Target Information

Target General Infomation
Target ID
T49639
Former ID
TTDR00169
Target Name
Heat shock protein 70
Gene Name
HSF1
Synonyms
Chaperone protein dnaK; HSP70; Heat shock 70 kDa protein; Molecular chaperone Hsp70; HSF1
Target Type
Clinical Trial
Disease Atrial fibrillation [ICD9: 272, 427.31; ICD10: E78, I48]
Amyotrophic lateral sclerosis [ICD9: 335.2; ICD10: G12.2]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Diabetes [ICD9: 253.5, 588.1; ICD10: E23.2, N25.1]
Diabetic neuropathy [ICD9: 250, 250.6, 356.0, 356.8; ICD10: E11.40]
Gastrointestinal cancers [ICD9: 150-159; ICD10: C15-C26]
Herpes simplex virus infection [ICD9: 54; ICD10: B00]
Leukemia [ICD9: 208.9; ICD10: C90-C95]
Metastasis [ICD10: C00-C97]
Function
Plays an essential role in the initiation of phage lambda dna replication, where it acts in an atp-dependent fashion with the dnaj protein to release lambda o and p proteins from the preprimosomal complex. Dnak is also involved in chromosomaldna replication.
BioChemical Class
HSF family
Target Validation
T49639
UniProt ID
Q00613
Sequence
MDLPVGPGAAGPSNVPAFLTKLWTLVSDPDTDALICWSPSGNSFHVFDQGQFAKEVLPKY
FKHNNMASFVRQLNMYGFRKVVHIEQGGLVKPERDDTEFQHPCFLRGQEQLLENIKRKVT
SVSTLKSEDIKIRQDSVTKLLTDVQLMKGKQECMDSKLLAMKHENEALWREVASLRQKHA
QQQKVVNKLIQFLISLVQSNRILGVKRKIPLMLNDSGSAHSMPKYSRQFSLEHVHGSGPY
SAPSPAYSSSSLYAPDAVASSGPIISDITELAPASPMASPGGSIDERPLSSSPLVRVKEE
PPSPPQSPRVEEASPGRPSSVDTLLSPTALIDSILRESEPAPASVTALTDARGHTDTEGR
PPSPPPTSTPEKCLSVACLDKNELSDHLDAMDSNLDNLQTMLSSHGFSVDTSALLDLFSP
SVTVPDMSLPDLDSSLASIQELLSPQEPPRPPEAENSSPDSGKQLVHYTAQPLFLLDPGS
VDTGSNDLPVLFELGEGSYFSEGDGFAEDPTISLLTGSEPPKAKDPTVS
Structure
2LDU; 1DKX; 1DKY; 1DKZ; 1Q5L; 2BPR; 2KHO; 3DPO; 3DPP
Drugs and Mode of Action
Drug(s) AEG-33773 Drug Info Phase 2 Diabetic neuropathy [522652]
AG-858 Drug Info Phase 2 Leukemia [521552]
AG-707 Drug Info Phase 1 Herpes simplex virus infection [521737]
Enkastim-ev Drug Info Phase 1 Cancer [551168]
H-103 Drug Info Phase 1 Metastasis [529874]
Minnelide 001 Drug Info Phase 1 Gastrointestinal cancers [524410]
Bimoclomol Drug Info Discontinued in Phase 2 Diabetes [545697]
BRX-005 Drug Info Discontinued in Phase 2 Amyotrophic lateral sclerosis [534488]
NK-1001 Drug Info Discontinued in Phase 2 Atrial fibrillation [549188]
Inhibitor AEG-33773 Drug Info [551193]
ELLAGIC ACID Drug Info [531262]
NSC-119910 Drug Info [531262]
NSC-119911 Drug Info [531262]
NSC-119913 Drug Info [531262]
Modulator AG-707 Drug Info [531564]
Bimoclomol Drug Info [526247]
BRX-005 Drug Info [525882]
Enkastim-ev Drug Info
H-103 Drug Info [529874]
Minnelide 001 Drug Info [1572591]
NK-1001 Drug Info [532907]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
References
Ref 521552ClinicalTrials.gov (NCT00058747) AG-858 in Patients Who Are Cytogenetically Positive After Treatment With Gleevec . U.S. National Institutes of Health.
Ref 521737ClinicalTrials.gov (NCT00231049) Trial Evaluating Safety, Tolerability and Immune Response of AG-707. U.S. National Institutes of Health.
Ref 522652ClinicalTrials.gov (NCT00891683) Safety and Efficacy of AEG33773 Versus Placebo in Patients With Painful Diabetic Peripheral Neuropathy. U.S. National Institutes of Health.
Ref 524410ClinicalTrials.gov (NCT01927965) Study of Minnelide in Patients With Advanced GI Tumors. U.S. National Institutes of Health.
Ref 529874A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients. Gene Ther. 2009 Mar;16(3):376-82.
Ref 534488Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects. Nat Med. 1997 Oct;3(10):1150-4.
Ref 545697Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004241)
Ref 549188Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033456)
Ref 551168Clinical pipeline report, company report or official report of Multimmune GmbH.
Ref
Ref 525882Cardiovascular effects of BRX-005 comparison to bimoclomol. Life Sci. 2000 Aug 25;67(14):1783-9.
Ref 526247Bimoclomol elevates heat shock protein 70 and cytoprotects rat neonatal cardiomyocytes. Eur J Pharmacol. 2002 Jan 18;435(1):73-7.
Ref 529874A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients. Gene Ther. 2009 Mar;16(3):376-82.
Ref 531262Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. Epub 2010 Oct 21.In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2).
Ref 531564A heat shock protein based polyvalent vaccine targeting HSV-2: CD4(+) and CD8(+) cellular immunity and protective efficacy. Vaccine. 2011 Nov 3;29(47):8530-41.
Ref 532907Novel therapeutic targets in the management of atrial fibrillation. Am J Cardiovasc Drugs. 2014 Dec;14(6):403-21.
Ref 544425Preparation of a Heat Shock Proteins 70-based Vaccine from DC-tumor fusion cells. Methods Mol Biol. 2011; 787: 255-265.
Ref 551193Mitogen-activated protein kinase kinase kinase 12 (MAP3K12; DLK); c-jun N-terminal kinase (JNK). SciBX 2(11); doi:10.1038/scibx.2009.462. March 19 2009
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

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