PMX-205-Trifluoroacetate - Complement System Antagonist - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPMX 205 TrifluoroacetateCat. No.: HY-110136A分式: CHFNO分量: 953.06作靶點: Complement System作通路: Immunology/Inflammation儲存式: Powder -20C 3 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 H2O : 0.67 mg/mL (0.70 mM; Need ultrasonic)請根

2、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。BIOLOGICAL ACTIVITY物活性 PMX 205 Trifluoroacetate種有效的補體 C5a 受體 (C5aR; CD88) 拮抗劑。IC50 & Target C5aR 1體外研究 A complement activation product, C5a, is known to recruit and activate microglia and astrocytes in vitro byactivation of a G protein-coupled cell-surface C

3、5aR. In the MTT assay, in 24 h plate, it shows that all groupsare significant when compared with negative control group. For PMX 205 (PMX205) group, the valuerecorded is in between 0.09893 to 0.2465, EP54 group, 0.02724 to 0.1748 and Tamoxifen group, the valuerecorded in between 0.09880 to 0.2464. F

4、or the 48 h plate of incubation time, only two groups show asignificant result, which are PMX 205 and Tamoxifen. The values recorded are in between 0.04987 to 0.3273and 0.5777 to 0.8551 respectively. For the 72 h plate, only one group shows a significant result, PMX 205(antagonist group) with the va

5、lue recorded in between 0.02136 to 0.5322 1.體內(nèi)研究PMX 205 (PMX205) is an orally active, selective C5aR antagonist. Animals treated with PMX 205 (1mg/kg/day, oral) display a significant extension of survival time and a reduction in end-stage motor scores, ascompared with vehicle-treated rats. PMX 205-t

6、reated animals also display reduced levels of astroglialproliferation in the lumbar spinal cord. SOD1G93A rats are orally dosed with PMX 205 (1 mg/kg/day) fromtwo time points (days 28 and 70) before the onset of major clinical symptoms. Both treatment groups have a1/2 Master of Small Molecules 您邊的抑制

7、劑師www.MedChemEsignificant extension in survival time compared with untreated rats (p=0.022, day 28; p=0.015, day 70), withno clear differences in outcomes between the two treatment regimens 2. Tg2576 mice are treated with PMX205 (PMX205) at 20 g/mL in the drinking water (n=17) from 12 to 15 mo of ag

8、e, the time frame at whichthere is a rapid accumulation of amyloid deposits in these animals. Untreated Tg2576 animals (n=11) areused as controls. After 3 mo, animals treated with PMX 205 show significantly less fibrillar plaque load(thioflavine reactivity) than do untreated animals. In 3Tg mice, PM

9、X 205 also significantly reduceshyperphosphorylated tau (69%) 3.PROTOCOLCell Assay 1 The mouse mammary tumor cell lines 4T1 are plated at a density 5.0104 cells/ml/well of 96-multiwell platesin complete medium. After 24 h of incubation, the medium is changed with serum starve medium tosynchronize th

10、e cell cycle and growth as to ensure that the cells reaches its plateau phase. After 24 h ofserum-starving, cells are treated with 5 L/well of 0.1 M of agonist, EP54, antagonist, PMX 205 and thepositive control is treated with Tamoxifen drug. 5 L/well of the 12 mM ck solution is added 5 h beforeread

11、ing is taken and about 50 L/well of the SDS-HCL solution is added and mixed thoroughly using pipette3 h before reading is taken. The MTT assay is assessed at different time point; 0, 24, 48 and 72 h atwavelength 570 nm respectively by using ELISA plate reader Infinite M200 1.MCE has not independentl

12、y confirmed the accuracy of these methods. They are for reference only.Animal Rats 2Administration 23 Transgenic SOD1G93A rats expressing human mutant G93A SOD1 (NTac:SD-Tg SOD1G93A L26H) areused. Three experimental groups are chosen: untreated, PMX 205 treats from day 28 onward, and PMX 205treats f

13、rom day 70 onward. Animals are administered PMX 205 via drinking water (1 mg/kg/day) , from day28 or day 70 onward; controls receive water only 2.Mice 3Tg2576 mice are treated (starting at or after the initiation of plaque pathology) for 2-3 mo with PMX 205 givenin the drinking water only (10-20 g/m

14、L, equivalent to 3-6 mg/kg/day) or both in drinking water (10-20 g/mL) and s.c. (1 mg/kg) twice weekly throughout the treatment period. Untreated transgenic animals ofsame age are used as controls. Nontransgenic littermates are similarly treated or not treated with the drug.3Tg mice are also treated

15、 with PMX 205 in the drinking water. Due to the low pathology of the males, onlyfemale mice of this strain are used for these studies 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Kosni NN, et al. Expression of complement C5a receptor a

16、nd the viability of 4T1 tumor cells following agonist-antagonist treatment. JCancer Res Ther. 2016 Apr-Jun;12(2):590-6.2. Woodruff TM, et al. The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis. J Immunol. 2008Dec 15;181(12):8727-34.3. Fonseca MI, et al. Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models ofAlzheimers disease. J Immunol. 2009 Jul 15;183(2):1375-83.