1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEValrubicinCat. No.: HY-13772CAS No.: 56124-62-0Synonyms: AD-32分式: CHFNO分量: 723.64作靶點(diǎn): PKC作通路: Epigenetics; TGF-beta/Smad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 : 130 mg/mL (179.65 mM)

2、H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.17 mg/mL (3.00 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Valrubicin種化療劑，能夠抑制 TPA 和 PDBu 誘導(dǎo)的 PKC 活化，IC50 值分別為 0.85 和 1.25 M，具有抗腫瘤和抗炎作。IC50 & Target TPA-activated PKC PDBu-activated PKC0.85 M (IC50) 1

3、.25 M (IC50)體外研究 Valrubicin (AD 32) is a chemotherapy agent, inhibits TPA- and PDBu-induced PKC activation with IC50s of0.85 and 1.25 M, respectively. Valrubicin inhibits the binding of 3HPDBu to PKC. Therefore, Valrubicincompetes with the tumor promoter for the PKC binding site and prevents the lat

4、ter from both interacting withthe phospholipid and binding to PKC 1. Valrubicin shows cytotoxic activity against squamous cell carcinoma(SCC) cell line colony formation, with IC50s and IC90s of 8.24 1.60 M and 14.81 2.82 M for UMSCC5cells, 15.90 0.90 M, 29.84 0.84 M for UMSCC5/CDDP cells, and 10.50

5、2.39 M, 19.00 3.91 Mfor UMSCC10b cells, respectively. Moreover, Valrubicin in combination with radiation enhances thecytotoxicity 2.體內(nèi)研究 Valrubicin (3, 6, or 9 mg) reduces tumor growth at week 3 by intratumoral jection in hamster. Valrubicin (6mg) combined with minimally cytotoxic irradiation (150,

6、250, or 350 cGy) causes significant tumor shrinkagein hamster 2. Valrubicin (0.1 g/L) significantly reduces the number of infiltrating neutrophils in biopsieschallenged with TPA at 24 h and attenuates chronic inflammation in mice. Valrubicin also decreases theexpression levels of inflammatory cytoki

7、nes in the acute model 3.PROTOCOLCell Assay 2 UMSCC5 cells exposed to Valrubicin (2 M for 3 h), a single dose of radiation (400 cGy), or the combinedtreatment are cultured for a further 12, 24, or 48 hours. At these times, the cells are collected bytrypsinization (0.25%), washed in phosphate-buffere

8、d saline (PBS), and fixed at 5 106 cells/mL with 95%ethanol. Cells are incubated with ribonuclease (50 g; 70-90 Kunitz units/mg for 30 min), and the resultingpellet resuspended in and incubated with propidium iodide (0.05 mg/mL for 10 min). The DNA content of thesamples is determined by flow cytomet

9、ry according to standard technique 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Hamsters 2Administration 2 Hamsters with cheek pouch tumors of 100 mm2 are randomly assigned to one of five treatment groups.Momentarily anesthetized animals eac

10、h receives once a week 3 injections (27 g 0.5-inch needle: 0.1 mLadministered slowly to the base of the lesion) of Valrubicin (3, 6, or 9 mg) or drug vehicle (Cremophor:alcohol;1:1 by volume; NCl diluent 12). A further group of animals receives anesthesia but no direct tumortreatment (control). Indi

11、vidual tumor sizes are measured with calipers at weekly intervals for 4 weeks, atwhich time the animals are sacrificed 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Chuang LF, et al. Acti

12、vation of human leukemia protein kinase C by tumor promoters and its inhibition by N-trifluoroacetyladriamycin-14-valerate (AD 32). Biochem Pharmacol. 1992 Feb 18;43(4):865-72.2. Wani MK, et al. Rationale for intralesional valrubicin in chemoradiation of squamous cell carcinoma of the head and neck.Laryngoscope. 2000 Dec;110(12):2026-32.3. Hauge E, et al. Topical valrubicin application reduces skin inflammation in murine models. Br J Dermatol. 2012 Aug;167(2):288-95.McePdfHeightC