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KRCA-0008 Suppresses ALK-positive Anaplastic Large-Cell Lymphoma Growth

KRCA-0008 Suppresses ALK-positive Anaplastic Large-Cell Lymphoma Growth

Jungjoong Hwang, Insuk Song, Kwangho Lee, Hyoung Rae Kim, Eun-Hye Hong, Jung Soon Hwang, Sung-Hoon Ahn, Jongkook Lee

Invest New Drugs. 2020 Jan 20.

PMID: 31956933

Abstract:

Anaplastic lymphoma kinase (ALK), which belongs to the insulin receptor tyrosine kinase superfamily, plays an important role in nervous system development. Due to chromosomal translocations, point mutations, and gene amplification, constitutively activated ALK has been implicated in a variety of human cancers, including anaplastic large-cell lymphoma (ALCL), non-small cell lung cancer, and neuroblastoma. We evaluated the anti-cancer activity of the ALK inhibitor KRCA-0008 using ALCL cell lines that express NPM (nucleophosmin)-ALK. KRCA-0008 strongly suppressed the proliferation and survival of NPM-ALK-positive ALCL cells. Additionally, it induced G0/G1 cell cycle arrest and apoptosis by blocking downstream signals including STAT3, Akt, and ERK1/2. Tumor growth was strongly suppressed in mice inoculated with Karpas-299 tumor xenografts and orally treated with KRCA-0008 (50 mg/kg, BID) for 2 weeks. Our results suggest that KRCA-0008 will be useful in further investigations of ALK signaling, and may provide therapeutic opportunities for NPM-ALK-positive ALCL patients.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1472795202	KRCA-0008		1472795-20-2	Price

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