Preferred Label : IRE1 RNase Inhibitor ORIN1001;
NCIt synonyms : Inositol-Requiring Enzyme 1 RNase Inhibitor ORIN1001;
NCIt related terms : MKC-8866;
NCIt definition : An orally bioavailable inhibitor of the serine/threonine-protein kinase/endoribonuclease
inositol-requiring enzyme 1 (inositol-requiring enzyme 1 alpha; IRE1), with potential
immunoactivating, chemosensitizing and antineoplastic activities. Upon oral administration,
IRE1 RNase inhibitor ORIN1001 targets and binds to the RNase domain of IRE1, thereby
inhibiting the activity of IRE1. This prevents activation of the IRE1/X-Box Binding
Protein 1 (XBP1) pathway, inhibits unfolded protein response (UPR) stress adaptation
and prevents the production of pro-tumorigenic factors. This may inhibit tumor growth
in which IRE1 is overactivated. In addition, ORIN1001 abrogates the immunosuppressive
tumor microenvironment (TME) through cytotoxic T-cell infiltration and depletion of
immunosuppressive myeloid-derived suppressor cells (MDSCs) in the TME. IRE1, an endoplasmic
reticulum (ER)-localized transmembrane protein containing an ER luminal stress-sensing
domain and a cytoplasmic facing RNase domain, acts as a key sensor for the UPR and
plays a key role in the response to and resolution of ER stress. IRE1 is involved
in both protein phosphorylation and mRNA processing and degradation in response to
ER stress-dependent signaling. IRE1 is frequently co-amplified with the MYC oncogene.;
UNII : 1NZ0YBP9HB;
CAS number : 1338934-59-0;
Molecule name : ORIN 1001; ORIN-1001; MKC-8866; MKC 8866;
NCI Metathesaurus CUI : CL1642406;
Origin ID : C176578;
UMLS CUI : C5447313;
Semantic type(s)
- concept_is_in_subset
- has_target
