Tanzisertib-CC-930-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETanzisertibCat. No.: HY-15495CAS No.: 899805-25-5Synonyms: CC-930分式: CHFNO分量: 448.44作靶點(diǎn): JNK作通路: MAPK/ERK Pathway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 : 33 mg/mL (73.59 mM)* means s

2、oluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.2300 mL 11.1498 mL 22.2995 mL5 mM 0.4460 mL 2.2300 mL 4.4599 mL10 mM 0.2230 mL 1.1150 mL 2.2300 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(chǔ)備液，并請注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn) CC-930 is dissolved in DMSO at a concentration of 50 mg/mL; a 12.5% s

3、olution is made in PEG4004.BIOLOGICAL ACTIVITY物活性 Tanzisertib (CC-930)是有效的 JNK1/2/3 抑制劑，IC50 分別為61/7/6 nM。IC50 & Target JNK3 JNK2 JNK11/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE6 nM (IC50) 7 nM (IC50) 61 nM (IC50)體外研究 Tanzisertib (CC-930) inhibits the formation of phospho-cJun in human PBMC st

4、imulated by phorbol-12-myristate-13-acetate and phytohemeagglutinin (IC50=1 M) 1. Tanzisertib (CC-930) (1-2 M) substantiallyreduces hepatocyte apoptosis and necrosis, abrogates apoptosis and necrosis in FC-loaded WT hepatocytes2. Tanzisertib (CC-930) blocks the JNK pathway that is activated by pro-f

5、ibrotic cytokines in systemicsclerosis 3.體內(nèi)研究 Tanzisertib (CC-930) (10 and 30 mg/kg, p.o.) inhibits the production of TNFa by 23% and 77% in the acuterat LPS-induced TNFa production PK-PD model 1. Tanzisertib (CC-930) (150 mg/kg) prevents thedevelopment of fibrosis in different models, but can also

6、induce the regression of pre-existing fibrosis 3.PROTOCOLCell Assay 3 Systemic sclerosis (SSc) fibroblasts are incubated with 1 M Tanzisertib (CC-930) in 96-well plates for 20 h.Then MTT is added at a final concentration of 1 mg/mL, and the cells are further incubated at 37C for 4 h.Mock-treated fib

7、roblasts are used as controls, and all other results are normalised to untreated cells.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal To evaluate the regression of fibrosis on inhibition of JNK, a modified model of bleomycin-induced dermalAdmini

8、stration 3 fibrosis is used. In this model, treatment is initiated 3 weeks after the beginning of the challenge withbleomycin, when significant dermal fibrosis is already established. The outcome of six different groups with atotal number of 40 mice is analysed. The first group of mice receive subcu

9、taneous injections of NaCl for 6weeks. The second group is injected for 3 weeks with bleomycin followed by injections of NaCl for another 3weeks to analyse the degree of fibrosis before treatment, and to control the spontaneous regression offibrosis. The third group of mice is killed after 6 weeks o

10、f injections with bleomycin. The fourth and the fifthgroup are treated with Tanzisertib (CC-930) at doses of 50 mg/kg and 150 mg/kg for the last 3 weeks ofcontinuous challenge with bleomycin for 6 weeks. The sixth group is a positive control group consisting ofmice challenged with bleomycin for 6 we

11、eks and treated in parallel with imatinib at doses of 50 mg/kg for thelast 3 weeks.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(xiàn) Science. 2017 Dec 1;358(6367). Nat Cell Biol. 2017 Jun;19(6):698-710. Sci Transl Med. 2018 Jul 18;10(450). pii

12、: eaaq1093. British Pharmacological Society. 2019 Apr. Methods Mol Biol. 2018;1711:351-398.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Plantevin Krenitsky V, et al. Discovery of CC-930, an orally active anti-fibrotic JNK inhi

13、bitor. Bioorg Med Chem Lett. 2012 Feb1;22(3):1433-8.2. Gan LT, et al. Hepatocyte free cholesterol lipotoxicity results from JNK1-mediated mitochondrial injury and is HMGB1 and TLR4-dependent. J Hepatol. 2014 Dec;61(6):1376-84.3. Reich N, et al. Jun N-terminal kinase as a potential molecular target for prevention and treatment of dermal fibrosis. Ann Rheum Dis.2012 May;71(5):737-45.4. Tavernier SJ, et al. Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survival. Nat Cell Biol. 2017Jun;19(6):698