奧利索西作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetOlesoximeCat. No.: HY-14796CAS No.: 22033-87-0分式: CHNO分量: 399.65作靶點: Mitochondrial Metabolism作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (125.11 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentra

2、tion制備儲備液1 mM 2.5022 mL 12.5109 mL 25.0219 mL5 mM 0.5004 mL 2.5022 mL 5.0044 mL10 mM 0.2502 mL 1.2511 mL 2.5022 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；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液

3、，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.26 mM); Clear solution此案可獲得 2.5 mg/mL (6.26 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO

4、 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.26 mM); Clear solution此案可獲得 2.5 mg/mL (6.26 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄均勻。DMSO 儲備液加到 900 L 20% 的 SBE-CD 理

5、鹽溶液中，混合3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.26 mM); Clear solution此案可獲得 2.5 mg/mL (6.26 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Olesoxime (TRO 19622)種靶向線粒體的神經(jīng)保護(hù)性試劑，促進(jìn)細(xì)胞存活，EC50 為 3.20.2 M。IC & Target M

6、itochondrial1體外研究 Exposure to Olesoxime (TRO 19622) (ranging from 0.1 to 10 M) at 1 h after plating significantly protects primaryembryonic rat spinal MNs (that had been cultured for 3 days without brain-derived, ciliary and glia-derivedneurotrophic factors) from cell death. At a concentration of 10

7、 M, Olesoxime (TRO 19622) maintains survival of7410% of the neurons supported by a combination of neurotrophic factors (brain-derived, ciliary and glia-derivedneurotrophic factors). The mean EC50 in this assay is 3.20.2 M. In addition to preserving MN cell bodies, Olesoxime(TRO 19622) also promotes

8、the outgrowth of neurites. At a concentration of 1 M, which increases cell survival byonly 38%, Olesoxime (TRO 19622) increases overall neurite outgrowth per cell by 54%1. Olesoxime (TRO 19622)belongs to a new family of cholesterol-oximes identified for its survival-promoting activity on purified mo

9、tor neuronsdeprived of neurotrophic factors. Olesoxime (TRO 19622) targets proteins of the outer mitochondrial membrane,concentrates at the mitochondria and prevents permeability transition pore opening mediated by, among otherthings, oxidative stress2.體內(nèi)研究 Daily administration of Olesoxime (TRO 196

10、22) (3 or 30 mg/kg sc) to adult mice for more than 2 months is well tolerated without toxicity or adverse effects1. When animals are treated orally for 5 days following the lesion, Olesoxime (TRO 19622) increases motor neuron cell body survival in a dose-dependent manner with significantrescue at th

11、e highest dose of 100 mg/kg. At this dose, motor neuron survival is 29 2% (n=18) corresponding to a42% increase in survival compared with vehicle-treated animals3. Paclitaxel-treated rats that receive prophylactictreatment with 3 mg/kg/d or 30 mg/kg/d Olesoxime (TRO 19622) have 23917.6 and 24714.4 I

12、ENFs per cm,respectively. For both doses, the decreases are significantly less than the 46% decrease seen in the Paclitaxel-treatedrats administered vehicle. However, both doses produce decreases (25% and 22%) that are significantly differentrelative to the nave control group4.PROTOCOLAnimal Mice3Ad

13、ministration 34 Eight-week-old C57bl/6 RJ mice are anesthetized using 60 mg/kg i.p. ketamine chlorohydrate. To reduce the risk ofgender-related differences in response to Olesoxime (TRO 19622), only female mice are used. The right sciatic nerveis surgically exposed at mid-thigh level, and it is crus

14、hed 5 mm proximal to the trifurcation of the sciatic nerve. Thenerve is crushed twice for 30 s with hemostatic forceps (width, 1.5 mm) with a 90 rotation between each crush.Sciatic nerve degeneration/regeneration is assessed over 6 weeks by measurement of the compound muscular actionpotential (CMAP)

15、 and histological studies of the damaged area of the sciatic nerve. Olesoxime (TRO 19622) is givensubcutaneously at 0.3, 3, and 30 mg/kg. Treatments started the day of the crush injury, and they continued daily for 6weeks. In total, 15 animals per group are used in the study. Electromyography is per

16、formed once a week for 6 weeksusing a Neuromatic 2000M electromyograph. Mice are anesthetized using 100 mg/kg i.p. ketamine chlorohydrate.Page 2 of 3 www.MedChemECMAP is measured in the gastrocnemius muscle after a single 0.2-ms stimulation of the sciatic nerve at supramaximalintensity (12.8 mA). Th

17、e amplitude (millivolts) and the latency (milliseconds) of the action potential are measured.Rats4Adult male Sprague-Dawley rats (200-300 g) are used. Olesoxime (TRO 19622) or the vehicle is administered via oralgavage in a volume of 5 mL/kg. The TRO19622doses used here (3-100 mg/kg) are chosen base

18、d on prior reports ofneuroprotective and analgesic activity.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Martin LJ, et al. Olesoxime, a cholesterol-like neuroprotectant for the potential treatment of amyotrophic lateral sclerosis. IDrugs. 2010 Aug;13(8):568-80.2. Bordet T, et al. Olesoxime (TRO19622): A Novel Mitochondrial-Targeted Neuroprotective Compound. Pharmaceuticals (Basel). 2010 Jan 28;3(2):345-3683. Bordet T, et al. Identification a