Proteases (Aspartate)

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 cardiovascularinflammatoryneurodegenerativebacterial, 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 serinecysteine or threonine proteases (amino-terminal nucleophile hydrolases), or as asparticmetallo and glutamic proteases (with glutamic proteases being the only subtype not found in mammals so far)[1]. 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[2].
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[3].

[1] Targeting proteases: successes, failures and future prospects. Boris Turk. Nature Reviews – Drug Discovery. Volume 5, 2006, 785-799.
[2] Proteases: Multifunctional Enzymes in Life and Disease. C. López-Otín, J.S. Bond. J. Biol. Chem. 2008, 283, 30433-30437.
[3] 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.

19 Item(s)

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Axon ID Name Description From price
1125 BACE-1 Inhibitor BACE 1 inhibitor €110.00
2957 BACE-2 Inhibitor Potent and highly selective BACE 2 inhibitor €140.00
2117 Begacestat Selective γ-secretase inhibitor (GSI) €85.00
1441 BMS 232632 Protease inhibitor €80.00
1753 Compound 120 Deuterated Protease inhibitor (see Axon 1441) €120.00
1484 DAPT γ-Secretase inhibitor €90.00
3137 Darunavir HIV-1 protease inhibitor €60.00
3138 Lopinavir HIV-1 protease inhibitor €80.00
2869 LX2343 BACE 1 inhibitor €125.00
2225 LY 2811376 The first orally available non-peptidic BACE 1 inhibitor €125.00
1964 LY 2886721 hydrochloride BACE 1 inhibitor €105.00
1553 Nelfinavir mesylate HIV-1 protease inhibitor €90.00
3139 Ritonavir HIV-1 protease inhibitor €50.00
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. €200.00
5006 Stem Cell CSD inhibitor Set Set of CHIR99021, SU5402, and DAPT, inhibitors of GSK-3, FGFR, and γ-secretase, resp. €140.00
4166 Verubecestat First-in-class, potent, orally bioavailable high-affinity BACE1 inhibitor  Recently added €80.00
1487 γ-Secretase Inhibitor BZ γ-Secretase inhibitor (GSI) €90.00
1488 γ-Secretase Inhibitor DBZ γ-Secretase inhibitor (GSI) €80.00

19 Item(s)

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