WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201730
Description: Lesraurtinib, also known as CEP701; KT 5555; SP 924, is an orally bioavailable indolocarbazole derivative with antineoplastic properties. Lestaurtinib inhibits autophosphorylation of FMS-like tyrosine kinase 3 (FLT3), resulting in inhibition of FLT3 activity and induction of apoptosis in tumor cells that overexpress FLT3.
MedKoo Cat#: 201730
Chemical Formula: C26H21N3O4
Exact Mass: 439.15321
Molecular Weight: 439.46
Elemental Analysis: C, 71.06; H, 4.82; N, 9.56; O, 14.56
Synonym: CEP701; CEP-701; CEP 701; KT5555; KT-5555; KT 5555; SP924; SP-924; SP 924. Lestaurtinib.
IUPAC/Chemical Name: (5S,6S,8R)-6-hydroxy-6-(hydroxymethyl)-5-methyl-7,8,14,15-tetrahydro-5H-16-oxa-4b,8a,14-triaza-5,8-methanodibenzo[b,h]cycloocta[jkl]cyclopenta[e]-as-indacen-13(6H)-one
InChi Key: UIARLYUEJFELEN-LROUJFHJSA-N
InChi Code: InChI=1S/C26H21N3O4/c1-25-26(32,12-30)10-18(33-25)28-16-8-4-2-6-13(16)20-21-15(11-27-24(21)31)19-14-7-3-5-9-17(14)29(25)23(19)22(20)28/h2-9,18,30,32H,10-12H2,1H3,(H,27,31)/t18-,25+,26+/m1/s1
SMILES Code: O=C1NCC(C2=C3N([C@]4(C)[C@](CO)(O)C[C@@]5([H])O4)C6=CC=CC=C62)=C1C7=C3N5C8=CC=CC=C78
Lestaurtinib (rINN, codenamed CEP-701) is a tyrosine kinase inhibitor structurally related to staurosporine, and is being developed by Cephalon. It is an inhibitor of FLT3, JAK2, TrkA, TrkB and TrkC. It is undergoing research for the treatment of acute myelogenous leukemia (AML) and myeloproliferative disorders. As of 2008, it was in Phase III clinical trials for AML and Phase II clinical trials for myeloproliferative disorders。
On 20 Jun 2009, Cephalon, Inc. announced results from a pivotal clinical trial of lestaurtinib (CEP-701) in patients with relapsed acute myelogenous leukemia (AML) expressing FLT3 activating mutations. The study was designed to show the benefit of lestaurtinib in this patient population when given in sequence with standard induction chemotherapy compared to those treated with standard induction chemotherapy alone. An analysis of the study showed that patients who were treated with lestaurtinib showed similar rates of complete response but no increased benefit in overall survival, compared to those who received induction chemotherapy alone.
"We are disappointed that this study with lestaurtinib did not demonstrate a benefit for this patient population but we remain committed to oncology clinical research and developing innovative therapies for life-threatening diseases," said Dr. Lesley Russell, Executive Vice President and Chief Medical Officer at Cephalon. For detail, see: medicinalnewstoday.com..
1: Iyer R, Evans AE, Qi X, Ho R, Minturn JE, Zhao H, Balamuth N, Maris JM, Brodeur GM. Lestaurtinib enhances the antitumor efficacy of chemotherapy in murine xenograft models of neuroblastoma. Clin Cancer Res. 2010 Mar 1;16(5):1478-85. Epub 2010 Feb 23. PubMed PMID: 20179224; PubMed Central PMCID: PMC2831131.
2: Shabbir M, Stuart R. Lestaurtinib, a multitargeted tyrosine kinase inhibitor: from bench to bedside. Expert Opin Investig Drugs. 2010 Mar;19(3):427-36. Review. PubMed PMID: 20141349.
3: Miller SC, Huang R, Sakamuru S, Shukla SJ, Attene-Ramos MS, Shinn P, Van Leer D, Leister W, Austin CP, Xia M. Identification of known drugs that act as inhibitors of NF-kappaB signaling and their mechanism of action. Biochem Pharmacol. 2010 May 1;79(9):1272-80. Epub 2010 Jan 11. PubMed PMID: 20067776; PubMed Central PMCID: PMC2834878.
4: Santos FP, Kantarjian HM, Jain N, Manshouri T, Thomas DA, Garcia-Manero G, Kennedy D, Estrov Z, Cortes J, Verstovsek S. Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Blood. 2010 Feb 11;115(6):1131-6. Epub 2009 Dec 11. PubMed PMID: 20008298.
5: Verstovsek S. Therapeutic potential of JAK2 inhibitors. Hematology Am Soc Hematol Educ Program. 2009:636-42. Review. PubMed PMID: 20008249.
6: Pratz KW, Sato T, Murphy KM, Stine A, Rajkhowa T, Levis M. FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML. Blood. 2010 Feb 18;115(7):1425-32. Epub 2009 Dec 10. PubMed PMID: 20007803; PubMed Central PMCID: PMC2826764.
7: Sanz M, Burnett A, Lo-Coco F, LÃ¶wenberg B. FLT3 inhibition as a targeted therapy for acute myeloid leukemia. Curr Opin Oncol. 2009 Nov;21(6):594-600. Review. PubMed PMID: 19684517.
8: Zarrinkar PP, Gunawardane RN, Cramer MD, Gardner MF, Brigham D, Belli B, Karaman MW, Pratz KW, Pallares G, Chao Q, Sprankle KG, Patel HK, Levis M, Armstrong RC, James J, Bhagwat SS. 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. Epub 2009 Aug 4. PubMed PMID: 19654408; PubMed Central PMCID: PMC2756206.
9: Kumar C, Purandare AV, Lee FY, Lorenzi MV. Kinase drug discovery approaches in chronic myeloproliferative disorders. Oncogene. 2009 Jun 18;28(24):2305-13. Epub 2009 May 4. Review. PubMed PMID: 19421140.
10: Skarica M, Wang T, McCadden E, Kardian D, Calabresi PA, Small D, Whartenby KA. Signal transduction inhibition of APCs diminishes th17 and Th1 responses in experimental autoimmune encephalomyelitis. J Immunol. 2009 Apr 1;182(7):4192-9. PubMed PMID: 19299717.
11: Karp J. Future research directions for the treatment of AML. Clin Adv Hematol Oncol. 2008 Nov;6(11):8-10. PubMed PMID: 19205110.
12: Gore SD. New agents for the treatment of AML recent study findings. Clin Adv Hematol Oncol. 2008 Nov;6(11):6-8. PubMed PMID: 19205109.