Lestaurtinib

• CAT Number: R006622
• CAS Number: 111358-88-4
• Molecular Formula: C26H21N3O4
• Molecular Weight: 439.471
• Purity: ≥95%
• Target: Trk
• Solubility: Soluble in DMSO > 10 mM
• Storage: Desiccate at -20°C
• InChI: 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
• InChIKey: UIARLYUEJFELEN-LROUJFHJSA-N
• SMILES: CC12C(CC(O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)CNC6=O)(CO)O

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.

Reference

1:A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line chemotherapy for FLT3-mutated AML. Knapper S, Russell N, Gilkes A, Hills RK, Gale RE, Cavenagh JD, Jones G, Kjeldsen L, Grunwald MR, Thomas I, Konig H, Levis MJ, Burnett AK.Blood. 2017 Mar 2;129(9):1143-1154. doi: 10.1182/blood-2016-07-730648. Epub 2016 Nov 21. PMID: 27872058 2:Enhancing SHP-1 expression with 5-azacytidine may inhibit STAT3 activation and confer sensitivity in lestaurtinib (CEP-701)-resistant FLT3-ITD positive acute myeloid leukemia. Al-Jamal HA, Mat Jusoh SA, Hassan R, Johan MF.BMC Cancer. 2015 Nov 7;15:869. doi: 10.1186/s12885-015-1695-x. PMID: 26547689 Free PMC Article3:NGF-induced TrkA/CD44 association is involved in tumor aggressiveness and resistance to lestaurtinib. Aubert L, Guilbert M, Corbet C, Génot E, Adriaenssens E, Chassat T, Bertucci F, Daubon T, Magné N, Le Bourhis X, Toillon RA.Oncotarget. 2015;6(12):9807-19. PMID: 25840418 Free PMC Article4:Phase I dose escalation study of lestaurtinib in patients with myelofibrosis. Hexner EO, Mascarenhas J, Prchal J, Roboz GJ, Baer MR, Ritchie EK, Leibowitz D, Demakos EP, Miller C, Siuty J, Kleczko J, Price L, Jeschke G, Weinberg R, Basu T, Pahl HL, Orazi A, Najfeld V, Marchioli R, Goldberg JD, Silverman LR, Hoffman R.Leuk Lymphoma. 2015;56(9):2543-51. doi: 10.3109/10428194.2014.1001986. Epub 2015 Feb 20. PMID: 25563429 5:Crystal structures of PRK1 in complex with the clinical compounds lestaurtinib and tofacitinib reveal ligand induced conformational changes. Chamberlain P, Delker S, Pagarigan B, Mahmoudi A, Jackson P, Abbasian M, Muir J, Raheja N, Cathers B.PLoS One. 2014 Aug 11;9(8):e103638. doi: 10.1371/journal.pone.0103638. eCollection 2014. PMID: 25111382 Free PMC Article6:Drug repurposing screen identifies lestaurtinib amplifies the ability of the poly (ADP-ribose) polymerase 1 inhibitor AG14361 to kill breast cancer associated gene-1 mutant and wild type breast cancer cells. Vazquez-Ortiz G, Chisholm C, Xu X, Lahusen TJ, Li C, Sakamuru S, Huang R, Thomas CJ, Xia M, Deng C.Breast Cancer Res. 2014 Jun 24;16(3):R67. doi: 10.1186/bcr3682. PMID: 24962108 Free PMC Article7:Open-label study of oral CEP-701 (lestaurtinib) in patients with polycythaemia vera or essential thrombocythaemia with JAK2-V617F mutation. Hexner E, Roboz G, Hoffman R, Luger S, Mascarenhas J, Carroll M, Clementi R, Bensen-Kennedy D, Moliterno A.Br J Haematol. 2014 Jan;164(1):83-93. doi: 10.1111/bjh.12607. Epub 2013 Oct 28. PMID: 24903629 8:Lestaurtinib (CEP-701) attenuates /second hit/ kainic acid-induced seizures following early life hypoxic seizures. Obeid M, Rosenberg EC, Klein PM, Jensen FE.Epilepsy Res. 2014 May;108(4):806-10. doi: 10.1016/j.eplepsyres.2014.01.019. Epub 2014 Jan 31. PMID: 24582454 9:Induction of endoplasmic reticulum stress by sorafenib and activation of NF-κB by lestaurtinib as a novel resistance mechanism in Hodgkin lymphoma cell lines. Holz MS, Janning A, Renné C, Gattenlöhner S, Spieker T, Bräuninger A.Mol Cancer Ther. 2013 Feb;12(2):173-83. doi: 10.1158/1535-7163.MCT-12-0532. Epub 2012 Dec 13. PMID: 23243060 Free Article10:Lestaurtinib inhibits histone phosphorylation and androgen-dependent gene expression in prostate cancer cells. Köhler J, Erlenkamp G, Eberlin A, Rumpf T, Slynko I, Metzger E, Schüle R, Sippl W, Jung M.PLoS One. 2012;7(4):e34973. doi: 10.1371/journal.pone.0034973. Epub 2012 Apr 20. PMID: 22532837 Free PMC Article