Description

Lestaurtinib (111358-88-4) is a potent and selective FLT3 inhibitor (IC50= 2 nM).1,2Inhibits RET and RET phosphorylation in medullary thyroid carcinoma cells.3Suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders.4Potent Trk inhibitor.5Cell permeable.

Chemical Properties

Lestaurtinib is Off-White Solid

Uses

Lestaurtinib is used for the treatment of pancreatic cancer and acute myelogenous leukaemia (AML)

Uses

CEP-701 hydrate has been used as a tyrosine kinase inhibitor:

• to study its effects on early growth response protein (EGR) genes and nerve growth factor (NGF) stimulation in human epithelial cells
• as a supplement in reservoir solution for co-crystallization studies with human receptor-interactingprotein kinase4 (RIPK4)
• as an FMS-like tyrosine kinase 3 (FLT3) inhibitor-gold nanoparticle conjugate to study its effects on acute myeloid leukemia

Uses

It is used for the treatment of pancreatic cancer and acute myelogenous leukaemia (AML).

Definition

ChEBI: LSM-1231 is an indolocarbazole.

Biological Activity

Potent JAK2, FLT3 and TrkA inhibitor (IC 50 values are 0.9, 3 and < 25 nM respectively) that prevents STAT5 phosphorylation (IC 50 = 20 - 30 nM). Exhibits antiproliferative activity in vitro (IC 50 = 30 - 100 nM in HEL92.1.7 cells) and is effective against myeloproliferative disorders in vivo .

Biochem/physiol Actions

CEP-701 hydrate, also known as Lestaurtinib, can repress Janus kinase 2/signal transducer and activator of transcription 5 (JAK2/STAT5) signaling by the specific inhibition of JAK2.

storage

-20°C (desiccate)

References

[1] MARK LEVIS  Donald S. Novel FLT3 tyrosine kinase inhibitors.[J]. Expert opinion on investigational drugs, 2003, 12 12: 1951-1962. DOI:10.1517/13543784.12.12.1951
[2] PEILI CHEN. FLT3/ITD mutation signaling includes suppression of SHP-1.[J]. The Journal of Biological Chemistry, 2005, 280 7: 5361-5369. DOI:10.1074/jbc.m411974200
[3] CHRISTOPHER J STROCK. CEP-701 and CEP-751 inhibit constitutively activated RET tyrosine kinase activity and block medullary thyroid carcinoma cell growth.[J]. Cancer research, 2003: 5559-5563.
[4] ELIZABETH O HEXNER. Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders.[J]. Blood, 2008: 5663-5671. DOI:10.1182/blood-2007-04-083402
[5] B A RUGGERI. Role of neurotrophin-trk interactions in oncology: the anti-tumor efficacy of potent and selective trk tyrosine kinase inhibitors in pre-clinical tumor models.[J]. Current medicinal chemistry, 1999, 6 9: 845-857.