Lestaurtinib

Description

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

Chemical Properties

Lestaurtinib is Off-White Solid

Uses

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

Uses

It 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-interacting?protein kinase?4 (RIPK4)
• as an FMS-like tyrosine kinase 3 (FLT3) inhibitor-gold nanoparticle conjugate to study its effects on acute myeloid leukemia

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) Levis?et al. (2003),?Novel FLT3 tyrosine kinase inhibitors; Expert Opin. Investig. Drugs,?12?1951 2) Chen?et al.?(2005),?FLT3/ITD Mutation Signaling Includes Suppression of SHP-1; J. Biol. Chem.,?280?5361 3) Strock?et al. (2003),?CEP-701 and CEP-751 Inhibit Constitutively Activated RET Tyrosine Kinase Activity and Block Medullary Thyroid Carcinoma Cell Growth; Cancer Res.,?63?5559 4) Hexner?et al. (2008),?Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders; Blood,?111?5663 5) Ruggeri?et al. (1999),?Role of neurotrophin-trk interactions in oncology: the anti-tumor efficacy of potent and selective trk tyrosine kinase inhibitors in pre-clinical tumor models; Curr. Med. Chem.,?6?845