MedKoo product information:

AZM-475271 

Description of AZM475271: AZM475271 is orally Src tyrosine kinase inhibitor with potential anticancer  and antimetastatic activities. Chemical structurally, AZM-475271 is the 4-amino-quinazoline based anticancer agent. AZM475271 remarkably inhibits growth and metastasis of orthotopically implanted human pancreatic carcinoma cells in nude mice. AZM475271 suppresses tumor growth and metastasis in vitro and in vivo potentially by anti-angiogenic mechanisms.

Current developer:    AstraZeneca.

Treatment with AZM475271 alone reduced the primary pancreatic tumor volume by approximately 40%, whereas AZM475271 plus gemcitabine reduced tumor volume by 90%. Furthermore, treatment with AZM475271 and gemcitabine significantly reduced metastasis: none of eight animals who received the combination treatment had lymph node or liver metastases, compared with five of five and three of five animals, respectively, in the control group (P = 0.001). Src inhibition by AZM475271 (alone or with gemcitabine) was associated with significantly reduced tumor cell proliferation, decreased tumor microvessel density, and increased apoptosis in vivo. Moreover, these effects were all significantly increased when gemcitabine was combined with AZM475271 compared with gemcitabine alone. CONCLUSIONS: Src inhibition by AZM475271, either alone or in combination with gemcitabine, demonstrated significant antitumor and antimetastatic activity in an orthotopic nude mouse model for human pancreatic cancer. The combination of AZM475271 with gemcitabine sensitized tumor cells to the cytotoxic effect of gemcitabine. [source: Clin Cancer Res. 2004 Dec 1;10(23):8028-36.]

 1: Ischenko I, Seeliger H, Camaj P, Kleespies A, Guba M, Eichhorn ME, Jauch KW, Bruns CJ. Src tyrosine kinase inhibition suppresses lymphangiogenesis in vitro and in vivo. Curr Cancer Drug Targets. 2010 Aug;10(5):546-53. PubMed PMID: 20370688.

2: Ischenko I, Guba M, Yezhelyev M, Papyan A, Schmid G, Green T, Fennell M, Jauch KW, Bruns CJ. Effect of Src kinase inhibition on metastasis and tumor angiogenesis in human pancreatic cancer. Angiogenesis. 2007;10(3):167-82. Epub 2007 May 8. PubMed PMID: 17486419.

3: Yezhelyev MV, Koehl G, Guba M, Brabletz T, Jauch KW, Ryan A, Barge A, Green T, Fennell M, Bruns CJ. Inhibition of SRC tyrosine kinase as treatment for human pancreatic cancer growing orthotopically in nude mice. Clin Cancer Res. 2004 Dec 1;10(23):8028-36. PubMed PMID: 15585638.