Proteases, also known as proteolytic enzymes, are enzymes that catalyze the breakdown of proteins by hydrolysis of peptide bonds. By cleaving proteins, proteases are involved in the control of a large number of key physiological processes such as cell-cycle progression, cell proliferation and cell death, DNA replication, tissue remodeling, haemostasis (coagulation), wound healing and the immune response. So far, inappropriate proteolysis has been found to have a major role in cancer as well as cardiovascular, inflammatory, neurodegenerative, bacterial, viral and parasitic diseases. Because excessive proteolysis can be prevented by blocking the appropriate proteases, this area is widely explored by pharmaceutical companies. Their mechanism of action classifies the large family of proteases as either serine, cysteine or threonine proteases (amino-terminal nucleophile hydrolases), or as aspartic, metallo and glutamic proteases (with glutamic proteases being the only subtype not found in mammals so far). Interestingly, the serine and cysteine proteases act directly as nucleophiles to attack the substrate (by generating covalent acyl enzyme intermediates). On the other hand, the aspartyl and zinc proteases activate water molecules as the direct attacking species on the peptide bond. Proteases of the different classes can be further grouped into families on the basis of amino acid sequence comparison, and families can be assembled into clans based on similarities in their three-dimensional structures.
Five subfamilies of aspartic proteases (EC 3.4.23.-) are classified, all sharing a highly conserved sequence of Asp-Thr-Gly. Compared to the three other types of proteases, serine, cysteine, and metalloproteases, aspartic proteases comprise a relatively small group. The aspartic proteases of many pathogens represent attractive targets for inhibitor design to control the progression of these diseases. The development of effective HIV protease inhibitor drugs for the treatment of HIV infection in AIDS illustrates the importance of this approach. Most of the aspartic proteases belong to a pepsin structural superfamily, having homologous primary and tertiary structures and nearly identical catalytic apparatus.
 Targeting proteases: successes, failures and future prospects. Boris Turk. Nature Reviews – Drug Discovery. Volume 5, 2006, 785-799.
 Proteases: Multifunctional Enzymes in Life and Disease. C. López-Otín, J.S. Bond. J. Biol. Chem. 2008, 283, 30433-30437.
 R. Mannhold, H. Kubinyi, G. Folkers (Editors). Aspartic Acid Proteases as Therapeutic Targets. Methods and Principles in Medicinal Chemistry.. 2010. Wiley-VCH Verlag GmbH & Co. KGaA. ISBN: 9783527318117.
|Axon ID||Name||Description||From price|
|1125||BACE-1 Inhibitor||BACE 1 inhibitor||€110.00|
|2117||Begacestat||Selective γ-secretase inhibitor (GSI)||€85.00|
|1441||BMS 232632||Protease inhibitor||€105.00|
|1487||BZ, γ-Secretase Inhibitor||γ-Secretase inhibitor (GSI)||€70.00|
|1753||Compound 120||Deuterated Protease inhibitor (see Axon 1441)||€115.00|
|1488||DBZ, γ-Secretase Inhibitor||γ-Secretase inhibitor (GSI)||€65.00|
|2225||LY 2811376||The first orally available non-peptidic BACE1 inhibitor||€125.00|
|1964||LY 2886721 hydrochloride||BACE 1 inhibitor||€105.00|
|1553||Nelfinavir mesylate||HIV-1 protease inhibitor||€95.00|
|2521||RO 4929097||Potent γ-secretase inhibitor (GSI) targeting Notch signaling in various tumor cells||€135.00|
|5007||Stem Cell 5i inhibitor Set||Set of five inhibitors for neural differentiation of human pluripotent stem cells.||€240.00|
|5006||Stem Cell CSD inhibitor Set||Set of CHIR 99021, SU5402, and DAPT, inhibitors of GSK-3, FGFR, and γ-secretase, resp.||€155.00|