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AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).
Blood. 2009 Oct 01; 114(14):2984-92.Blood

Abstract

Activating mutations in the receptor tyrosine kinase FLT3 are present in up to approximately 30% of acute myeloid leukemia (AML) patients, implicating FLT3 as a driver of the disease and therefore as a target for therapy. We report the characterization of AC220, a second-generation FLT3 inhibitor, and a comparison of AC220 with the first-generation FLT3 inhibitors CEP-701, MLN-518, PKC-412, sorafenib, and sunitinib. AC220 exhibits low nanomolar potency in biochemical and cellular assays and exceptional kinase selectivity, and in animal models is efficacious at doses as low as 1 mg/kg given orally once daily. The data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties is unique to AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for a clinical FLT3 inhibitor.

Authors+Show Affiliations

Ambit Biosciences, San Diego, CA 92121, USA. pzarrinkar@ambitbio.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19654408

Citation

Zarrinkar, Patrick P., et al. "AC220 Is a Uniquely Potent and Selective Inhibitor of FLT3 for the Treatment of Acute Myeloid Leukemia (AML)." Blood, vol. 114, no. 14, 2009, pp. 2984-92.
Zarrinkar PP, Gunawardane RN, Cramer MD, et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood. 2009;114(14):2984-92.
Zarrinkar, P. P., Gunawardane, R. N., Cramer, M. D., Gardner, M. F., Brigham, D., Belli, B., Karaman, M. W., Pratz, K. W., Pallares, G., Chao, Q., Sprankle, K. G., Patel, H. K., Levis, M., Armstrong, R. C., James, J., & Bhagwat, S. S. (2009). AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood, 114(14), 2984-92. https://doi.org/10.1182/blood-2009-05-222034
Zarrinkar PP, et al. AC220 Is a Uniquely Potent and Selective Inhibitor of FLT3 for the Treatment of Acute Myeloid Leukemia (AML). Blood. 2009 Oct 1;114(14):2984-92. PubMed PMID: 19654408.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). AU - Zarrinkar,Patrick P, AU - Gunawardane,Ruwanthi N, AU - Cramer,Merryl D, AU - Gardner,Michael F, AU - Brigham,Daniel, AU - Belli,Barbara, AU - Karaman,Mazen W, AU - Pratz,Keith W, AU - Pallares,Gabriel, AU - Chao,Qi, AU - Sprankle,Kelly G, AU - Patel,Hitesh K, AU - Levis,Mark, AU - Armstrong,Robert C, AU - James,Joyce, AU - Bhagwat,Shripad S, Y1 - 2009/08/04/ PY - 2009/8/6/entrez PY - 2009/8/6/pubmed PY - 2009/12/16/medline SP - 2984 EP - 92 JF - Blood JO - Blood VL - 114 IS - 14 N2 - Activating mutations in the receptor tyrosine kinase FLT3 are present in up to approximately 30% of acute myeloid leukemia (AML) patients, implicating FLT3 as a driver of the disease and therefore as a target for therapy. We report the characterization of AC220, a second-generation FLT3 inhibitor, and a comparison of AC220 with the first-generation FLT3 inhibitors CEP-701, MLN-518, PKC-412, sorafenib, and sunitinib. AC220 exhibits low nanomolar potency in biochemical and cellular assays and exceptional kinase selectivity, and in animal models is efficacious at doses as low as 1 mg/kg given orally once daily. The data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties is unique to AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for a clinical FLT3 inhibitor. SN - 1528-0020 UR - https://news.unboundmedicine.com/medline/citation/19654408/AC220_is_a_uniquely_potent_and_selective_inhibitor_of_FLT3_for_the_treatment_of_acute_myeloid_leukemia__AML__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)36836-1 DB - PRIME DP - Unbound Medicine ER -