N-9077 Nintedanib, Free Base, >99%

Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO at 25 mg/mL with warming; very poorly soluble in ethanol; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility. Disposal: A.

VRG-109 VRG-108 VRG-107 VRG-106 VRG-105 VRG-104 VRG-103 VRG-102 VRG-001

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• This product was previously Cat. No. I-9077, Intedanib, and Cat. No. V-9077, Vargatef.
• This research compound is the free base form of nintedanib. We also offer the ethanesulfonate salt form; please see Nintedanib, Ethanesulfonate Salt, Cat. No. N-9055.
• Nintedanib is an indolinone derivative that potently inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and fibroblast growth factor receptor (FGFR) kinase activity in enzymatic assays (table 1). It blocks mitogen-activated protein kinase and Akt signaling pathways in three cell types contributing to angiogenesis, namely endothelial cells, pericytes, and smooth muscle cells, and it inhibits cell proliferation with an EC50 of 10-80 nM. Hilberg, F., et al. "BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy." Cancer Res. 68: 4774-4782 (2008).
• Table 1. In vitro kinase inhibition profile of Nintedanib (adapted from Hilberg, F., et al. 2008). Kinase IC50 (nM)* VEGFR-2 (mouse) 13 ± 4 VEGFR-3 13 ± 10 Lck 16 ± 16 VEGFR-2 21 ± 13 Flt-3 26 VEGFR-1 34 ± 15 FGFR-2 37 ± 2 PDGFRα 59 ± 71 PDGFRβ 65 ± 7 FGFR-1 69 ± 70 FGFR-3 108 ± 41 Src 156 ± 40 Lyn 195 ± 12 FGFR-4 610 ± 117 IGF1R >1,000 InsR >4,000 CDK1 >10,000 CDK2 >10,000 CDK4 >10,000 Other kinases (n = 26) >10,000 EGFR >50,000 HER2 >50,000 * Assays performed with ATP concentrations at the respective Ki. Human kinases were tested except when stated otherwise. Phosphatase PP2A and another 25 kinases were analyzed at 10 µM with 100 µM ATP: GSK3B, ROCKII, DYRK1A, PKCα, MAPK2ERK2, HGFR, MSK1, PDK1, CHK1, MAPKAPK2, SAPK2AP38, S6K1, SGK, CK1, CK2, PKA, SAPK2BP38B2, SAPK3P38G, JNK1A1, SAPK4P38D, PHK, PKBA, CSK, CDK2/CYCLINA, PRAK (data not shown).
• Nintedanib significantly decreased blood vessel area and inhibited tumour growth. Zips, D., et al. "Triple angiokinase inhibition, tumour hypoxia and radiation response of FaDu human squamous cell carcinomas." Radiother. Oncol. 92: 405-410 (2009).
• A reproducible hepatic perfusion index (HPI) was determined by using quantified gadopentetate dimeglumine (Gd-DTPA) concentration. The HPI decreased significantly at 28 days after treatment with nintedanib. HPI may be useful for monitoring antiangiogenic treatment response of hepatic metastases. Miyazaki, K., et al. "Quantitative mapping of hepatic perfusion index using MR imaging: a potential reproducible tool for assessing tumour response to treatment with the antiangiogenic compound BIBF 1120, a potent triple angiokinase inhibitor." Eur. Radiol. 18: 1414-1421 (2008).
• This nintedanib product is the free base form, whose CAS number is given above. The CAS number of the Nintedanib, Ethanesulfonate Salt form is 656247-18-6.
• Another CAS number previously assigned to Nintedanib, Free Base, namely 928326-83-4 has been deleted by CAS and is no longer in use.
• Nintedanib (as the Ethanesulfonate Salt) is the active ingredient in the drug procuct sold under the trade name Vargatef®. This drug has been used in human clinical trials for patients with non-small cell lung, colorectal, uterine, endometrial, ovarian, and cervical cancer and multiple myeloma. NOTE: THE NINTEDANIB, ETHANESULFONATE SALT SOLD BY LC LABORATORIES FOR RESEARCH IS NOT VARGATEF®, AND IS NOT FOR HUMAN USE.
• Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use.
• This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.
• Not available in some countries; not available to some institutions; not available for some uses.