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Targeting endogenous inhibitors of apoptosis: Opportunities for the treatment of cancer, stroke and MS Product Image

Targeting endogenous inhibitors of apoptosis: Opportunities for the treatment of cancer, stroke and MS

  • Published: January 2003
  • 65 pages
  • Lead Discovery

It is now well established that cellular suicide (apoptosis or programmed cell death) is central to a number of physiological cellular processes and is essential in the maintenance of homeostasis and survival of multicellular organisms. Equally, or perhaps even more important is the role of apoptosis in the pathogenesis of many human diseases.

Apoptosis stimulators have emerged as key targets for the control of cancer. This therapeutic class has, however, remained predominantly experimental and of the 100 or so molecules in development as apoptosis agonists, approaching 70% of these remain in preclinical development. The low rate of clinical entry associated with these molecules is related to lack of specificity, low efficacy and/or susceptibility to drug resistance. These issues are being addressed as our understanding of the field evolves, and as a result, the identification and exploitation of new targets remains a considerable focus of attention - indeed the number of pro-apoptotic molecules in preclinical development has risen by about 10-fold since 1995

From a molecular point of view this field concentrated heavily on the caspases and endogenous inhibitors of apoptosis, READ MORE >

Background
Apoptosis
A general introduction to apoptosis
The "Inhibitor of Apoptosis Proteins" family
Characterization of IAP family members
BIRC1 (Neuronal apoptosis inhibitory protein; NAIP)
BIRC2 (API1; HIAP2; cIAP1; MIHB)
BIRC3 (API2; HIAP1; cIAP2; MIHC)
BIRC4 (XIAP; API3; MIHA; ILP)
BIRC5 (Survivin; API4; TLAP)
BIRC6 (Apollon; BRUCE)
BIRC7 (MLIAP; KIAP; Livin)
BIRC8: (ILP-2; TIAP)
Mechanism of IAP action
Regulation of IAPs
Transcriptional/post-transcriptional control
Post-translational control
IAP regulatory proteins
IAPs in disease
The IAP family as a target for cancer therapy
Epidemiology and treatment options of major cancers
The role of IAPs in the development of cancer
Inhibition of IAPs for the treatment of cancer - strategies and therapeutic response
The IAP family as a target for stroke
Epidemiology and treatment options of stroke
The ischemic cascade
Contribution of apoptosis to the pathogenesis of stroke
The role of IAPs in stroke
Up-regulating IAPs for the treatment of stroke - strategies and therapeutic response
The IAP family as a target for multiple sclerosis
Epidemiology and treatment options of multiple sclerosis
The neuroimmunology of multiple sclerosis
Apoptosis failure as a pathophysiological feature of multiple sclerosis
Involvement of the IAP family in angiogenesis: Implications for both tumor progression and protection against ischemic disease
Market values
An overview of current development activity
Apoptosis stimulators
Trends in apoptosis stimulators
Apoptosis stimulators in development
Profiles of molecules in advanced development
arsenic trioxide
alitretinoin
alitretinoin
CDA-II
exisulind
rubitecan
p53 gene therapy
fenretinide
oblimersen sodium
Unnamed molecules
SDX-101
ceflatonin
Ro-31-7453
epothilone B
brostallicin
T-138067
MX6
CP-461
TLK-286
apomine
hCG
retinoic acid
Urocidin
PCK-3145
LGD-1550
kahalalide F
IL-13-PE38
apolizumab
alvocidib
indisulam
combretastatin A-4
Profiles of IAP-related molecules
HIAP-1 antisense
XIAP inhibitors
AEG-161
Apoptosis inhibitors
Trends in apoptosis inhibitors
Apoptosis inhibitors in development
Profiles of molecules in advanced development
PBI-1402
CPI-1189
DP-b99
IDN-6556
TCH-346
Profiles of IAP-related molecules
IAP gene therapy
Recent patent activity surrounding the IAP family
Strategic summary

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