PF-05231023 - FGFR Agonist - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPF-05231023Cat. No.: HY-113697CAS No.: 1037589-69-7分式: CHNO分量: 528.55作靶點(diǎn): FGFR作通路: Protein Tyrosine Kinase/RTK儲(chǔ)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(shí)驗(yàn) DMSO : 125 mg/mL (236.50 mM; Need ultr

2、asonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.8920 mL 9.4598 mL 18.9197 mL5 mM 0.3784 mL 1.8920 mL 3.7839 mL10 mM 0.1892 mL 0.9460 mL 1.8920 mL請(qǐng)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(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn) 請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；

3、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(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (3.94 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (3.94 mM); Clear solution3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (3.94 mM); Cle

4、ar solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 PF-05231023種長(zhǎng)效的成纖維細(xì)胞長(zhǎng)因21 (FGF21) 的類似物，F(xiàn)GF21 受體 的激動(dòng)劑，有治療 2 型糖尿病的潛能 1 5。IC50 & Target FGF21-receptor 5.體外研究 PF-05231023 is a long-acting fibroblast growth factor 21 (FGF21) analog 2.體內(nèi)研究 Administration of native FGF21 a

5、nd PF-05231023 (3mg/kg or 10mg/kg; subcutaneously twice a week fortwo weeks) improves glucose tolerance and liver insulin sensitivity in Zucker rats 3.PF-05231023 (10 mg/kg; intraperitoneally injected) decreases retinal inflammation in diabetic mice. PF-05231023 reduces retinal IL-1 mRNA expression

6、in Akita mice. PF-05231023 increases cone-specificarrestin4 expression in Akita mice. PF-05231023 restores photoreceptor morphology in Akita mice. PF-05231023 inhibits oxidative-stress-induced inflammation in photoreceptors. PF-05231023 decreases thevariability of retinal NRF2 levels and shows a tre

7、nd (non-significant) towards increased NRF2 levels in Akitamice 4.Animal Model: Eight week old Zucker rats 3Dosage: 3mg/kg and 10mg/kgAdministration: Subcutaneously twice a week for two weeksResult: There was no change of BW observed, and food intake was not changed in the treatedgroups compared to

8、control. Caused a significant decrease of glucose excursion duringthe oral glucose tolerance test (OGTT) compared to control.Animal Model: 7-to-8-month-old Akita mice with type 1 diabete model 4Dosage: 10 mg/kgAdministration: Intraperitoneally injected; twice a week; for four weeksResult: Administra

9、tion improved retinal function in diabetic Akita mice.REFERENCES1. Dong JQ, et al. Pharmacokinetics and pharmacodynamics of PF-05231023, a novel long-acting FGF21 mimetic, in a first-in-humanstudy. Br J Clin Pharmacol. 2015 Nov;80(5):1051-63.2. Giragossian C, et al. Mechanistic investigation of the

10、preclinical pharmacokinetics and interspecies scaling of PF-05231023, a fibroblastgrowth factor 21-antibody protein conjugate. Drug Metab Dispos. 2015 Jun;43(6):803-11.3. Bernardo B, et al. FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal model

11、s ofobesity and insulin-resistance. Sci Rep. 2015 Jul 8;5:11382.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE4. Fu Z, et al. Fibroblast Growth Factor 21 Protects Photoreceptor Function in Type 1 Diabetic Mice. Diabetes. 2018 May;67(5):974-985.5. Sonoda J, et al. FGF21-receptor agonists: an emerging therapeutic class for obesity-related diseases. Horm Mol Biol Clin Investig. 2017May 19;30(2).McePdfHeightCaution: Product has