MKC8866

Chemical Information
IRE1 RNase Inhibitor ORIN1001 is 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.
| CAS Number | 1338934-59-0 |
| PubChem CID | 89542346 |
| IUPAC Name | 7-hydroxy-6-methoxy-4-methyl-3-(2-morpholin-4-yl-2-oxoethyl)-2-oxochromene-8-carbaldehyde |
| Molecular Formula | C18H19NO7 |
| Molecular Weight | 361.3 |
| XLogP | 0.5 |
| Topological Polar Surface Area | 102 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 26 |
| Formal Charge | 0 |
| Complexity | 611 |
| Property | Value |
|---|---|
| Molecular Weight | 361.3 |
| XLogP3 | 0.5 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 4 |
| Exact Mass | 361.11615195 |
| Monoisotopic Mass | 361.11615195 |
| Topological Polar Surface Area | 102 Ų |
| Heavy Atom Count | 26 |
| Formal Charge | 0 |
| Complexity | 611 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Covalently-Bonded Unit Count | 1 |
| Compound Is Canonicalized | Yes |
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