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Targeting Hsp-90 Related Disease Entities for Therapeutic Development

  • Timothy Westlake
  • Mitchell Sun
  • Brandon C. Rosenblum
  • Zhengping Zhuang
  • Jared S. RosenblumEmail author
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 19)

Abstract

Heat shock protein 90 (HSP-90) has been identified in many disease processes including cancer, neurodegeneration, autoimmune diseases, and cancers. Great effort has been expended in the development of specific inhibitors of the N-terminal and C-terminal domains. Inhibitors of post-translational modification have also been developed. Herein, we explore the available inhibitors and those in development, discuss the relevant disease processes, and examine the pitfalls and promises of targeting HSP-90 for therapeutic intervention.

Keywords

Autoimmune disease Cancer Diabetes Heat shock proteins Neurodegeneration Therapeutics 

Abbreviations

17-AAG

Tanespimycin

ADME

absorption, distribution, metabolism, excretion

AKT

protein kinase B

b-RAF

B-Raf proto-oncogene

c-RAF

RAF proto-oncogene serine/threonine-protein kinase

CTD

C-terminal domain

DMAG

17-dimethylaminoethylamino-17-demethoxygeldanamycin

ER

endoplasmic reticulum

FKBP

FK506 binding protein

FLT

Fms-like tyrosine kinase

GBase

glucocerebrosidase

HDAC

histone deacetylase

HDACI

HDAC inhibitor

HER

human epidermal growth factor receptor

HIF

hypoxia inducible factor

HOP

HSP70-HSP90 organizaing protein

HSF

heat shock factor

HSP

heat shock protein

HTT

huntington protein

IKK

IkB kinase

JAK

Janus kinase

JNK

c-Jun N-terminal kinases

NF-kB

nuclear factor kappa light-chain enhancer of activated B cells

Nrf

nuclear factor erythroid 2-related factor

NTD

N-terminal domain

RAF

rapidly accelerated fibrosarcoma

RASGRP

RAS guanyl-releasing protein

SAHA

suberoyl anilide hydroxamic acid

STAT

signal transducer and activators of transcription

TPR

tetraotricopeptide repeat

VEGFR

vascular endothelial growth factor receptor

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Timothy Westlake
    • 1
  • Mitchell Sun
    • 1
    • 2
  • Brandon C. Rosenblum
    • 3
  • Zhengping Zhuang
    • 1
    • 3
  • Jared S. Rosenblum
    • 1
    Email author
  1. 1.Neuro-Oncology Branch, National Cancer InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Liberal Arts and SciencesUniversity of Illinois at ChicagoChicagoUSA
  3. 3.Surgical Neurology BranchNational Institute of Neurologic Disorders and StrokeBethesdaUSA

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