2. Academic Validation
  3. Discovery of N-{2-Methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}-N'-[2-(propane-2-sulfonyl)phenyl]-1,3,5-triazine-2,4-diamine (ASP3026), a Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor

Discovery of N-{2-Methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}-N'-[2-(propane-2-sulfonyl)phenyl]-1,3,5-triazine-2,4-diamine (ASP3026), a Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor

  • Chem Pharm Bull (Tokyo). 2018;66(3):251-262. doi: 10.1248/cpb.c17-00784.
Kazuhiko Iikubo 1,  Yutaka Kondoh 1,  Itsuro Shimada 1,  Takahiro Matsuya 1,  Kenichi Mori 1,  Yoko Ueno 1,  Minoru Okada 1
Affiliations

Affiliation

  • 1 Drug Discovery Research, Astellas Pharma Inc.
PMID: 29491259 DOI: 10.1248/cpb.c17-00784
Abstract

Anaplastic lymphoma kinase (ALK) is a validated therapeutic target for treating echinoderm microtubule-associated protein-like 4 (EML4)-ALK positive non-small cell lung Cancer (NSCLC). We synthesized a series of 1,3,5-triazine derivatives and identified ASP3026 (14a) as a potent and selective ALK inhibitor. In mice xenografted with NCI-H2228 cells expressing EML4-ALK, once-daily oral administration of 14a demonstrated dose-dependent antitumor activity. Here, syntheses and structure-activity relationship (SAR) studies of 1,3,5-triazine derivatives are described.

Keywords

1,3,5-triazine; anaplastic lymphoma kinase; echinoderm microtubule-associated protein-like 4; non-small cell lung cancer.

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