Milciclib-PHA-848125-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMilciclibCat. No.: HY-10424CAS No.: 802539-81-7Synonyms: PHA-848125分式: CHNO分量: 460.57作靶點(diǎn): CDK; Autophagy作通路: Cell Cycle/DNA Damage; Autophagy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 :

2、20 mg/mL (43.42 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.1712 mL 10.8561 mL 21.7122 mL5 mM 0.4342 mL 2.1712 mL 4.3424 mL10 mM 0.2171 mL 1.0856 mL 2.1712 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)娜芙獍福渲魄罢?qǐng)先配制澄清的儲(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

3、，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)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(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2 mg/mL (4.34 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2 mg/mL (4.34 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedCh

4、emEBIOLOGICAL ACTIVITY物活性 Milciclib (PHA-848125)種有效的 CDK 和 Tropomyosin receptor kinase (TRK) 雙重 抑制劑，對(duì) cyclinA/CDK2，cyclin H/CDK7，cyclin D1/CDK4，cyclin E/CDK2，cyclin B/CDK1 和 TRKA 的 IC50 值分別為45，150，160，363，398 和 53 nM。IC50 & Target cyclin A/CDK2 cyclin E/CDK2 cyclin H/CDK7 cyclin D1/CDK445 nM (IC50)

5、363 nM (IC50) 150 nM (IC50) 160 nM (IC50)cyclin B/CDK1 TRKA398 nM (IC50) 53 nM (IC50)體外研究 Milciclib (PHA-848125; 0.156 or 0.625 M) up-regulates the expression of PDCD4, DDIT4, SESN2/sestrin 2and DEPDC6/DEPTOR in GL-Mel cells 1. Milciclib (PHA-848125) potently inhibits the kinase activity ofCDK2/cycl

6、in A complex and of TRKA in a biochemical assay, with IC50s of 45 and 53 nM, respectively.Milciclib induces a clear accumulation of cells in G1 phase. Milciclib strongly inhibits NGF-inducedphosphorylation of TRKA in a dose-dependent manner 2.體內(nèi)研究 Milciclib (PHA-848125; 5, 10, and 15 mg/kg, p.o.) in

7、hibits the growth of tumor in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinoma model. Milciclib has significant antitumor activity invarious human xenografts and carcinogen-induced tumors as well as in disseminated primary leukemiamodels, with plasma concentrations in rodents in t

8、he same range as those found active in inhibiting cancercell proliferation 2. Milciclib (PHA-848125; 40 mg/kg) induces a significant tumor growth inhibition in K-RasG12DLA2 mice, and this is accompanied by a reduction in the cell membrane turnover 3.PROTOCOLCell Assay 2 Cells are seeded into 96- or

9、384-well plates at densities ranging from 10,000 to 30,000/cm2 in appropriatemedium plus 10% FCS. After 24 hours, cells are treated in duplicate with serial dilutions of Milciclib, and 72hours later, viable cell number is assessed using the CellTiter-Glo Assay. IC50s are calculated using aSigmoidal

10、fitting algorithm. Experiments are done independently at least twice.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats are randomized and introduced into the study when at least one mammary tumor attained a diameter ofAdministration 2 0.5 cm.

11、Groups of 10 animals are treated orally twice a day continuously for 10 days with vehicle (glucosate)or with 5, 10, and 15 mg/kg of Milciclib, whereas a further group receives two cycles of Milciclib at 20 mg/kgorally twice a day for 5 days with an intervening rest period of 1 week. Tumor volume is

12、measured regularlyby caliper for the duration of the experiment.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) Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Technical University of Munich. 24.01.2018.2/3 Master of Small Molecules 您邊的抑

13、制劑師www.MedChemESee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Caporali S, Alvino E, Levati L, Esposito AI, Ciomei M, Brasca MG, Del Bufalo D, Desideri M, Bonmassar E, Pfeffer U, DAtri S.Down-regulation of the PTTG1 proto-oncogene contributes to the melanoma suppressive effects

14、 of the cyclin-dependent kinase inhibitor PHA-848125.Biochem Pharmacol. 2012 Sep 1;84(5):598-611.2. Albanese C, Alzani R, Amboldi N, Avanzi N, Ballinari D, Brasca MG, Festuccia C, Fiorentini F, Locatelli G, Pastori W, Patton V, RolettoF, Colotta F, Galvani A, Isacchi A, Moll J, Pesenti E, Mercurio C

15、, Ciomei M.Dual targeting of CDK and tropomyosin receptor kinase familiesby the oral inhibitor PHA-848125, an agent with broad-spectrum antitumor efficacy.Mol Cancer Ther. 2010 Aug;9(8):2243-54.3. Degrassi A, et al. Efficacy of PHA-848125, a cyclin-dependent kinase inhibitor, on the K-Ras(G12D)LA2 lung adenocarcinomatransgenic mouse model: evaluation by multimodality imaging.Mol Cance