Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T49639
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| Former ID |
TTDR00169
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| Target Name |
Heat shock protein 70
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| Gene Name |
HSF1
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| Synonyms |
Chaperone protein dnaK; HSP70; Heat shock 70 kDa protein; Molecular chaperone Hsp70; HSF1
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| Target Type |
Clinical Trial
|
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| 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] | |||||
| Diabetic neuropathy [ICD9: 250, 250.6, 356.0, 356.8; ICD10: E11.40] | |||||
| Diabetes [ICD9: 253.5, 588.1; ICD10: E23.2, N25.1] | |||||
| 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.
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| BioChemical Class |
HSF family
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| Target Validation |
T49639
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| UniProt ID | |||||
| Sequence |
MDLPVGPGAAGPSNVPAFLTKLWTLVSDPDTDALICWSPSGNSFHVFDQGQFAKEVLPKY
FKHNNMASFVRQLNMYGFRKVVHIEQGGLVKPERDDTEFQHPCFLRGQEQLLENIKRKVT SVSTLKSEDIKIRQDSVTKLLTDVQLMKGKQECMDSKLLAMKHENEALWREVASLRQKHA QQQKVVNKLIQFLISLVQSNRILGVKRKIPLMLNDSGSAHSMPKYSRQFSLEHVHGSGPY SAPSPAYSSSSLYAPDAVASSGPIISDITELAPASPMASPGGSIDERPLSSSPLVRVKEE PPSPPQSPRVEEASPGRPSSVDTLLSPTALIDSILRESEPAPASVTALTDARGHTDTEGR PPSPPPTSTPEKCLSVACLDKNELSDHLDAMDSNLDNLQTMLSSHGFSVDTSALLDLFSP SVTVPDMSLPDLDSSLASIQELLSPQEPPRPPEAENSSPDSGKQLVHYTAQPLFLLDPGS VDTGSNDLPVLFELGEGSYFSEGDGFAEDPTISLLTGSEPPKAKDPTVS |
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| Structure |
2LDU; 1DKX; 1DKY; 1DKZ; 1Q5L; 2BPR; 2KHO; 3DPO; 3DPP
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| Drugs and Mode of Action | |||||
| Drug(s) | AEG-33773 | Drug Info | Phase 2 | Diabetic neuropathy | [1] |
| AG-858 | Drug Info | Phase 2 | Leukemia | [2] | |
| AG-707 | Drug Info | Phase 1 | Herpes simplex virus infection | [3] | |
| Enkastim-ev | Drug Info | Phase 1 | Cancer | [4] | |
| H-103 | Drug Info | Phase 1 | Metastasis | [5] | |
| Minnelide 001 | Drug Info | Phase 1 | Gastrointestinal cancers | [6] | |
| Bimoclomol | Drug Info | Discontinued in Phase 2 | Diabetes | [7] | |
| BRX-005 | Drug Info | Discontinued in Phase 2 | Amyotrophic lateral sclerosis | [8] | |
| NK-1001 | Drug Info | Discontinued in Phase 2 | Atrial fibrillation | [9] | |
| Inhibitor | AEG-33773 | Drug Info | [10] | ||
| ELLAGIC ACID | Drug Info | [11] | |||
| NSC-119910 | Drug Info | [11] | |||
| NSC-119911 | Drug Info | [11] | |||
| NSC-119913 | Drug Info | [11] | |||
| Modulator | AG-707 | Drug Info | [12] | ||
| Bimoclomol | Drug Info | [13] | |||
| BRX-005 | Drug Info | [14] | |||
| Enkastim-ev | Drug Info | ||||
| H-103 | Drug Info | [5] | |||
| Minnelide 001 | Drug Info | [15] | |||
| NK-1001 | Drug Info | [16] | |||
| Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
| TEP | EXP Info | ||||
| References | |||||
| REF 1 | ClinicalTrials.gov (NCT00891683) Safety and Efficacy of AEG33773 Versus Placebo in Patients With Painful Diabetic Peripheral Neuropathy. U.S. National Institutes of Health. | ||||
| REF 2 | ClinicalTrials.gov (NCT00058747) AG-858 in Patients Who Are Cytogenetically Positive After Treatment With Gleevec . U.S. National Institutes of Health. | ||||
| REF 3 | ClinicalTrials.gov (NCT00231049) Trial Evaluating Safety, Tolerability and Immune Response of AG-707. U.S. National Institutes of Health. | ||||
| REF 4 | Clinical pipeline report, company report or official report of Multimmune GmbH. | ||||
| REF 5 | A 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 6 | ClinicalTrials.gov (NCT01927965) Study of Minnelide in Patients With Advanced GI Tumors. U.S. National Institutes of Health. | ||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004241) | ||||
| REF 8 | Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects. Nat Med. 1997 Oct;3(10):1150-4. | ||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033456) | ||||
| REF 10 | Mitogen-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 11 | Bioorg 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 12 | A 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 13 | Bimoclomol elevates heat shock protein 70 and cytoprotects rat neonatal cardiomyocytes. Eur J Pharmacol. 2002 Jan 18;435(1):73-7. | ||||
| REF 14 | Cardiovascular effects of BRX-005 comparison to bimoclomol. Life Sci. 2000 Aug 25;67(14):1783-9. | ||||
| REF 15 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | ||||
| REF 16 | Novel therapeutic targets in the management of atrial fibrillation. Am J Cardiovasc Drugs. 2014 Dec;14(6):403-21. | ||||
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