| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
IC50s for JAK2: 0.9 nM; TrkA:25 nM; FLT3: 3 nM
Target: Lesraurtinib targets multiple tyrosine kinases including JAK2, FLT3, and TrkA with IC50 values of 0.9 nM, 3 nM, and <25 nM respectively. It also inhibits Aurora kinase A and B with IC50 values of 8.1 and 2.3 nM respectively, and prevents STAT5 phosphorylation with IC50 of 20-30 nM. The compound inhibits RPTKs (receptor protein tyrosine kinases) phosphorylation. By inhibiting these kinases, it suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. |
|---|---|
| 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].
In Vitro Activity: Lesraurtinib inhibits proliferation of anaplastic thyroid cancer (ATC) cells with IC50 values of 0.21 μM for KMH2, 0.41 μM for CAL62, and 2.35 μM for THJ-21T cells. It totally inhibits pSTAT5 expression at 4 μM and decreases STAT5 phosphorylation in a concentration-dependent manner. On WI-38, CAL62, and KMH2 cells, lestaurtinib (0.5 μM; 24 hours) exhibits anti-proliferative effects. In CAL62 and KMH2 cells, it causes cell cycle arrest in the G2/M phase at 4 μM. Lestaurtinib (30-300 nM; 48 hours) induces apoptosis in Hodgkin lymphoma cell lines in a dose-dependent manner. At 300 nM, it suppresses phosphorylation of JAK2, STAT5, and STAT3. |
| 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].
In Vivo Activity: Lestaurtinib (20 mg/kg; subcutaneous injection; once daily on weekends and twice on weekdays) significantly inhibits tumor growth in vivo. In medulloblastoma models arising in SmoA1 transgenic mice, lestaurtinib (CEP-701) inhibits Citron kinase (CITK) with IC50 of 90 nM and demonstrates biological effects. The compound has been studied in various xenograft models for its antitumor activity. It is orally bioavailable, enabling convenient oral administration in preclinical and clinical studies. |
| Enzyme Assay |
In Vitro Enzyme/Receptor Binding Protocol: Kinase assays typically use recombinant kinase domains and radiolabeled ATP to measure inhibition of phosphorylation. IC50 values are determined by measuring residual kinase activity after incubation with varying concentrations of lestaurtinib. FLT3 autophosphorylation inhibition is assessed using immunoprecipitation and Western blotting. For JAK2/STAT5 signaling studies, cells are treated with compound and phosphorylation of STAT5 is measured by Western blot or phospho-specific ELISA.
|
| 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 In Vitro Cell-Based Assay Protocol: Cell viability assays: KMH2, CAL62, and THJ-21T cells are treated with 0.01-10 µM lestaurtinib for 72 hours. Cell proliferation assays: WI-38, CAL62, and KMH2 cells are treated with 0.5 µM for 24 hours. Cell cycle analysis: CAL62 and KMH2 cells are treated with 4 μM lestaurtinib. Apoptosis assays: Hodgkin lymphoma cell lines are treated with 30-300 nM for 48 hours. Phosphorylation studies: cells are treated with 30, 100, and 300 nM for 1 hour. |
| 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. In Vivo Animal Assay Protocol: Mouse xenograft models are used for in vivo efficacy studies. Lestaurtinib is administered via subcutaneous injection at 20 mg/kg. Dosing schedule: once daily on Saturday and Sunday, twice daily Monday through Friday. In medulloblastoma models, the drug is injected into tumors arising in SmoA1 transgenic mice. Tumor growth inhibition is monitored and compared to control groups. Body weight and general health are monitored for toxicity. |
| ADME/Pharmacokinetics |
Pharmacokinetics: Lestaurtinib is orally bioavailable. As an indolocarbazole derivative, it has favorable pharmacokinetic properties for oral administration. Detailed PK parameters including half-life, Cmax, and bioavailability have been characterized in preclinical and clinical studies. The compound's oral bioavailability supports its evaluation in clinical trials for leukemia and other cancers. Protein binding and tissue distribution have been studied in the context of its clinical development.
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| Toxicity/Toxicokinetics |
Toxicity: Lestaurtinib has been evaluated in clinical trials for leukemia, myeloproliferative disorders, and other cancers with an established safety profile. No significant toxicity concerns have been reported at therapeutic doses. Comprehensive toxicity data are available from clinical studies. Common adverse effects are typical of kinase inhibitors and may include gastrointestinal disturbances, fatigue, and hematological effects. The compound is for research and clinical investigation use.
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| References |
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| Additional Infomation |
LSM-1231 is an indolecarbazole compound. Lestaurtinib is an orally bioavailable indolecarbazole derivative with antitumor activity. Lestaurtinib inhibits the autophosphorylation of FMS-like tyrosine kinase 3 (FLT3), thereby inhibiting FLT3 activity and inducing apoptosis in FLT3-overexpressing tumor cells. (NCI05)
Drug Indications It has been studied for the treatment of pancreatic cancer, prostate cancer, and myeloid leukemia. Mechanism of Action Lestaurtinib inhibits the autophosphorylation of FMS-like tyrosine kinase 3 (FLT3), thereby inhibiting FLT3 activity and inducing apoptosis in FLT3-overexpressing tumor cells. Additional Information: Lesraurtinib has CAS number 111358-88-4. It is also known as CEP-701, KT-5555, SP-924, and lestaurtinib. The compound is an indolocarbazole derivative with antineoplastic properties. It has been investigated for the treatment of leukemia and myeloproliferative disorders. Lestaurtinib promotes c-MYC expression and inhibits RPTK phosphorylation. It induces apoptosis and cell growth arrest. The compound has high affinity for TrkA and JAK2. For research and clinical investigation use only. |
| Molecular Formula |
C26H21N3O4
|
|---|---|
| Molecular Weight |
439.46
|
| Exact Mass |
439.153
|
| CAS # |
111358-88-4
|
| PubChem CID |
126565
|
| Appearance |
White to off-white solid powder
|
| Density |
1.7±0.1 g/cm3
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| Boiling Point |
723.0±60.0 °C at 760 mmHg
|
| Melting Point |
215-220ºC
|
| Flash Point |
391.0±32.9 °C
|
| Vapour Pressure |
0.0±2.5 mmHg at 25°C
|
| Index of Refraction |
1.880
|
| LogP |
3.37
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
33
|
| Complexity |
886
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
C[C@@]12[C@](C[C@@H](O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)CNC6=O)(CO)O
|
| 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
|
| 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
|
| 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
|
| 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)
|
| 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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