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.
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