HA15

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

HA15 专门针对 BiP/GRP78/HSPA5。 HA15 对所有测试的黑色素瘤细胞都表现出抗癌活性，包括从患者体内分离的细胞和对 BRAF 抑制剂产生耐药性的细胞。

HA15 targets specifically BiP/GRP78/HSPA5. HA15 exhibits anti-cancerous activity on all melanoma cells tested, including cells isolated from patients and cells that developed resistance to BRAF inhibitors.

HA15 (10 μM; 1-24 hours) induces an early endoplasmic reticulum stress (ER Stress).HA15 (0-10μM; 24 hours) decreases melanoma cell viability in a dose-dependent manner compared with control conditions (DMSO), with an IC50 of 1-2.5 μM in? A375 cells.HA15 (1-10 μM; 24 hours) induces apoptosis in A375 cells.HA15 (1-24 μM; 24 hours) induces autophagy.HA15 (10 μM; 48 hours) has high efficiency in inducing cell death and ER stress in BRAF-inhibitor-resistant melanoma cells. And HA15 inhibits tumor growth through autophagic and apoptotic mechanisms initiated by ER stress.No deleterious effects on the viability of normal human melanocytes or human fibroblasts were observed with low or high doses of HA15. Cell Viability Assay Cell Line:A375 cells Concentration:1 μM,2.5 μM,5 μM,7.5 μM,10 μM Incubation Time:24 hours Result:Decreased melanoma cell viability in a dose-dependent manner compared with control conditions (DMSO) in A375 cells.Apoptosis Analysis Cell Line:A375 cells Concentration:1 μM, 5 μM, 10 μM Incubation Time:24 hours Result:Induces apoptosis.Cell Autophagy Assay Cell Line:A375 cells Concentration:1 μM, 4 μM, 10 μM, 24 μMIncubation Time:24 hours Result:Increased LC3B-II expression after 1 hour and persisted after 24 hours, enhanced the expression level of Beclin 1, clearly be indicated that induces autophagy.Western Blot Analysis Cell Line:A375 cells Concentration:10 μM Incubation Time:1 hour, 4 hours, 10 hours, 24 hours Result:Exhibited a rapid induction within 1 hour of the ER stress markers (phosphorylation of PERK and elF2α and a weak increase in ATF4 and CHOP expression)

HA15 (0.7 mg/mouse/day; i.h.; over 2 weeks) inhibits melanoma tumor development in mice, induces no apparent toxicity and no change in their behavior, body mass, or liver mass, suggesting an absence of hepatomegaly. HA15 (0.7 mg/mouse; i.p.; 5 days/week) suppresses MPM tumor growth in vivo. Animal Model:6-weeks female BALB/c nu/nu (nude) mice with A375 melanoma cells xenograft Dosage:0.7 mg/mouse/day dministration: Subcutaneous injection; over a period of 2 weeks Result:Attenuated the development of tumors.Animal Model:Mouse, NSG (NOD-scid IL2Rγnull) Dosage:0.7 mg/mouse Administration:Intraperitoneal injection, 5 days/week, for 5 weeks Result:Suppressed MPM tumor growth.

HA15 | HA-15 | HA 15

Others

Other Targets

GRP78| HSPA5| BiP

Cancer

——

1609402-14-3

466.58

C23H22N4O3S2

>98% (HPLC)

DMSO : ≥ 50 mg/mL. 107.16 mM; H2O : < 0.1 mg/mL

CC(=O)Nc1nc(c2cccc(NS(=O)(=O)c3c4cccc(N(C)C)c4ccc3)c2)cs1

N-(4-(3-((5-(dimethylamino)naphthalene)-1-sulfonamido)phenyl)thiazol-2-yl)acetamide

(-20℃)

With Ice Pack

≥ 2 years