lestaurtinib   Click here for help

GtoPdb Ligand ID: 5672

Synonyms: CEP-701 | KT-5555 | SP924
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Lestaurtinib was identified as an inhibitor of the receptor tyrosine kinase (RTK) FLT3 (fms-related tyrosine kinase 3) with activity against leukemia cells in vitro and in vivo [2]. It has activity against other RTKs. A drug repurposing sceen for breast cancer has identified lestaurtinib as a promising agent which appears to sensitise BRCA mutant and wild type breast cancer cells to the effects of the Poly (ADP-ribose) polymerase 1 (PARP1) inhibitor AG14361 [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 1
Topological polar surface area 88.65
Molecular weight 439.15
XLogP 5.17
No. Lipinski's rules broken 1
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Canonical SMILES OCC1(O)CC2OC1(C)n1c3c4n2c2ccccc2c4c2c(c3c3c1cccc3)CNC2=O
Isomeric SMILES OC[C@@]1(O)C[C@H]2O[C@]1(C)n1c3c4n2c2ccccc2c4c2c(c3c3c1cccc3)CNC2=O
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
1. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011)
Comprehensive analysis of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
2. Levis M, Allebach J, Tse KF, Zheng R, Baldwin BR, Smith BD, Jones-Bolin S, Ruggeri B, Dionne C, Small D. (2002)
A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo.
Blood, 99 (11): 3885-91. [PMID:12010785]
3. Vazquez-Ortiz G, Chisholm C, Xu X, Lahusen TJ, Li C, Sakamuru S, Huang R, Thomas CJ, Xia M, Deng C. (2014)
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.
Breast Cancer Res, 16 (3): R67. [PMID:24962108]
4. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010)
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
Chem Biol, 17 (11): 1241-9. [PMID:21095574]
5. Zarrinkar PP, Gunawardane RN, Cramer MD, Gardner MF, Brigham D, Belli B, Karaman MW, Pratz KW, Pallares G, Chao Q et al.. (2009)
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).
Blood, 114 (14): 2984-92. [PMID:19654408]