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| 5mg |
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Purity: ≥98%
Lestaurtinib (CEP-701; KT-5555; SP-924) is a novel, orally bioavailable and potent multi-kinase inhibitor with anticancer and anti-inflammatory activity. It acts by inhibiting Trk family of receptor tyrosine kinases with IC50s of 0.9, 3 and less than 25 nM for JAK2, FLT3 and TrkA, respectively. 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.
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| ln Vitro |
The proliferation of ATC cells is inhibited by lestaurtinib (0.01-10 µM; 72 h), with IC50 values of 0.21, 0.41, and 2.35 µM for KMH2, CAL62, and THJ-21T cells, respectively [1]. Lestaurtinib (0.125-4 µM; 24 h) totally inhibits pSTAT5 expression at 4 µM and decreases STAT5 phosphorylation in a concentration-dependent manner [1]. On WI-38, CAL62, and KMH2 cells, lestaurtinib (0.5 µM; 24 hours) exhibits anti-proliferative effects [1]. In CAL62 and KMH2 cells, lestaturtinib (4 μM; 24 hours) causes cell cycle arrest in the G2/M phase [1]. Lestaurtinib (30-300 nM; 48 hours) causes apoptosis in HL (Hodgkin lymphoma) cell lines in a dose-dependent manner [2]. At 300 nM, lestaurtinib (30, 100, and 300 nM; 1 hour) suppresses the phosphorylation of JAK2, STAT5, and STAT3 [2].
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| ln Vivo |
Lestaurtinib (20 mg/kg; subcutaneous injection; once daily on Saturday and Sunday and twice on Monday through Friday) significantly inhibits the growth of tumors in vivo [3].
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| Cell Assay |
Cell viability assay[1]
Cell Types: KMH2, CAL62, THJ-21T Cell Tested Concentrations: 0.01-10 µM Incubation Duration: 72 hrs (hours) Experimental Results: demonstrated good growth inhibitory activity, the IC50 of KMH2, CAL62 and THJ were 0.21 and 0.41 respectively and 2.35 µM for -21T cells, respectively. Cell proliferation assay[1] Cell Types: WI-38, CAL62 and KMH2 Cell Tested Concentrations: 0.5 µM Incubation Duration: 24 hrs (hours) Experimental Results: ATC cell proliferation was inhibited. Cell cycle analysis [1] Cell Types: CAL62 and KMH2 cells Tested Concentrations: 4 μM Incubation Duration: 24 h Experimental Results: Resulting in an increase in the number of cells in the G2/M phase and a decrease in the number of cells in the G1/M phase in the G0 and S phases (KMH2 cells are better than CAL62 cells more significant). Western Blot Analysis[1] Cell Types: CAL62 Cell Tested Concentrations: 0.125-4 µM Incubation Duration: 24 hrs (hours) Experimental Results: pSTAT5 was diminished in a concentration-dependent manner, with complete loss of pSTAT5 expression at 4 µM. Apoptosis analysis[2] Cell Types: L-428, L-12 |
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| Animal Protocol |
Animal/Disease Models: 4weeks old athymic nu/nu (nude) mice (SY5Y-TrkB xenograft model) [3].
Doses: 20 mg/kg Route of Administration: subcutaneous injection; twice (two times) daily (Monday to Friday) and one time/day (Saturday and Sunday); 3 weeks. Experimental Results: Dramatically slowed growth of SY5Y-TrkB xenografts. |
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| References |
[1]. Pinto N, et al. Lestaurtinib is a potent inhibitor of anaplastic thyroid cancer cell line models. PLoS One. 2018 Nov 12;13(11):e0207152.
[2]. Diaz T, et al. Lestaurtinib inhibition of the Jak/STAT signaling pathway in hodgkin lymphoma inhibits proliferation and induces apoptosis. PLoS One. 2011 Apr 20;6(4):e18856. [3]. Iyer R, et al. Lestaurtinib enhances the antitumor efficacy of chemotherapy in murine xenograft models of neuroblastoma. Clin Cancer Res. 2010 Mar 1;16(5):1478-85. [4]. Levis M, et al. A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo. Blood. 2002 Jun 1;99(11):3885-91. [5]. Shabbir M, et al. Lestaurtinib, a multitargeted tyrosine kinase inhibitor: from bench to bedside. Expert Opin Investig Drugs. 2010 Mar;19(3):427-36. [6]. Hexner EO, et al. Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood. 2008 Jun 15;111(12):5663-71. |
| Molecular Formula |
C26H21N3O4
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| Molecular Weight |
439.46
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| CAS # |
111358-88-4
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| SMILES |
O=C1NCC(C2=C3N([C@]4(C)[C@](CO)(O)C[C@@]5([H])O4)C6=CC=CC=C62)=C1C7=C3N5C8=CC=CC=C78
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| InChi Key |
UIARLYUEJFELEN-LROUJFHJSA-N
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| 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
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| 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
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| Synonyms |
CEP701; KT 5555; SP924; CEP-701; KT-5555; SP-924; CEP 701; KT5555; SP 924.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~113.78 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.69 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2755 mL | 11.3776 mL | 22.7552 mL | |
| 5 mM | 0.4551 mL | 2.2755 mL | 4.5510 mL | |
| 10 mM | 0.2276 mL | 1.1378 mL | 2.2755 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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