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heat shock protein 90 beta family member 1

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Target id: 2904

Nomenclature: heat shock protein 90 beta family member 1

Abbreviated Name: HSP90B1

Family: Heat shock proteins

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 803 12q23.3 HSP90B1 heat shock protein 90 beta family member 1
Mouse - 802 10 43.05 cM Hsp90b1 heat shock protein 90, beta (Grp94), member 1
Rat - 804 7q13 Hsp90b1 heat shock protein 90 beta family member 1
Previous and Unofficial Names Click here for help
Endoplasmin | GRP-94 | heat shock protein 90 | heat shock protein 90, beta (Grp94), member 1 | HSP90B1
Database Links Click here for help
Alphafold P14625 (Hs), P08113 (Mm), Q66HD0 (Rn)
CATH/Gene3D 3.30.565.10
ChEMBL Target CHEMBL1075323 (Hs), CHEMBL3425396 (Mm)
Ensembl Gene ENSG00000166598 (Hs), ENSMUSG00000020048 (Mm), ENSRNOG00000026963 (Rn)
Entrez Gene 7184 (Hs), 22027 (Mm), 362862 (Rn)
Human Protein Atlas ENSG00000166598 (Hs)
KEGG Gene hsa:7184 (Hs), mmu:22027 (Mm), rno:362862 (Rn)
Pharos P14625 (Hs)
RefSeq Nucleotide NM_003299 (Hs), NM_011631 (Mm), NM_001012197 (Rn)
RefSeq Protein NP_003290 (Hs), NP_035761 (Mm), NP_001012197 (Rn)
UniProtKB P14625 (Hs), P08113 (Mm), Q66HD0 (Rn)
Wikipedia HSP90B1 (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
Grp94 inhibitor 54 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 8.7 pIC50 1
⤷ pIC50 8.7 (IC50 2x10-9 M) [1]
compound 18c [PMID: 25901531] Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 6.7 pIC50 2
⤷ pIC50 6.7 (IC50 2.2x10-7 M) [2]
semapimod Small molecule or natural product Primary target of this compound Hs Inhibition 6.4 – 6.7 pIC50 7
⤷ pIC50 6.4 – 6.7 (IC50 4x10-7 – 2x10-7 M) [7]
Immunopharmacology Comments
HSP90B1 is an endoplasmic reticulum chaperone required for proper folding and cell surface export of newly synthesized Toll-like receptor and integrin (CD11a, CD18 and CD49d) proteins. In its absence TLR responses are ablated, and there is no innate response to microbial stimuli [4].[9]. HSP90B1 binding ligands which inhibit its association with other proteins are being investigated as anti-inflammatory agents (e.g. semapimod). HSP90B1-based autologous protein complexes isolated from cancer cells (e.g. vitespen [8], in Phase 3 clinical trial [5]) are under scrutiny as potential anti-cancer vaccine immunotherapeutics [3,6].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Antigen presentation
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling

References

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1. Jiang F, Guo AP, Xu JC, You QD, Xu XL. (2018) Discovery of a Potent Grp94 Selective Inhibitor with Anti-Inflammatory Efficacy in a Mouse Model of Ulcerative Colitis. J Med Chem, 61 (21): 9513-9533. [PMID:30351001]

2. Patel HJ, Patel PD, Ochiana SO, Yan P, Sun W, Patel MR, Shah SK, Tramentozzi E, Brooks J, Bolaender A et al.. (2015) Structure-activity relationship in a purine-scaffold compound series with selectivity for the endoplasmic reticulum Hsp90 paralog Grp94. J Med Chem, 58 (9): 3922-43. [PMID:25901531]

3. Randazzo M, Terness P, Opelz G, Kleist C. (2012) Active-specific immunotherapy of human cancers with the heat shock protein Gp96-revisited. Int J Cancer, 130 (10): 2219-31. [PMID:22052568]

4. Randow F, Seed B. (2001) Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability. Nat Cell Biol, 3 (10): 891-6. [PMID:11584270]

5. Testori A, Richards J, Whitman E, Mann GB, Lutzky J, Camacho L, Parmiani G, Tosti G, Kirkwood JM, Hoos A et al.. (2008) Phase III comparison of vitespen, an autologous tumor-derived heat shock protein gp96 peptide complex vaccine, with physician's choice of treatment for stage IV melanoma: the C-100-21 Study Group. J Clin Oncol, 26 (6): 955-62. [PMID:18281670]

6. Tosti G, Cocorocchio E, Pennacchioli E, Ferrucci PF, Testori A, Martinoli C. (2014) Heat-shock proteins-based immunotherapy for advanced melanoma in the era of target therapies and immunomodulating agents. Expert Opin Biol Ther, 14 (7): 955-67. [PMID:24670226]

7. Wang J, Grishin AV, Ford HR. (2016) Experimental Anti-Inflammatory Drug Semapimod Inhibits TLR Signaling by Targeting the TLR Chaperone gp96. J Immunol, 196 (12): 5130-7. [PMID:27194788]

8. Wood CG, Mulders P. (2009) Vitespen: a preclinical and clinical review. Future Oncol, 5 (6): 763-74. [PMID:19663726]

9. Yang Y, Liu B, Dai J, Srivastava PK, Zammit DJ, Lefrançois L, Li Z. (2007) Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages. Immunity, 26 (2): 215-26. [PMID:17275357]

How to cite this page

Heat shock proteins: heat shock protein 90 beta family member 1. Last modified on 29/10/2018. Accessed on 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2904.