法倔唑作用機制 - Medchemexpress - MCE中國

1、Product Data SheetFadrozoleCat. No.: HY-14247ACAS No.: 102676-47-1分式: CHN分量: 223.27作靶點: Aromatase作通路: Others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 : 100 mg/mL (447.89 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液

2、1 mM 4.4789 mL 22.3944 mL 44.7888 mL5 mM 0.8958 mL 4.4789 mL 8.9578 mL10 mM 0.4479 mL 2.2394 mL 4.4789 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，再依次添加助溶劑

3、：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: 2.17 mg/mL (9.72 mM); Clear solution此案可獲得 2.17 mg/mL (9.72 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 21.7 mg/mL 的澄 DMSO 儲備液加到

4、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: 2.17 mg/mL (9.72 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.17 mg/mL (9.72 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 21.7 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合

5、均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.17 mg/mL (9.72 mM); Clear solution此案可獲得 2.17 mg/mL (9.72 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 21.7 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Fadrozole種有效，選擇性和甾體類的 aromatase 抑制劑，IC50 值為6.4 nM。IC & Target IC50: 6.4 nM

6、 (aromatase)1體外研究 Fadrozole hydrochloride is a very potent inhibitor of both human placental and rat ovarian aromatase. In hamsterovarian slices, fadrozole hydrochloride inhibits the production of estrogen with an IC50 of 0.03 M. The production ofprogesterone is inhibited with an IC50 of 120 M. Synt

7、hesis of other cytochrome P-450 dependent steroids can besuppressed to various degrees with higher doses of fadrozole hydrochloride. 1.體內(nèi)研究 Fadrozole hydrochloride is able to inhibit the aromatase-mediated androstenedione-induced uterine hypertrophy inimmature female rats with an ED50 of 0.03 mg/kg

8、when given orally. In the same model, aminoglutethimide elicits the same effect with an ED50 of 30 mg/kg when given orally1. Fadrozole hydrochloride prevents the development ofboth benign and malignant spontaneus mammary neoplasns in female Sprague-Dawley rats. It also slows thespontaneous developme

9、nt of ptuitary pars dta mas in female rats, and reduces the of spontaneous hcu ar tumours inmale and female rats2. Administration of fadrozole in male and female mice suppresses the production of 17b-estradiol, accompanied with a 70% reduction in parasite burden. This protective effect is associated

10、 in male mice witha recovery of the specific cellular immune response. Interleukin-6 (IL-6) serum levels, and its production bysplenocytes, is augmented by 80%, together with a 10-fold increase in its expression in testes of infected male mice.Fadrozole treatment returns these levels to baseline val

11、ues3.PROTOCOLAnimal Rats: Rats are treated with daily dosing with fadrozole hydrochloride (CGS 16949A) in purified water by gavage for 2Administration 23 years. There are 60 rats in each of four groups given 0, 0.05, 0.25 or 1.25 mg/kg daily. Control rats receive only water.Clinical signs are record

12、ed weekly and the animals are examine for palpable masses every 4 weeks for the first 9months, then every 2 weeks for the remainder of the study2.Mice: Fadrozole is administered in the form of sub-dermal long-term release pellets (20 mg/wt kg, in three-week-release pellets), starting 1 week prior to

13、 the infection, using a 10-gauge needle. Three pellets are administratedduring the study. Placebo pellets are administered to another group of infected mice, in the same fashion as theinhibitor. After 1 week, mice are infected and killed 8 weeks later3.MCE has not independently confirmed the accurac

14、y of these methods. They are for reference only.REFERENCESPage 2 of 3 www.MedChemE1. Browne LJ, et al. Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease. JMed Chem. 1991 Feb;34(2):725-36.2. Gunson DE, et al. Prevention of spontaneous tumours in female rats by fadrozole hydrochloride, an aromatase inhibitor. Br J Cancer. 1995 Jul;72(1):72-5.3. Morales-Montor J, et al. Inhibition of p-450 aromatase prevents feminisation and induces protection during cysticercosis. Int J Parasitol. 2002Oct;32(11):1379-