1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEHA15Cat. No.: HY-100437CAS No.: 1609402-14-3分式: CHNOS分量: 466.58作靶點: HSP; Autophagy作通路: Cell Cycle/DNA Damage; Metabolic Enzyme/Protease;Autophagy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 DMS

2、O : 50 mg/mL (107.16 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.36 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 HA15種效特異性的內(nèi)質(zhì)伴侶蛋 BiP/GRP78/HSPA5 抑制劑，可抑制 BiP 的 ATP 酶活性，具有抗腫瘤活性 1。IC50 & Target BiP/GRP78/HSPA5 1體外研究HA15 (10 M; 1-24 ho

3、urs) induces an early endoplasmic reticulum stress (ER Stress) 1.HA15 (0-10M; 24 hours) decreases melanoma cell viability in a dose-dependent manner compared withcontrol conditions (DMSO), with an IC50 of 1-2.5 M in A375 cells 1.HA15 (1-10 M; 24 hours) induces apoptosis in A375 cells 1.HA15 (1-24 M;

4、 24 hours) induces autophagy 1.HA15 (10 M; 48 hours) has high efficiency in inducing cell death and ER stress in BRAF-inhibitor-resistantmelanoma cells. And HA15 inhibits tumor growth through autophagic and apoptotic mechanisms initiated byER stress 1.No deleterious effects on the viability of norma

5、l human melanocytes or human fibroblasts were observed withlow or high doses of HA15 1.Cell Viability Assay 1Cell Line: A375 cellsConcentration: 1 M,2.5 M,5 M,7.5 M,10 MIncubation Time: 24 hoursResult: Decreased melanoma cell viability in a dose-dependent manner compared with controlconditions (DMSO

6、) in A375 cells.Apoptosis Analysis 1Cell Line: A375 cellsConcentration: 1 M, 5 M, 10 MIncubation Time: 24 hoursResult: Induces apoptosis.Cell Autophagy Assay 1Cell Line: A375 cellsConcentration: 1 M, 4 M, 10 M, 24 MIncubation Time: 24 hoursResult: Increased LC3B-II expression after 1 hour and persis

7、ted after 24 hours, enhanced theexpression level of Beclin 1, clearly be indicated that induces autophagy.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEWestern Blot Analysis 1Cell Line: A375 cellsConcentration: 10 MIncubation Time: 1 hour, 4 hours, 10 hours, 24 hoursResult: Exhibited a rapid indu

8、ction within 1 hour of the ER stress markers (phosphorylation ofPERK and elF2 and a weak increase in ATF4 and CHOP expression)體內(nèi)研究 HA15 (0.7 mg/mouse/day; i.h.; over 2 weeks) inhibits melanoma tumor development in mice, induces noapparent toxicity and no change in their behavior, body mass, or liver

9、 mass, suggesting an absence ofhepatomegaly 1.Animal Model: 6-weeks female BALB/c nu/nu (nude) mice with A375 melanoma cells xenograft 1Dosage: 0.7 mg/mouse/dayAdministration: Subcutaneous injection; over a period of 2 weeksResult: Attenuated the development of tumors.REFERENCES1. Cerezo M et al. Co

10、mpounds Triggering ER Stress Exert Anti-Melanoma Effects and Overcome BRAF Inhibitor Resistance. Cancer Cell.2016 Jun 13;29(6):805-19.2. Ruggiero C, et al. The GRP78/BiP inhibitor HA15 synergizes with mitotane action against adrenocortical carcinoma cells throughconvergent activation of ER stress pathways. Mol Cell Endocrinol. 2018 Oct 15;474:57-64.McePdfHeightCaution: Product has not been fully v