Lestaurtinib
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 201730

CAS#: 111358-88-4

Description: 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.

Chemical Structure

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Lestaurtinib
CAS# 111358-88-4
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 201730
Name: Lestaurtinib
CAS#: 111358-88-4
Chemical Formula: C26H21N3O4
Exact Mass: 439.15
Molecular Weight: 439.471
Elemental Analysis: C, 71.06; H, 4.82; N, 9.56; O, 14.56

Price and Availability

Size Price Availability Quantity
5mg USD 350 2 weeks
10mg USD 650 2 Weeks
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Synonym: CEP701; CEP-701; CEP 701; KT5555; KT-5555; KT 5555; SP924; SP-924; SP 924. Lestaurtinib.

IUPAC/Chemical Name: (5S,6S,8R)-6-hydroxy-6-(hydroxymethyl)-5-methyl-7,8,14,15-tetrahydro-5H-16-oxa-4b,8a,14-triaza-5,8-methanodibenzo[b,h]cycloocta[jkl]cyclopenta[e]-as-indacen-13(6H)-one

InChi Key: UIARLYUEJFELEN-LROUJFHJSA-N

InChi Code: 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

SMILES Code: O=C1NCC(C2=C3N([C@]4(C)[C@](CO)(O)C[C@@]5([H])O4)C6=CC=CC=C62)=C1C7=C3N5C8=CC=CC=C78

Appearance: Solid powder

Purity: >98%

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Lestaurtinib (rINN, codenamed CEP-701) is a tyrosine kinase inhibitor structurally related to staurosporine, and is being developed by Cephalon. It is an inhibitor of FLT3, JAK2, TrkA, TrkB and TrkC. It is undergoing research for the treatment of acute myelogenous leukemia (AML) and myeloproliferative disorders. As of 2008, it was in Phase III clinical trials for AML and Phase II clinical trials for myeloproliferative disorders。   On 20 Jun 2009,  Cephalon, Inc. announced results from a pivotal clinical trial of lestaurtinib (CEP-701) in patients with relapsed acute myelogenous leukemia (AML) expressing FLT3 activating mutations. The study was designed to show the benefit of lestaurtinib in this patient population when given in sequence with standard induction chemotherapy compared to those treated with standard induction chemotherapy alone. An analysis of the study showed that patients who were treated with lestaurtinib showed similar rates of complete response but no increased benefit in overall survival, compared to those who received induction chemotherapy alone. "We are disappointed that this study with lestaurtinib did not demonstrate a benefit for this patient population but we remain committed to oncology clinical research and developing innovative therapies for life-threatening diseases," said Dr. Lesley Russell, Executive Vice President and Chief Medical Officer at Cephalon. For detail, see: medicinalnewstoday.com..    

Product Data:
Product Data
Instruction:
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Biological target: Lestaurtinib (CEP-701) is an orally active and selective RPTKs (receptor protein tyrosine kinase) inhibitor, competitively inhibits ATP binding to the TrkA/B/C domain.
In vitro activity: A detailed comparative analysis of different Janus kinase inhibitors in these quantitative assays and the subsequent characterization of additional activities demonstrated for the first time that the most potent Jak2 inhibitor in our study, CEP701, also targets Aurora kinases CEP701 shows a unique combination of both activities which is not found in other compounds also targeting Jak2. Reference: J Cell Mol Med. 2013 Feb;17(2):265-76. https://pubmed.ncbi.nlm.nih.gov/23301855/
In vivo activity: In vivo studies using the chick chorioallantoic membrane xenograft models demonstrated that treatment with Lestaurtinib resulted in a significant decrease in endpoint tumor volume and vascularity using power Doppler ultrasound imaging. Overall, this study provides evidence that Lestaurtinib is a potent antiproliferative agent with potential antiangiogenic activity that warrants further investigation as a targeted therapy for ATC. Reference: PLoS One. 2018 Nov 12;13(11):e0207152. https://pubmed.ncbi.nlm.nih.gov/30419054/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 5.0 11.38
DMF:PBS (pH 7.2) (1:20) 0.1 0.11
DMSO 32.3 73.54
Ethanol 11.0 25.01

Preparing Stock Solutions

The following data is based on the product molecular weight 439.47 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Gäbler K, Rolvering C, Kaczor J, Eulenfeld R, Méndez SÁ, Berchem G, Palissot V, Behrmann I, Haan C. Cooperative effects of Janus and Aurora kinase inhibition by CEP701 in cells expressing Jak2V617F. J Cell Mol Med. 2013 Feb;17(2):265-76. doi: 10.1111/jcmm.12005. Epub 2013 Jan 10. PMID: 23301855; PMCID: PMC3822589. 2. Diaz T, Navarro A, Ferrer G, Gel B, Gaya A, Artells R, Bellosillo B, Garcia-Garcia M, Serrano S, Martínez A, Monzo M. Lestaurtinib inhibition of the Jak/STAT signaling pathway in hodgkin lymphoma inhibits proliferation and induces apoptosis. PLoS One. 2011 Apr 20;6(4):e18856. doi: 10.1371/journal.pone.0018856. PMID: 21533094; PMCID: PMC3080386. 3. Pinto N, Prokopec SD, Vizeacoumar F, Searle K, Lowerison M, Ruicci KM, Yoo J, Fung K, MacNeil D, Lacefield JC, Leong HS, Mymryk JS, Barrett JW, Datti A, Boutros PC, Nichols AC. Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models. PLoS One. 2018 Nov 12;13(11):e0207152. doi: 10.1371/journal.pone.0207152. PMID: 30419054; PMCID: PMC6231667. 4. Iyer R, Evans AE, Qi X, Ho R, Minturn JE, Zhao H, Balamuth N, Maris JM, Brodeur GM. Lestaurtinib enhances the antitumor efficacy of chemotherapy in murine xenograft models of neuroblastoma. Clin Cancer Res. 2010 Mar 1;16(5):1478-85. doi: 10.1158/1078-0432.CCR-09-1531. Epub 2010 Feb 23. PMID: 20179224; PMCID: PMC2831131.
In vitro protocol: 1. Gäbler K, Rolvering C, Kaczor J, Eulenfeld R, Méndez SÁ, Berchem G, Palissot V, Behrmann I, Haan C. Cooperative effects of Janus and Aurora kinase inhibition by CEP701 in cells expressing Jak2V617F. J Cell Mol Med. 2013 Feb;17(2):265-76. doi: 10.1111/jcmm.12005. Epub 2013 Jan 10. PMID: 23301855; PMCID: PMC3822589. 2. Diaz T, Navarro A, Ferrer G, Gel B, Gaya A, Artells R, Bellosillo B, Garcia-Garcia M, Serrano S, Martínez A, Monzo M. Lestaurtinib inhibition of the Jak/STAT signaling pathway in hodgkin lymphoma inhibits proliferation and induces apoptosis. PLoS One. 2011 Apr 20;6(4):e18856. doi: 10.1371/journal.pone.0018856. PMID: 21533094; PMCID: PMC3080386.
In vivo protocol: 1. Pinto N, Prokopec SD, Vizeacoumar F, Searle K, Lowerison M, Ruicci KM, Yoo J, Fung K, MacNeil D, Lacefield JC, Leong HS, Mymryk JS, Barrett JW, Datti A, Boutros PC, Nichols AC. Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models. PLoS One. 2018 Nov 12;13(11):e0207152. doi: 10.1371/journal.pone.0207152. PMID: 30419054; PMCID: PMC6231667. 2. Iyer R, Evans AE, Qi X, Ho R, Minturn JE, Zhao H, Balamuth N, Maris JM, Brodeur GM. Lestaurtinib enhances the antitumor efficacy of chemotherapy in murine xenograft models of neuroblastoma. Clin Cancer Res. 2010 Mar 1;16(5):1478-85. doi: 10.1158/1078-0432.CCR-09-1531. Epub 2010 Feb 23. PMID: 20179224; PMCID: PMC2831131.

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 1: Iyer R, Evans AE, Qi X, Ho R, Minturn JE, Zhao H, Balamuth N, Maris JM, Brodeur GM. Lestaurtinib enhances the antitumor efficacy of chemotherapy in murine xenograft models of neuroblastoma. Clin Cancer Res. 2010 Mar 1;16(5):1478-85. Epub 2010 Feb 23. PubMed PMID: 20179224; PubMed Central PMCID: PMC2831131.

2: Shabbir M, Stuart R. Lestaurtinib, a multitargeted tyrosine kinase inhibitor: from bench to bedside. Expert Opin Investig Drugs. 2010 Mar;19(3):427-36. Review. PubMed PMID: 20141349.

3: Miller SC, Huang R, Sakamuru S, Shukla SJ, Attene-Ramos MS, Shinn P, Van Leer D, Leister W, Austin CP, Xia M. Identification of known drugs that act as inhibitors of NF-kappaB signaling and their mechanism of action. Biochem Pharmacol. 2010 May 1;79(9):1272-80. Epub 2010 Jan 11. PubMed PMID: 20067776; PubMed Central PMCID: PMC2834878.

4: Santos FP, Kantarjian HM, Jain N, Manshouri T, Thomas DA, Garcia-Manero G, Kennedy D, Estrov Z, Cortes J, Verstovsek S. Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Blood. 2010 Feb 11;115(6):1131-6. Epub 2009 Dec 11. PubMed PMID: 20008298.

5: Verstovsek S. Therapeutic potential of JAK2 inhibitors. Hematology Am Soc Hematol Educ Program. 2009:636-42. Review. PubMed PMID: 20008249.

6: Pratz KW, Sato T, Murphy KM, Stine A, Rajkhowa T, Levis M. FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML. Blood. 2010 Feb 18;115(7):1425-32. Epub 2009 Dec 10. PubMed PMID: 20007803; PubMed Central PMCID: PMC2826764.

7: Sanz M, Burnett A, Lo-Coco F, Löwenberg B. FLT3 inhibition as a targeted therapy for acute myeloid leukemia. Curr Opin Oncol. 2009 Nov;21(6):594-600. Review. PubMed PMID: 19684517.

8: Zarrinkar PP, Gunawardane RN, Cramer MD, Gardner MF, Brigham D, Belli B, Karaman MW, Pratz KW, Pallares G, Chao Q, Sprankle KG, Patel HK, Levis M, Armstrong RC, James J, Bhagwat SS. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood. 2009 Oct 1;114(14):2984-92. Epub 2009 Aug 4. PubMed PMID: 19654408; PubMed Central PMCID: PMC2756206.

9: Kumar C, Purandare AV, Lee FY, Lorenzi MV. Kinase drug discovery approaches in chronic myeloproliferative disorders. Oncogene. 2009 Jun 18;28(24):2305-13. Epub 2009 May 4. Review. PubMed PMID: 19421140.

10: Skarica M, Wang T, McCadden E, Kardian D, Calabresi PA, Small D, Whartenby KA. Signal transduction inhibition of APCs diminishes th17 and Th1 responses in experimental autoimmune encephalomyelitis. J Immunol. 2009 Apr 1;182(7):4192-9. PubMed PMID: 19299717.

11: Karp J. Future research directions for the treatment of AML. Clin Adv Hematol Oncol. 2008 Nov;6(11):8-10. PubMed PMID: 19205110.

12: Gore SD. New agents for the treatment of AML recent study findings. Clin Adv Hematol Oncol. 2008 Nov;6(11):6-8. PubMed PMID: 19205109.