Brivanib Alaninate (BMS-582664) (Synonyms: BMS 582664) |
| رقم الكتالوجGC14238 |
Brivanib alaninate (BMS-582664) هو مثبط تنافسي ضد ATP ضد VEGFR2 مع IC50 من 25 نانومتر ؛ لديه قوة معتدلة ضد VEGFR-1 و FGFR-1 ، ولكن أكثر من 240 ضعفًا ضد PDGFRβ ؛.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 649735-63-7
Sample solution is provided at 25 µL, 10mM.
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BMS-540215 is an ATP-competitive inhibitor of human VEGFR -2, with an IC50 of 25 nmol/L and Ki of 26 nmol/L. In addition, it inhibits VEGFR-1 (IC50 = 380 nmol/L) and VEGFR-3 (IC50 = 10 nmol/L). BMS-540215 also showed good selectivity for FGFR-1 (IC50 = 148 nmol/L), FGFR-2 (IC50 =125 nmol/L), and FGFR-3 (IC50 = 68 nmol/L).
Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) are known to be involved in growth and neovascularization of HCC. Therefore, agents that target these pathways may be effective in the treatment of HCC. Brivanib alaninate is a dual inhibitor ofVEGF receptor (VEGFR) and FGF receptor (FGFR) signaling pathways. Brivanib is hydrolyzed to the active moiety BMS-540215 in vivo.
In vitro: InVEGF-stimulated and basic FGF stimulated SK-HEP1 cells, brivanib significantly inhibited VEGFR-2, FGFR-1, extracellular signal-regulated kinase 1/2, and Akt phosphorylation [1].
In vivo: Six different s.c. patient-derived HCC xenografts were implanted into mice. Tumor growth was evaluated in mice treated with brivanib compared with control. Brivanib significantly suppressed tumor growth in five of six xenograft lines. Tumor weights in these mice that were treated with 50 and 100 mg/kg brivanib by gavage daily for 12 days were approximately 55% and 13%, respectively, compared with vehicle-treated mice. Furthermore, brivanib, at a dose of 100 mg/kg, also inhibited tumor growth in mice with patientderived xenograft lines 2-1318 and 26-1004 [1].
Clinical trial: A total of 750 patients were randomly assigned (376 in arm A and 374 in arm B). Median OS in the intent-to-treat population was 8.8 months in arm A and 8.1 months in arm B. Median progression-free survival (PFS) was 5.0 months in arm A and 3.4 months in arm B. Partial responses observed (13.6% v 7.2%) were higher in arm A. Despite positive effects on PFS and objective response, cetuximab plus brivanib increased toxicity and did not significantly improve OS in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal cancer.
References:
[1] Huynh H, Ngo VC, Fargnoli J, Ayers M, Soo KC, Koong HN, Thng CH, Ong HS, Chung A, Chow P, Pollock P, Byron S, Tran E. Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor tyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma. Clin Cancer Res. 2008;14(19):6146-53.
[2] Siu LL, Shapiro JD, Jonker DJ, Karapetis CS, Zalcberg JR, Simes J, Couture F, Moore MJ, Price TJ, Siddiqui J, Nott LM, Charpentier D, Liauw W, Sawyer MB, Jefford M, Magoski NM, Haydon A, Walters I, Ringash J, Tu D, O'Callaghan CJ. Phase III randomized, placebo-controlled study of cetuximab plus brivanib alaninate versus cetuximab plus placebo in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal carcinoma: the NCIC Clinical Trials Group and AGITG CO.20 Trial. J Clin Oncol. 2013;31(19):2477-84.
Cell experiment: | Viability is measured in LX-2 cells using the Cell Counting Kit-8 (CCK-8). Using 96-well plates with 2,000 cells per well, HSCs are incubated in 10% FBS-supplemented DMEM for 24 hours, followed by starvation in serum-free media. After 24 hours of starvation, brivanib is added at different doses. Two hours later, 5 ng/mL PDGF-BB is added. The cells are incubated for an additional 72 hours and cell viability is measured. Each experiment is performed in three replicates at least four times[3]. |
Animal experiment: | Male mice 4-6 weeks of age are treated 3 times a week with a total of 12 intraperitoneal (i.p.) injections of 150 mL/kg TAA. At the onset of TAA treatment, placebo or brivanib (25 or 50 mg/kg) is administered orally on 5 consecutive days with weekend breaks. The animals are sacrificed 4 weeks after the start of the injections[3]. |
References: [1]. Bhide RS, et al. Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor. J Med Chem, 2006, 49 (7), 2143-2146. | |
| Cas No. | 649735-63-7 | SDF | |
| المرادفات | BMS 582664 | ||
| Chemical Name | [(2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-yl] (2S)-2-aminopropanoate | ||
| Canonical SMILES | CC1=CC2=C(N1)C=CC(=C2F)OC3=NC=NN4C3=C(C(=C4)OCC(C)OC(=O)C(C)N)C | ||
| Formula | C22H24FN5O4 | M.Wt | 441.46 |
| الذوبان | ≥ 22.05mg/mL in DMSO | 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2652 mL | 11.3261 mL | 22.6521 mL |
| 5 mM | 0.453 mL | 2.2652 mL | 4.5304 mL |
| 10 mM | 0.2265 mL | 1.1326 mL | 2.2652 mL |
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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.
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Quality Control & SDS
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- Purity: >99.00%
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Average Rating: 5 (Based on Reviews and 37 reference(s) in Google Scholar.)
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