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XMD8-92 Inhibits Pancreatic Tumor Xenograft Growth via a DCLK1-dependent Mechanism

XMD8-92 Inhibits Pancreatic Tumor Xenograft Growth via a DCLK1-dependent Mechanism

Sripathi M Sureban, Randal May, Nathaniel Weygant, Dongfeng Qu, Parthasarathy Chandrakesan, Eddie Bannerman-Menson, Naushad Ali, Panayotis Pantazis, Christoph B Westphalen, Timothy C Wang, Courtney W Houchen

Cancer Lett. 2014 Aug 28;351(1):151-61.

PMID: 24880079

Abstract:

XMD8-92 is a kinase inhibitor with anti-cancer activity against lung and cervical cancers, but its effect on pancreatic ductal adenocarcinoma (PDAC) remains unknown. Doublecortin-like kinase1 (DCLK1) is upregulated in various cancers including PDAC. In this study, we showed that XMD8-92 inhibits AsPC-1 cancer cell proliferation and tumor xenograft growth. XMD8-92 treated tumors demonstrated significant downregulation of DCLK1 and several of its downstream targets (including c-MYC, KRAS, NOTCH1, ZEB1, ZEB2, SNAIL, SLUG, OCT4, SOX2, NANOG, KLF4, LIN28, VEGFR1, and VEGFR2) via upregulation of tumor suppressor miRNAs let-7a, miR-144, miR-200a-c, and miR-143/145; it did not however affect BMK1 downstream genes p21 and p53. These data taken together suggest that XMD8-92 treatment results in inhibition of DCLK1 and downstream oncogenic pathways (EMT, pluripotency, angiogenesis and anti-apoptotic), and is a promising chemotherapeutic agent against PDAC.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1234480502	XMD8-92		1234480-50-2	Price

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