Nintedanib esylate (Synonyms: Nintedanib) |
Catalog No.GC36745
One-Click Copy Product Info
|
Nintedanib esylate, as a kinase inhibitor, used for the treatment of non-small cell lung cancer suffered from first-pass metabolism which resulted in low oral bioavailability (~ 4.7%).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 656247-18-6
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Nintedanib esylate, as a kinase inhibitor, used for the treatment of non-small cell lung cancer suffered from first-pass metabolism which resulted in low oral bioavailability (~ 4.7%)[1]. Nintedanib is an effective inhibitor of multityrosine kinase receptors.
In vitro, treatment with 1-4 µM nintedanib in a dose-dependently manner in Keloid fibroblasts inhibited cell proliferation, induced G0/G1 cell cycle arrest, and suppressed migration and invasion of keloid fibroblasts[2]. In vitro test it shown that at 1 µM Nintedanib and 2.5 mM Pirfenidone decreased fibrotic gene expression including Collagen 1a1 and Fibronectin in murine and human 3D-LTCs as well as pmATII cells[3]. In vitro, 0.01-1.0 µM nintedanib in IPF (Idiopathic pulmonary fibrosis) fibroblasts decreased the expression of collagen I and V, fibronectin, and FKBP10 and attenuated the secretion of collagen I and III[4].
In vivo efficacy test it exhibited that treatment with 5 mg/mL nintedanib in eye drops four times daily, the outgrowths of blood and lymphatic vessels were obviously inhibited compared with the controls[5]. In vivo, treatment with 3 µM and 5 µM nintedanib in mice up-regulated SP-D (Pulmonary surfactant protein D) messenger RNA expression[6]. In vivo experiment it demonstrated that treatment with nintedanib (50, 100 mg/kg) orally could obviously recover the experimental colitis-related symptoms of mice caused by DSS, such as weight loss, increased DAI, shortened colon length, and colonic tissue injury[7].
Kala SG, et al. Bioavailability enhancement of vitamin E TPGS liposomes of nintedanib esylate: formulation optimization, cytotoxicity and pharmacokinetic studies. Drug Deliv Transl Res. 2022 Nov;12(11):2856-2864.
Zhou BY, et al. Nintedanib inhibits keloid fibroblast functions by blocking the phosphorylation of multiple kinases and enhancing receptor internalization. Acta Pharmacol Sin. 2020 Sep;41(9):1234-1245.
Lehmann M, et al. Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis. Respir Res. 2018 Sep 15;19(1):175.
KnÜppel L, et al. A Novel Antifibrotic Mechanism of Nintedanib and Pirfenidone. Inhibition of Collagen Fibril Assembly. Am J Respir Cell Mol Biol. 2017 Jul;57(1):77-90.
Lin T, et al. Inhibition of lymphangiogenesis in vitro and in vivo by the multikinase inhibitor nintedanib. Drug Des Devel Ther. 2017 Apr 5;11:1147-1158.
Kamio K, et al. Nintedanib modulates surfactant protein-D expression in A549 human lung epithelial cells via the c-Jun N-terminal kinase-activator protein-1 pathway. Pulm Pharmacol Ther. 2015 Jun;32:29-36.
Li H, et al. Nintedanib Alleviates Experimental Colitis by Inhibiting CEBPB/PCK1 and CEBPB/EFNA1 Pathways. Front Pharmacol. 2022 Jul 14;13:904420.
References:
| Cell experiment [1]: | |
|
Cell lines |
HUVECs |
|
Preparation Method |
The cell viability was detected after HUVECs were added with Nintedanib (1, 5, 10, 25, 50, and 100 µM) to determine the optimized incubation concentrations. |
|
Reaction Conditions |
1, 5, 10, 25, 50, and 100 µM; for 24 hours |
|
Applications |
When the concentration of Nintedanib was greater than 50 µM, a significantly declined viability of HUVECs was observed. |
| Animal experiment [2]: | |
|
Animal models |
male TRAMP mice |
|
Preparation Method |
In pre-clinical efficacy evaluation, male TRAMP mice starting at 8 and 12 weeks of age were orally-fed with vehicle control (10% Tween 20) or Nintedanib (10 mg/Kg/day in vehicle control) for 4 weeks, and sacrificed immediately after 4 weeks of drug treatment or sacrificed 6-10 weeks after stopping drug treatments. |
|
Dosage form |
10 mg/Kg/day; p.o. |
|
Applications |
In pre-clinical TRAMP studies, Nintedanib led to a delay in tumor progression in all treatment groups; the effect was more pronounced when treatment was given at the beginning of the glandular lesion development and continued till study end. |
|
References: Li L, et al. Nintedanib ameliorates oxidized low-density lipoprotein -induced inflammation and cellular senescence in vascular endothelial cells. Bioengineered. 2022 Mar;13(3):6196-6207. | |
| Cas No. | 656247-18-6 | SDF | |
| Synonyms | Nintedanib | ||
| Canonical SMILES | O=C(C1=CC(NC/2=O)=C(C=C1)C2=C(NC3=CC=C(N(C)C(CN4CCN(C)CC4)=O)C=C3)/C5=CC=CC=C5)OC.CCS(=O)(O)=O | ||
| Formula | C33H39N5O7S | M.Wt | 649.76 |
| Solubility | DMSO: 92.85 mg/mL (142.90 mM and warming) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.539 mL | 7.6951 mL | 15.3903 mL |
| 5 mM | 307.8 μL | 1.539 mL | 3.0781 mL |
| 10 mM | 153.9 μL | 769.5 μL | 1.539 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 20 reference(s) in Google Scholar.)