The executive guide to Heat Shock Proteins

Date: May 22, 2010
Pages: 268
Price:
US$ 515.00
Publisher: Espicom Business Intelligence
Report type: Strategic Report
Delivery: E-mail Delivery (PDF)
ID: E6C429EC6F1EN
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The executive guide to Heat Shock Proteins
The potential of Heat Shock Proteins (HSPs) has sparked considerable research and industry interest. Results from early phase studies are encouraging — are they the next big thing in cancer therapy?

Heat shock proteins have emerged as a promising target for cancer therapy and Espicom has identified a number of projects currently under clinical investigation that span both Phase I and II clinical trials. The majority of agents progressing through development are HSP90 inhibitors, with one HSP-based anticancer vaccine.

As a chaperone protein, HSP90 plays an important role in regulating the function and activity of numerous clients, or signalling, proteins that have been shown to be critical to cancer cell growth, proliferation and survival. The inhibition of HSP90 leads to degradation of these client proteins and the subsequent death of cancer cells dependent on their activity.

Many of HSP90’s client proteins are the targets of existing cancer drugs such as Roche’s Avastin (bevacizumab), Herceptin (trastuzumab) and Tarceva (erlotinib), Novartis’ Gleevec/Glivec (imatinib), Bayer’s Nexavar (sorafenib) and Pfizer’s Sutent (sunitinib). Inhibiting HSP90 offers the potential for treating cancers that have become resistant to targeted therapies such as the kinase inhibitors, for even kinase inhibitors are still dependent on HSP90 for their activity. The early HSP90 inhibitors, as analogues of geldanamycin, showed promising antitumour activity but were dogged by drug-related toxicities including hepatotoxicity, nephrotoxicity and pancreatitis, plus poor solubility, metabolic stability and difficulty in administration. Hence, few remain in clinical development.

The majority of HSP90 inhibitors now progressing through clinical trials are fully-synthetic compounds, with a number offering the advantage of oral availability. Assuming continued successful development, Biogen Idec’s synthetic, oral HSP90 inhibitor, BIIB021, looks set to be the first HSP inhibitor to reach the market in 2014, with potential future competition from other oral synthetic agents namely, Debio 0932, HSP990, MPC-3100, PF-04929113 and XL888, all currently progressing through Phase I trials.

This executive briefing provides a complete, fast, easy-to-read overview of the promising and topical Heat Shock Protein sector

EXECUTIVE SUMMARY

Introduction

What are Heat Shock Proteins?

Applications of Heat Shock Proteins

Heat Shock Protein Inhibitors
Heat Shock Protein 90
HSP90 in Cancer
HSP90 Inhibitors
HSP90 Inhibitor Targets
Research and Development Projects

Competitor Ratio Analysis
Competitor Ratio Analysis Criteria
Discontinued Development Projects

Alvespimycin
CNF1010
RP101
Tanespimycin
Summary


PRODUCTS UNDER PHASE II DEVELOPMENT

The following products are assessed by Mode of Action, Current Status, Proof of Concept/Clinical Data, Development Risks, Company Expertise, Competition within the Marketplace and Competitor Ratio Analysis

AUY922
BIIB021
Oncophage
Retaspimycin
STA-9090

PRODUCTS UNDER PHASE I DEVELOPMENT

Heat Shock Protein 90 Inhibitors

AT13387
Debio 0932
HSP990
IPI-493
KW-2478
MPC-3100
PF-04929113
XL888
Heat Shock Protein 27 Inhibitor

OGX-427
EXECUTIVE SUMMARY

Introduction
What are H eat Shock Proteins?
Ap lications of H eat Shock Proteins
  Heat Shock Protein Inhibitors
  Heat Shock Protein 90
    Hsp90 in Cancer
    Hsp90 Inhibitors
    Hsp90 Inhibitor Targets
Research and Development Projects
Competitor Ratio Analysis
  Competitor Ratio Analysis Criteria
Discontinued Development Projects
  Alvespimycin
  CNF 1010
  RP101
  Tanespimycin
Summary

PRODUCTS UNDER PHASE II DEVELOPMENT

AUY 922
  Mode of Action
  Current Status
  Proof of Concept/Clinical Data
  Development Risks
  Company Expertise
  Competition within the Market-place
  Competitor Ratio Analysis
BIIB021
  Mode of Action
  Current Status
  Proof of Concept/Clinical Data
  Development Risks
  Company Expertise
  Competition within the Market-place
  Competitor Ratio Analysis
Oncophage
  Mode of Action
  Current Status
  Proof of Concept/Clinical Data
  Development Risks
  Company Expertise
  Competition within the Market-place
  Competitor Ratio Analysis
Retaspimycin
  Mode of Action
  Current Status
  Proof of Concept/Clinical Data
  Development Risks
  Company Expertise
  Competition within the Market-place
  Competitor Ratio Analysis
STA -9090
  Mode of Action
  Current Status
  Proof of Concept/Clinical Data
  Development Risks
  Company Expertise
  Competition within the Market-place
  Competitor Ratio Analysis

PRODUCTS UNDER PHASE I DEVELOPMENT

Heat Shock Protein 90 Inhibi tors
  AT 13387
  Debio 0932
  HSP990
  IPI-493
  KW-2478
  MPC-3100
  PF-04929113
  XL888
Heat Shock Protein 27 Inhibi tor
  OGX-427
    Mode of Action
    Current Status
    Proof of Concept/Clinical Data
    Development Risks
    Company Expertise
    Competition within the Market-place

APPEND IX 1: PHASE TRANSITION PROBABILITY

APPEND IX 2: GLO SSARY

APPEND IX 3: BIBLIOGRAPHY


Journals
Other Sources

LIST OF TABLES

Agents Under Development Targeting Heat Shock Proteins
Timeline of Selected Development Projects
Key Drugs Analysed
Projects Discontinued from Development
Probability of Launch

LIST OF CHARTS

Role of Heat Shock Proteins Within a Cell
Role of Hsp90 with a cell
Pathways Affected by Hsp90
Competitor Ratio Analysis Scores by Product
AUY922 Mode of Action Within a Cancer Cell
STA-9090 Mode of Action in Cancer
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