| Structural highlights
Disease
MASP2_HUMAN Defects in MASP2 are the cause of MASP2 deficiency (MASPD) [MIM:613791. MASPD is a disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease.[1] [2]
Function
MASP2_HUMAN Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their activation and to the formation of C3 convertase.[3]
Publication Abstract from PubMed
The complement system of innate immunity recognizes, opsonizes, and kills invading pathogens and damaged cells, and stimulates an inflammatory response. Inappropriate or excessive complement activity is associated with a wide variety of pathological conditions, and several drugs targeting complement components have been approved. Here we describe the discovery and structure-activity relationships of a novel class of 2-aminoimidazole-containing inhibitors of mannan-binding lectin-associated serine proteases -2 and -3 (MASP-2 and MASP-3), essential enzymes for activation of the lectin and alternative pathways of complement, respectively. With a high degree of target selectivity and favorable in vitro pharmacological properties, this inhibitor series has the potential to be developed as treatments for numerous diseases and pathological conditions.
Small molecule inhibitors of mannan-binding lectin-associated serine Proteases-2 and-3.,Nakhla MC, Comita J, Shapiro AB, Moussa SH, Chen A, Eyermann CJ, O'Donnell JP, Miller AA, Granger BA Eur J Med Chem. 2025 May 5;289:117238. doi: 10.1016/j.ejmech.2025.117238. Epub , 2025 Jan 9. PMID:40010268[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Stengaard-Pedersen K, Thiel S, Gadjeva M, Moller-Kristensen M, Sorensen R, Jensen LT, Sjoholm AG, Fugger L, Jensenius JC. Inherited deficiency of mannan-binding lectin-associated serine protease 2. N Engl J Med. 2003 Aug 7;349(6):554-60. PMID:12904520 doi:http://dx.doi.org/10.1056/NEJMoa022836
- ↑ Thiel S, Steffensen R, Christensen IJ, Ip WK, Lau YL, Reason IJ, Eiberg H, Gadjeva M, Ruseva M, Jensenius JC. Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms. Genes Immun. 2007 Mar;8(2):154-63. Epub 2007 Jan 25. PMID:17252003 doi:10.1038/sj.gene.6364373
- ↑ Matsushita M, Thiel S, Jensenius JC, Terai I, Fujita T. Proteolytic activities of two types of mannose-binding lectin-associated serine protease. J Immunol. 2000 Sep 1;165(5):2637-42. PMID:10946292
- ↑ Nakhla MC, Comita J, Shapiro AB, Moussa SH, Chen A, Eyermann CJ, O'Donnell JP, Miller AA, Granger BA. Small molecule inhibitors of mannan-binding lectin-associated serine Proteases-2 and-3. Eur J Med Chem. 2025 May 5;289:117238. PMID:40010268 doi:10.1016/j.ejmech.2025.117238
|
