Apoptosis
The number of cells in multicellular organism is tightly regulated. Not simply by controlling the rate of cell division, but also by controlling the rate of cell death. If cells are no longer needed, they commit suicide by activating an intracellular death program. This process is therefore called programmed cell death or apoptosis (from a Greek word meaning “falling off,” as leaves from a tree). The intrinsic apoptotic pathway occurs by the release of cytochrome c from mitochondria. The extrinsic apoptotic pathway is caused by the binding of death ligands, such as TNF (tumor necrosis factor), Fas, and TRAIL (TNF-related-apoptosis-inducing ligand), to their corresponding receptors. Although programmed cell death is involved in a number of key biological phenomena, aberrant apoptosis results in diverse human diseases [1].
The amount of apoptosis that occurs in developing and adult animal tissues is surprisingly large. In the developing vertebrate nervous system up to half or more of the nerve cells normally die soon after they are formed. In a healthy adult human, billions of cells die in the bone marrow and intestine every hour. Although this process seems remarkably wasteful -especially as the vast majority are perfectly healthy at the time they kill themselves- programmed cell death plays an important role during embryonic development, as hands and feet, for example, are sculpted by apoptosis: they start out as spadelike structures, and the individual digits separate only as the cells between them die. In other cases, cells die when the structure they form is no longer needed. When a tadpole changes into a frog, the cells in the tail die, and the tail, which is not needed in the frog, disappears. In many other cases, cell death helps regulate cell numbers. In the developing nervous system, for example, cell death adjusts the number of nerve cells to match the number of target cells that require innervation. In all these cases, the cells die by apoptosis as well[2].
[2] D.R. Williams et al. An apoptosis-inducing small molecule that binds to heat shock protein 70. Angew. Chem. Int. Ed. Engl. 2008, 47, 7466-7469.
[1] B. Alberts, A. Johnson, J. Lewis et al. Molecular Biology of the Cell. 4th edition. New York. Garland Science, 2002.
Axon ID | Name | Description | From price | |
---|---|---|---|---|
4218 | Carfilzomib | Irreversible proteasome inhibitor | Inquire | |
1798 | Eeyarestatin I | Inhibitor of endoplasmic reticulum associated protein degradation (ERAD) | €80.00 | |
3732 | HBX 41,108 | Inhibitor of deubiquitinase USP7 | €90.00 | |
3426 | IU1-47 | Potent and selective inhibitor deubiquitinase USP14 | €80.00 | |
3770 | KSQ-2479 | An allosteric, first-in-class USP1 (Ubiquitin Specific Protease 1) inhibitor | Inquire | |
2449 | LDN 57444 | Reversible, competitive inhibitor of UCH-L1 deubiquitinase | €95.00 | |
1869 | MG 132 | Inhibitor of 26S proteasome | €80.00 | |
2309 | ML 323 | Selective, reversible and potent inhibitor of the USP1–UAF1 deubiquitinase complex | €95.00 | |
2678 | ML364 | Inhibitor of the deubiquitinase USP2 | €125.00 | |
2556 | MLN2238 | Selective and reversible 20S proteasome inhibitor | €85.00 | |
2557 | MLN9708 | Citrate prodrug of MLN2238, selective and reversible 20S proteasome inhibitor | €95.00 | |
2565 | N106 | Activator of E1 ligase mediated SERCA2a SUMOylation | €95.00 | |
2228 | NSC 687852 | Inhibitor of 19S regulatory-particle–associated deubiquitinases (DUBs: UCHL5 and USP14) | €90.00 | |
2011 | P 005091 | Inhibitor of deubiquitinase USP7 and USP47 | €95.00 | |
1906 | P 22077 | Inhibitor of deubiquitinase USP7 and USP47 | €95.00 | |
1953 | PRT 4165 | E3 Ubiquitin ligase Bmi1/Ring1A inhibitor | €70.00 | |
3210 | RA375 | Potent RPN13 inhibitor | €180.00 | |
1904 | SMER 3 | Inhibitor of an SCF family E3 Ubiquitin ligase | €90.00 | |
2512 | Spautin 1 | Inhibitor of USP10 and USP13 and Beclin1 related autophagy | €95.00 | |
2333 | TCID | Potent inhibitor of UCHL3 with >100-fold selectivity over UCHL1 | €80.00 | |
4121 | USP25/28 inhibitor AZ1 | Selective dual USP25/USP28 inhibitor | €110.00 | |
2991 | USP7-USP47 inhibitor | Selective inhibitor of deubiquitinase USP7 and USP47 | €90.00 | |
1779 | WP 1130 | Deubiquitinase Inhibitor | €95.00 |