CC-401-hydrochloride-CC401-HCl-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECC-401 hydrochlorideCat. No.: HY-13022CAS No.: 1438391-30-0Synonyms: CC401 HCl分式: CHClNO分量: 424.93作靶點: JNK作通路: MAPK/ERK Pathway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 (235

2、.33 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.3533 mL 11.7666 mL 23.5333 mL5 mM 0.4707 mL 2.3533 mL 4.7067 mL10 mM 0.2353 mL 1.1767 mL 2.3533 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，并請注意儲備液的保存式和期限。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?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄

3、清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；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. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.88 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.88 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/4 Master of Small

4、Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (5.88 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 CC-401 hydrochloride種有效的 JNK 抑制劑，Ki 為 25 到 50 nM。IC50 & Target JNK25-50 nM (Ki)體外研究 CC-401 has at least 40-fold selectivity for JNK compared with other related kinases, including p38,extracellular sign

5、al-regulated kinase (ERK), inhibitor of B kinase (IKK2), protein kinase C, Lck, zeta-associated protein of 70 kDa (ZAP70). In cell-based assays, 1 to 5 M CC-401 provides specific JNKinhibition. CC-401, a small molecule that is a specific inhibitor of all three JNK isoforms. CC-401competitively binds

6、 the ATP binding site in JNK, resulting in inhibition of the phosphorylation of the N-terminalactivation domain of the transcription factor c-Jun. The specificity of this inhibitor is tested in vitro usingosmotic stress of the HK-2 human tubular epithelial cell line. CC-401 inhibits sorbitol-induced

7、 phosphorylationof c-Jun in a dosage-dependent manner. However, CC-401 does not prevent sorbitol-inducedphosphorylation of JNK, p38, or ERK 1.體內(nèi)研究 The staining of p-JNK is moderately induced in bevazicumab and Oxaliplatin treatments as compared tocontrol, and in the CC-401-treated samples p-cJun con

8、tent is significantly lower, consistent with effectiveJNK inhibition. DNA damage is modestly elevated in combined treatments with CC-401 2. CC-401treatment from days 7 to 24 slows the progression of proteinuria, which is significantly reduced compared tothe no-treatment and vehicle groups at days 14

9、 and 21. However, there is still an increase in the degree ofproteinuria at day 21 in CC-401-treated rats compared to proteinuria at day 5. The vehicle and no-treatmentgroups developed renal impairment at day 24 as shown by an increase in serum creatinine. This is preventedby CC-401 treatment 3.PROT

10、OCOLCell Assay 1 Human HK-2 proximal tubular epithelial cells are cultured in DMEM/F12 media supplemented with 10% FCS,10 ng/mL EGF, and 10 g/mL bovine pituitary extract. For Western blot studies, cells are seeded into six-wellplates and allowed to adhere overnight, and medium is changed to DMEM/F12

11、 supplemented with only 0.5%FCS for 24 h, by which time cells are confluent. CC-401 is prepared in citric acid (pH 5.5) and added to theconfluent cells 1 h before the addition of 300 mM sorbitol, and cells are harvested 30 min later using urea-RIPA buffer. Three experiments are performed, each with

12、two replicates per condition. For ELISAexperiments, HK-2 cells are seeded into 24-well plates, allowed to adhere overnight, cultured in DMEM/F12with 0.5% FCS for 24 h, and then incubated with CC-401 or vehicle for 60 min before stimulation with 1 MAngiotensin II (AngII). Supernatants are harvested 4

13、8 h later and assayed for TGF-1 content using acommercial ELISA kit. Three experiments are performed, each using six replicates per condition 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/4 Master of Small Molecules 您邊的抑制劑師www.MedChemEAnimal Mice

14、2Administration 23 To assess the efficacy of JNK signaling inhibition by CC-401 in anti-angiogenic and Oxaliplatin combinationtherapy in a mouse xenograft model, adult (8-10 weeks of age) female severe combined immunodeficientmice (C.B.17 SCID) are used. To generate tumors, HT29 cells (1106 cells) a

15、re injected subcutaneously intothe left flank of the mice. When the tumors reached approximately 200 mm3, mice are divided into eightgroups (eight mice per group) for treatment with Bevacizumab, Oxaliplatin, CC401, and the appropriatecombinations of Bevacizumab, Oxaliplatin and CC-401. Mice in the B

16、evacizumab treatment group receive 5mg/kg of Bevacizumab by intraperitoneal injection every 3 days for 21 days. The Oxaliplatin treatment groupis injected intraperitoneally with 5 mg/kg Oxaliplatin per week for 2 weeks. The CC-401 treatment group isinjected intraperitoneally 25 mg/kg for every 3 day

17、s. The combination treatment groups receive Bevacizumab(every 3 days, 5 mg/kg), Oxaliplatin (weekly for 2 weeks, 5 mg/kg), and CC-401 (every 3 days, 25 mg/kg).The control group receive saline intraperitoneally. Tumor volume and body weight are measured every 3days. Tumor volume is calculated. Tumor

18、growth delay is calculated as the difference in the time for controland treated tumors to grow from 200 to 800 mm3. For tumor growth delay calculations, mice are continued toreceive treatments till the tumor volume reached 800 mm3. For immunohistochemistry mice are sacrificedafter treatments on day

19、9 for tumor processing and staining.Rats 3Female WKY rats (180-220 g) are used. Groups of 9 or 10 rats are immunized by subcutaneous injection of 5mg of sheep IgG in Freunds complete adjuvant followed 5 days later (termed day 0) by a tail vein injection ofsheep anti-rat GBM serum. In this study, CC-

20、401 (200 mg/kg/b.i.d. by oral gavage) or vehicle (sodium citrate)treatment is initiated in groups of 9 or 10 rats at 7 days after anti-GBM serum administration and continuedtwice daily thereafter until animals are killed at day 24. Additional groups of rats without treatment are killedat day 7 or da

21、y 24 after anti-GBM serum injection as controls. Animals are housed in metabolic cages for 22hours to collect urine on days 5, 14, and 21. Blood is collected at the time of death. Analysis of serumcreatinine and urinary protein are performed.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 Science. 2017 Dec 1;358(6367). Cell Syst. 2018 Apr 25;6(4):424-443.e7. Mol Cancer Res. 2016 Aug;14(8):753-63. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Ma FY, et al. A pathoge