Lonafarnib-Sch66336-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELonafarnibCat. No.: HY-15136CAS No.: 193275-84-2Synonyms: Sch66336分式: CHBrClNO分量: 638.82作靶點: Farnesyl Transferase; Autophagy作通路: Metabolic Enzyme/Protease; Autophagy儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C

2、1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100 mg/mL (156.54 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.5654 mL 7.8269 mL 15.6539 mL5 mM 0.3131 mL 1.5654 mL 3.1308 mL10 mM 0.1565 mL 0.7827 mL 1.5654 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)

3、的溶解案，配制前請先配制澄清的儲備液，再依次添加助溶劑(為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.91 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (3.91 mM); Clear sol

4、ution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.91 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Lonafarnib種服有效的法尼 蛋轉(zhuǎn)移酶 (FPTase) 抑制劑，作于 H-ras，K-ras 和 N-ras，IC50 分別為 1.9 nM，5.2 nM 和 2.8 nM。IC50 & Target IC50: 1.9 nM (H-ras), 5.2 nM (K-ras)

5、, 2.8 nM (N-ras) 1體外研究 Lonafarnib (Sch66336) potently inhibits Ha-Ras processing in whole cells and blocks the trans formed growthproperties of fibroblasts and human tumor cell lines expressing activated Ki-Ras proteins 1. All treatmentgroups containing Lonafarnib (10 M) show a significantly higher

6、level of unfarnesylated H-Ras (116-137%)compared to control treatment 2.體內(nèi)研究 In mouse, rat, and monkey systems, Lonafarnib (Sch66336) has excellent oral bioavailability andpharmacokinetic properties. In the nude mouse, Lonafarnib demonstrates potent oral activity in a wide arrayof human tumor xenogr

7、aft models including tumors of colon, lung, pancreas, prostate, and urinary bladderorigin 1. Lonafarnib alone (80 mg/kg by oral gavage, once daily) has limited ability to inhibit orthotopic U87tumors compared to vehicle treated control animals (T/C of 0.67). The combination of XRT/Tem (2.5Gy/dayfor

8、2 days; 5 mg/kg by oral gavage 90 min prior to XRT) is designed to produce modest tumor growthinhibition in vivo(T/C of 0.42). Concurrent Lonafarnib/XRT/Tem (Lonafarnib 80 mg/kg by oral gavage, oncedaily, XRT 2.5Gy/day for 2 days, and Tem 5 mg/kg by oral gavage 90 min prior to XRT) provides thestron

9、gest growth reduction (T/C of 0.02) and is significantly more effective than XRT/Tem (p 2.PROTOCOLKinase Assay 1 FPTactivity is determined by measuring the transfer of 3Hfarnesyl from 3Hfarnesyl PPi to trichloroaceticacid-precipitable Ha-Ras-CVLS. GGPT-1 activity is similarly determined using 3Hgera

10、nylgeranyldiphosphate and Ha-Ras-CVLL as substrates 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 CellTiter96 Aqueous Assay kit is used. Assays are performed with 5000 cells/well in a 96-well tissue cultureplate. Plates are irradiated 2

11、4 h after drug exposure and assayed 96 h after XRT, with fresh drug treatmentsapplied each day. For quantification, dye is added directly to each well, plates are washed as per themanufactures recommendation and cell viability determined by optical density. Significance is analyzed usingthe Students

12、 T-test. 12-well plates are seeded with 100,000 cells/well. Drug treatments are initiated 24 hafter plating, and media is replaced every 24 h for a total of 96 h of drug exposure. Plates are irradiated after24 h of drug exposure. Cells from triplicate sets of treatments are trypsonized and counted 4

13、8 h afterirradation using a Z1 series coulter counter, and compared to cell numbers from wells counted on Day 1 (theday drug treatment is initiated). Proliferation after drug treatments are normalized to the control wells andexpressed as % of the control treatment. Significance is analyzed using the

14、 Students T-test 2.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 Lonafarnib is given once daily at 80mg/kg with twice weekly weightings to ensure accurate dosing.Temozolomi

15、de (Tem) is given by gavage at 5 mg/kg 90 min prior to XRT. For irradiation, anesthetized miceare placed in a lead shielding apparatus which limited radiation exposure to the head only. Treatment(2.5Gy/day for two days) is delivered using a Gammacell 40 irradiator delivering 100 rads/min. For in viv

16、ocombination experiments, suboptimal doses of XRT/Tem are selected to permit identification of synergisticeffects of Lonafarnib.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Nat Commun. 2019 May 22;10(1):2265. Aging Cell. 2019 Aug;18(4):e1

17、2979. Sci Rep. 2019 Jul 10;9(1):10021. Med Mycol. 2018 Jun 1;56(4):452-457.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Liu M, et al. Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumorxenograft models and wap-ras transgenic mice. Cancer Res. 1998 Nov 1;58(21):4947-56.2. Chaponis D, et al. Lonafarnib (SCH66336) improves the activity of temozolomide and radiation for o