 3014–3019.
Hooshdaran, B., Kolpakov, M.A., Guo, X., Mil-ler, S.A., Wang, T., Tilley, D.G., Rafiq, K., and Sabri, A., Dual inhibition of cathepsin G and chymase reduces myocyte death and improves cardiac remodeling after myocardial ischemia reperfusion injury, Basic Res. Cardiol., 2017, vol. 112, no. 6, p. 62.
McLoed, A.G., Sherrill, T.P., Cheng, D.S., Han, W., Saxon, J.A., Gleaves, L.A., Wu, P., Polosukhin, V.V., Karin, M., Yull, F.E., Stathopoulos, G.T., Georgoulias, V., Zaynagetdinov, R., and Blackwell, T.S., Neutrophil-derived IL-1beta impairs the efficacy of NF-kappaB inhibitors against lung cancer, Cell Rep., 2016, vol. 16, no. 1, pp. 120–132.
Repasky, M.P., Shelley, M., and Friesner, R.A., Flexible ligand docking with Glide, Curr. Protoc. Bioinform., 2007, chapter 8, pp. 8–12.
Nussbaum, F., Karthaus, D., Anlauf, S., Klein, M., Li, V.M.-J., Meibom, D., Lustig, K., and Schamberger, J., PCT Int. Appl. no. WO2009080199, Chem. Abstr., 2009, vol. 151, pp. 101–192.
Ilyin, A., Kysil, V., Krasavin, M., Kurashvili, I., and Ivachtchenko, A.V., Complexity-enhancing acid-promoted rearrangement of tricyclic products of tandem Ugi 4CC/intramolecular Diels–Alder reaction, J. Org. Chem., 2006, vol. 71, no. 25, pp. 9544–9547.
Baell, J.B. and Holloway, G.A., New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays, J. Med. Chem., 2010, vol. 53, no. 7, pp. 2719–2740.
Verdonk, M.L., Berdini, V., Hartshorn, M.J., Mooij, W.T., Murray, C.W., Taylor, R.D., and Watson, P., Virtual screening using protein-ligand docking: avoiding artificial enrichment, J. Chem. Inform. Comp. Sci., 2004, vol. 44, no. 3, pp. 793–806.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.
Additional information
Translated by M. Batrukova
Rights and permissions
About this article
Cite this article
Krasavin, M.Y., Gureev, M.A., Garabadzhiu, A.V. et al. Inhibition of Neutrophil Elastase and Cathepsin G As a New Approach to the Treatment of Psoriasis: From Fundamental Biology to Development of New Target-Specific Drugs. Dokl Biochem Biophys 487, 272–276 (2019). https://doi.org/10.1134/S1607672919040082
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1607672919040082