Olmutinib is an orally active, mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). It was developed primarily for the treatment of EGFR T790M mutation-positive non-small cell lung cancer (NSCLC). Olmutinib is also known by the development codes HM-61713 and BI-1482694.
Olmutinib is a synthetic small-molecule compound belonging to the thienopyrimidine-based EGFR inhibitor class. The active moiety has the molecular formula C₂₆H₂₆N₆O₂S and molecular weight 486.59 g/mol. FDA's Global Substance Registration System identifies olmutinib as an achiral chemical substance with no defined stereocenters.
Olmutinib contains a thieno[3,2-d]pyrimidine core, an anilino substituent containing a 4-methylpiperazine group, and an acrylamide moiety.
Its systematic chemical name is:
N-[3-[2-[4-(4-methylpiperazin-1-yl)anilino]thieno[3,2-d]pyrimidin-4-yl]oxyphenyl]prop-2-enamide.
Olmutinib is designed to preferentially inhibit mutant forms of EGFR, including the clinically important T790M resistance mutation. Inhibition of mutant EGFR signaling can suppress downstream proliferative signaling and promote death of susceptible EGFR-driven tumor cells.
Olmutinib was developed as a targeted anticancer therapy for patients with EGFR mutation-positive NSCLC, particularly tumors harboring the T790M EGFR resistance mutation. IUPHAR/BPS records approval of olmutinib in South Korea in 2016.
The compound is also relevant to:
Olmutinib has a calculated molecular weight of 486.59 g/mol, XlogP around 4.7, and topological polar surface area of approximately 111 Ų according to current PubChem calculations.
The molecule contains nitrogen-rich heterocyclic functionality and a thioether-containing fused heterocycle, contributing to its physicochemical and kinase-binding characteristics.
A particularly important CMS point is that olmutinib free base and olmutinib hydrochloride/dihydrochloride monohydrate should not be treated as identical API entries.
FDA GSRS separately identifies:
Therefore, if your physical product is olmutinib dihydrochloride monohydrate, the CMS molecular weight and formula should be changed accordingly.
Olmutinib as a small-molecule API can be evaluated using conventional pharmaceutical analytical techniques, including:
For a commercial API page, the actual approved batch specification or CoA should take precedence over literature values for assay and impurity acceptance criteria.
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.2% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |