| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Dovitinib (formerly TKI258 and CHIR258) is a potent, orally bioavailable and multi-targeted RTK (receptor tyrosine kinase) inhibitor with potential anticancer activity. In female BNX mice carrying KMS11 cells, it exhibits strong anti-proliferative activity both in vitro and in vivo, as well as antitumor efficacy. It is less effective against InsR, EGFR, c-Met, EphA2, Tie2, IGFR1, and HER2. It primarily inhibits class III (FLT3/c-Kit) with IC50s of 1 nM/2 nM.It also potently inhibits class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50s of 8–13 nM. Dovitinib attaches itself firmly to FGFR3 and prevents it from being phosphorylated, which may stop tumor cells from proliferating and cause them to die.
| Targets |
FLT3 (IC50 = 1 nM); c-Kit (IC50 = 2 nM); FGFR1 (IC50 = 8 nM); FGFR3 (IC50 = 9 nM); VEGFR3 (IC50 = 8 nM); VEGFR1 (IC50 = 10 nM); VEGFR2 (IC50 = 13 nM); PDGFRβ (IC50 = 27 nM); PDGFRα (IC50 = 210 nM); CSF-1R (IC50 = 36 nM)
|
|
|---|---|---|
| ln Vitro |
|
|
| ln Vivo |
|
|
| Enzyme Assay |
In a time-resolved fluorescence (TRF) or radioactive format, the inhibitory concentration of 50% (IC50) values for the inhibition of RTKs by dovitinib are calculated, measuring the inhibition of phosphate transfer to a substrate by the corresponding enzyme caused by dovitinib. The assay conditions for the kinase domains of FGFR3, FGFR1, PDGFRβ, and VEGFR1-3 are 50 mM HEPES (N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid), pH 7.0, 2 mM MgCl2, 10 mM MnCl2, 1 mM NaF, 1 mM dithiothreitol (DTT), 1 mg/mL of bovine serum albumin (BSA), 0.25 μM biotinylated peptide substrate (GGGGQDGKDYIVLPI), and 1 to 30 μM adenosine triphosphate (ATP), contingent on the Km corresponding to each enzyme. The concentration of ATP is at or slightly below Km. The pH is increased to 7.5 for the c-KIT and FLT3 reactions, and 0.2 to 8 μM ATP is added along with 0.25 to 1 μM biotinylated peptide substrate (GGLFDDPSYVNVQNL). The phosphorylated peptide is captured on streptavidin-coated microtiter plates containing stop reaction buffer (25 mM EDTA [ethylenediaminetetraacetic acid], 50 mM HEPES, pH 7.5) after reactions are incubated at room temperature for one to four hours. The DELFIA TRF system measures phosphorylated peptide using an antiphosphotyrosine antibody (PT66) labeled with europium. Using XL-Fit data analysis software version 4.1 (IDBS), nonlinear regression is used to calculate the concentration of dovitinib for IC50. At ATP concentrations near the ATP Km, the kinase activity of insulin receptor (InsR), PDGFRα, colony-stimulating factor-1 receptor (CSF-1R), and insulin-like growth factor receptor 1 (IGFR1) is inhibited.
|
|
| Cell Assay |
The 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT) dye absorbance is used to measure the viability of cells. In 96-well plates, 5 × 103 (B9 cells) or 2 × 104 (MM cell lines) cells are seeded per well. Increasing concentrations of Dovitinib are incubated with cells along with 30 ng/mL aFGF, 100 μg/mL heparin, or 1% IL-6 where indicated. Ten microliter aliquots of the drug or DMSO diluted in culture medium are added for every Dovitinib concentration. Cells are cultured with 100 nM Dovitinib, 0.5 μM dexamethasone, or both at once when specified for drug combination studies. In order to assess the impact of Dovitinib on the growth of MM cells adherent to BMSCs, 104 KMS11 cells are cultured in the presence or absence of Dovitinib on 96-well plates coated with BMSCs. The incubation period for plates is 48–96 hours. 5 × 103 M-NFS-60 cells/well are cultured with serial dilutions of Dovitinib with 10 ng/mL M-CSF and without granulocyte-macrophage colony-stimulating factor (GM-CSF) in order to evaluate the growth of M-CSF-mediated macrophage colony-growth. Using the Cell Titer-Glo Assay, cell viability is assessed after 72 hours. Every experimental condition is run through three times.
|
|
| Animal Protocol |
8-week-old female BNX mice bearing KMS11 cells
10, 30, or 60 mg/kg Gavage |
|
| References |
| Molecular Formula |
C21H21FN6O
|
|---|---|
| Molecular Weight |
392.43
|
| Exact Mass |
392.18
|
| Elemental Analysis |
C, 64.27; H, 5.39; F, 4.84; N, 21.42; O, 4.08
|
| CAS # |
405169-16-6
|
| Related CAS # |
Dovitinib lactate;692737-80-7;Dovitinib dilactic acid;852433-84-2;Dovitinib-d8;1246819-84-0;Dovitinib lactate hydrate;915769-50-5
|
| Appearance |
Solid powder
|
| SMILES |
CN1CCN(CC1)C2=CC3=C(C=C2)N=C(N3)C4=C(C5=C(C=CC=C5F)NC4=O)N
|
| InChi Key |
PIQCTGMSNWUMAF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H21FN6O/c1-27-7-9-28(10-8-27)12-5-6-14-16(11-12)25-20(24-14)18-19(23)17-13(22)3-2-4-15(17)26-21(18)29/h2-6,11H,7-10H2,1H3,(H,24,25)(H3,23,26,29)
|
| Chemical Name |
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one
|
| Synonyms |
TKI-258; CHIR-258; TKI258; TKI-258; TKI 258; CHIR258; CHIR-258; CHIR 258; Dovitinib lactate
|
| HS Tariff Code |
2934.99.03.00
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.37 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.37 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. 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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/kg |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5482 mL | 12.7411 mL | 25.4823 mL | |
| 5 mM | 0.5096 mL | 2.5482 mL | 5.0965 mL | |
| 10 mM | 0.2548 mL | 1.2741 mL | 2.5482 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05571969 | Recruiting | Drug: 2X-121 and dovitinib | Advanced Solid Tumors | Allarity Therapeutics | February 20, 2023 | Phase 1 |
| NCT01417143 | Completed | Drug: TKI258 (Dovitinib) |
Adenoid Cystic Carcinoma | Seoul National University Hospital |
September 2011 | Phase 2 |
| NCT01714765 | Completed | Drug: Dovitinib Drug: Everolimus |
Metastatic Clear Cell Renal Cancer |
Queen Mary University of London | April 2011 | Phase 1 |
| NCT01921673 | Completed | Drug: Dovitinib and docetaxel | Gastric Cancer | Asan Medical Center | August 2013 | Phase 1 Phase 2 |
| NCT02116803 | Completed | Drug: dovitinib Drug: fulvestrant |
Solid Tumors | Novartis Pharmaceuticals | May 28, 2014 | Phase 2 Phase 3 |
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
