Apoptosis inductors

Other Fluorinated Antitumor Drugs in Development A number of totally synthetic fluorinated molecules are also in clinical development for cancer therapies. There are numerous inhibitors of kinases, some apoptosis inductors, and antifolates. 

Conversely, to the (5)-enantiomer, it does not inhibit COX enzymes, but it is an apoptosis inductor. It is also in phase III evaluation for treatment of Alzheimer dementia vide infra) Celebrex, another NS AID drug, is also being evaluated for the treatment of several cancers. 

T-138067 is a sulfamide apoptosis inductor developed as an antitumor (Phase II). It binds irreversibly to jS-tubulin. 

Very recently, (3-lactam antibiotics have been shown to offer neuroprotection by increasing glutamate transporters expression via gene activation [15] in addition, the discoveries of new biologically active (3-lactams such as cholesterol acyl transferase inhibitors [16-18], thrombin inhibitors [19], human cytomegalovirus protease inhibitors [20], matrix-metallo protease inhibitors [21], inhibitors of human leukocyte elastase (HLE) [22, 23] and cysteine protease [24, 25], and apoptosis inductors [26, 27] have provided much needed motivation for continuous development of new (3-lactam systems. 

Aplidine , Plitidepsin) PharmaMar Ascidian (apoptosis inductor) ... 

Fig. 7.3. Osteoclastogenesis after estrogen deficiency. Estrogen deprivation leads to an increase in the synthesis of RANKL for stromal/OB cells of the BM. This increase in the expression of RANKL leads to an increase in OCS. Estrogen deficiency also induces the synthesis and secretion of cytokines, such as IL-6 and M-CSF, that increase the number of preosteoclasts in the BM, and thus increases OCS. Nonetheless, certain cells of the immune system, such as monocytes and T-cells, intervene in the process when the supply of estrogens fails. These cells secrete IL-1 and TNF-a that are powerful inductors of OCS. When estrogens or agonists of estrogen receptors like raloxifene are administered, the synthesis and secretion of many of the mentioned cytokines diminish and the synthesis and liberation of OPG and TGF-/S are stimulated. These molecules inhibit OCS by inhibiting the RANKL/RANK signal pathway and by promoting osteoclast apoptosis...

Sulindac is a racemic sulfoxide. Its deoxygenated metabolite (i.e., a sulfide) induces apoptosis, probably through inhibition of PPAR (Peroxisome Proliferator-Activated Receptor) It is probably the reason why suhndac seems to protect against colorectal cancers. Indeed, sulindac inhibits colorectal tumor cell growth. One other metabolite of sulindac, the sulfone exulind, is an inductor of apoptosis, and is currently in Phase III clinical trials for treatment of tumors (Figure 8.3). 

Dehydrodidemnin B (Aplidin , Plitidepsin) This molecule is anti-proliferative by blocking the synthesis of DNA of tumour cells by action on the first phase, Gl, of the cellular cycle (Weinberg, 1996). It is also an inductor of the non-programmed death of tumour cells (apoptosis). This compound could become a useful drug against prostate and bladder cancers, and against gastric tumours. 

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