111358-88-4 Usage
Description
Lestaurtinib, also known as CEP-701, is a potent and selective FMS-like tyrosine kinase 3 (FLT3) inhibitor with an IC50 of 2 nM. It is an off-white solid that exhibits inhibitory effects on various signaling pathways and has been found to be effective in suppressing the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Lestaurtinib also acts as a potent Trk inhibitor and has cell permeable properties.
Uses
Used in Oncology:
Lestaurtinib is used as an anticancer agent for the treatment of pancreatic cancer and acute myelogenous leukemia (AML). It modulates several oncological signaling pathways, including FLT3, RET, and JAK2/STAT5, exerting inhibitory effects on tumor growth and progression.
Used in Research Applications:
Lestaurtinib is 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. It is also used as a supplement in reservoir solution for co-crystallization studies with human receptor-interacting protein kinase 4 (RIPK4) and as an FLT3 inhibitor-gold nanoparticle conjugate to study its effects on acute myeloid leukemia.
Used in Drug Delivery Systems:
Lestaurtinib has been explored for its potential in drug delivery systems, with various organic and metallic nanoparticles employed as carriers for its delivery. This aims to improve the bioavailability and therapeutic outcomes of Lestaurtinib in cancer treatment.
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.
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
Check Digit Verification of cas no
The CAS Registry Mumber 111358-88-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,1,1,3,5 and 8 respectively; the second part has 2 digits, 8 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 111358-88:
(8*1)+(7*1)+(6*1)+(5*3)+(4*5)+(3*8)+(2*8)+(1*8)=104
104 % 10 = 4
So 111358-88-4 is a valid CAS Registry Number.
InChI:InChI=1/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-/m0/s1
111358-88-4Relevant articles and documents
Synthesis and kinase inhibitory activity of 3′-(S)-epi-K-252a
Gingrich, Diane E.,Hudkins, Robert L.
, p. 2829 - 2831 (2002)
The 3′-epi diastereomer of K-252a was synthesized with the goal of evaluating the stereochemical requirements of the 3′-sugar alcohol on kinase inhibitory activity. Inverting the 3′-alcohol resulted in a 20 nM inhibitor of VEGFR2 and a 1 nM inhibitor of TrkA tyrosine kinase.
Synthesis, modeling, and in vitro activity of (3′S)-epi-K-252a analogues. Elucidating the stereochemical requirements of the 3′-sugar alcohol on trkA tyrosine kinase activity
Gingrich, Diane E.,Yang, Shi X.,Gessner, George W.,Angeles, Thelma S.,Hudkins, Robert L.
, p. 3776 - 3783 (2007/10/03)
Utilizing our recently published semisynthetic approach to the (3′S)-K-252a diastereomer, we report the first synthesis of the (3′R)-10 diastereomer and a set of related epimers, with the goal of defining the Stereochemical role of the 3′-sugar hydroxyl g
