6-Bromo-8-methoxy-2-methylimidazo[1,2-a]pyrazine cas 1782574-28-0

1. Basic Information
· CAS Number: 1782574-28-0
· Generic Name: Zipalertinib
· Development Code: CLN-081, TAS6417
· Chemical Name: N-(3-((5-Chloro-4-((2-(dimethylphosphoryl)phenyl)amino)pyrimidin-2-yl)amino)-5-fluorophenyl)acrylamide
· Molecular Formula: C₂₁H₁₉ClFN₅O₂P
· Target: Epidermal Growth Factor Receptor (EGFR)
2. Drug Types and Mechanisms of Action
Zipalertinib is an oral, highly effective and irreversible tyrosine kinase inhibitor (TKI).
Its core mechanism of operation is:
· Targeting EGFR exon 20 insertion mutations (Exon 20 Insertion Mutations, EGFR ex20ins): In non-small cell lung cancer (NSCLC), EGFR ex20ins is the third most common type of EGFR mutation, following the classic 19th exon deletion (Ex19del) and the 21st exon L858R mutation.
· High selectivity: Unlike earlier EGFR-TKIs (such as osimertinib), Zipalertinib is designed to have high selectivity for EGFR ex20ins mutations, while having relatively low inhibitory activity against the wild-type EGFR. This is crucial because excessive inhibition of the wild-type EGFR can lead to common and often serious side effects, such as rash and diarrhea. The "wide therapeutic window" characteristic of Zipalertinib enables a better balance between efficacy and safety.
3. Indications (Research and Development Background)
Zipalertinib is mainly used for patients with advanced or metastatic non-small cell lung cancer (NSCLC) who carry the EGFR exon 20 insertion mutation.
Before the emergence of new-generation drugs such as Zipalertinib, patients with this condition had poor responses to first-generation, second-generation, and even third-generation EGFR-TKIs (such as Gefitinib, Erlotinib, and Osimertinib), and their prognosis was very poor. Traditional chemotherapy was the main option, but its effect was limited. Therefore, the development of Zipalertinib was to meet this unmet clinical need.
4. Clinical Development Status and Data
· Development stage: Zipalertinib has completed the key Phase 1/2a clinical trial and has demonstrated encouraging efficacy and good tolerability.
· Key clinical data:
· Efficacy: In the clinical trial, for patients with EGFR ex20ins NSCLC who have undergone extensive prior treatment, Zipalertinib showed a high objective response rate (ORR, the proportion of patients with significant tumor shrinkage) and durable disease control.
· Safety: The most common treatment-related adverse events include rash and diarrhea, but most are grade 1-2 (mild to moderate), and the severity is typically lower than that of other EGFR-TKIs, which confirms its advantage in targeting wild-type EGFR with low activity.

Based on these positive clinical data, the developer of Zipalertinib, Cullinan Oncology, is actively advancing its subsequent clinical studies and has already communicated with the US FDA, aiming to expedite the approval of this drug for market.
5. Summary and Implications
In summary, CAS 1782574-28-0 (Zipalertinib/CLN-081) is:
· A precise targeted drug: Specifically designed for patients with refractory EGFR ex20ins NSCLC.
· An optimized new-generation TKI: Through meticulous molecular design, it achieves efficient inhibition of the mutant EGFR while reducing the inhibition of the wild-type EGFR, thereby maintaining efficacy while enhancing safety.
· An important treatment hope: It provides a new and promising treatment option for patients who previously had no effective targeted treatment choices, representing another significant advancement in the field of precision medicine for lung cancer.