Apoptozole 是一种Hsc70和HSP70的 ATPase 结构域抑制剂，可诱导凋亡，Kd值分别为 0.21 和 0.14?μM。

Apoptozole is an inhibitor of the ATPase domain of Hsc70 and Hsp70, and can induce apoptosis.

Apoptozole induces caspase dependent apoptosis by blocking interaction of HSP70 with APAF-1, without affecting interactions of HSP70 with ASK1, JNK, BAX, and AIF[2]. However, apoptozole may form aggregates under aqueous conditions that could interact with HSP70 proteins in a non-specific manner, potentially leading to false positives and inconsistent data[3].

Apoptozole greatly retards tumor growth in mice xenografted with cancer cells without affecting mouse viability. The elimination half-life time (T1/2) of Az in blood is found to be significantly longer than that of Dox (8.04 versus 1.60 hr) and the time needed to reach a maximum concentration (Tmax) of Az is shorter than that of Dox (1.00 versus 4.00 hr)[2].

Inhibition of HER2/erbB2 tyrosine kinase activity: BT-474 cells are seeded on 24-well plates and cultured overnight. Mubritinib is then added at various concentrations. After incubation for 2 hours, the cells are harvested directly into sodium dodecyl sulfate (SDS)-sample buffer (200 μL). Aliquots containing equal amounts of total cell extract are run on 7.5% to 15% gradient SDS–polyacrylamide gel electrophoresis (PAGE). Following electrophoresis, proteins are transferred onto a polyvinylidene fluoride (PVDF) membrane, for western blot analysis using a relevant primary antibody. Detection of protein is accomplished by an enhanced chemiluminescent (ECL) detection method. The extent of tyrosine phosphorylation of HER2/erbB2 is measured by the LAS-1000 plus lumino-image analyser. The concentration of Mubritinib that inhibits HER2/erbB2 phosphorylation by 50% (IC50) is calculated from a dose–response curve generated by least-squares linear regression of the response using SAS software.

Several cancer cell lines (A549, lung adenocarcinoma epithelial cells; HeLa, cervical cancer cells; MDA-MB-231, breast cancer cells; HepG2, liver cancer cells) are treated with various concentrations (0-15 μM) of Az or compound 7 as a negative control for 18 hr. Cell viabilities are then determined using an MTT assay.(Only for Reference)

1054543-47-3

C33H25F6N3O3

625.571

Apoptosis Activator VII

DMSO:93 mg/mL (148.7 mM)
Ethanol:24 mg/mL (38.4 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years