1054543-47-3

Basic information

• Product Name: BenzaMide, 4-[[2-[3,5-bis(trifluoroMethyl)phenyl]-4,5-bis(4-Methoxyphenyl)-1H-iMidazol-1-yl]Methyl]-
• Synonyms: BenzaMide, 4-[[2-[3,5-bis(trifluoroMethyl)phenyl]-4,5-bis(4-Methoxyphenyl)-1H-iMidazol-1-yl]Methyl]-;Apoptosis Activator VII, Apoptozole;Apoptozole;6-BROMO-4-CHLOROQUINOLINE HYDROCHLORIDE (1:1)
• CAS NO: 1054543-47-3
• Molecular Formula: C₃₃H₂₅F₆N₃O₃
• Molecular Weight: 625.5603192
• EINECS: 604-604-1
• Mol File: 1054543-47-3.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 703.5±70.0 °C(Predicted)
• Appearance: /
• Density: 1.33±0.1 g/cm3(Predicted)
• Storage Temp.: +2C to +8C
• Solubility: DMSO (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)
• PKA: 15.98±0.50(Predicted)
• CAS DataBase Reference: BenzaMide, 4-[[2-[3,5-bis(trifluoroMethyl)phenyl]-4,5-bis(4-Methoxyphenyl)-1H-iMidazol-1-yl]Methyl]-(CAS DataBase Reference)
• NIST Chemistry Reference: BenzaMide, 4-[[2-[3,5-bis(trifluoroMethyl)phenyl]-4,5-bis(4-Methoxyphenyl)-1H-iMidazol-1-yl]Methyl]-(1054543-47-3)
• EPA Substance Registry System: BenzaMide, 4-[[2-[3,5-bis(trifluoroMethyl)phenyl]-4,5-bis(4-Methoxyphenyl)-1H-iMidazol-1-yl]Methyl]-(1054543-47-3)

Safety Data

• Hazardous Substances Data: 1054543-47-3(Hazardous Substances Data)

Usage

Uses

Apoptozoleis an inhibitor of heat shock protein 70 (Hsp70) and acts by blocking its ATPase activity. Induces apoptosis in cancer cells.

General Description

A cell-permeable imidazole compound that directly binds anti-apoptotic chaperone Hsc70 and its inducible homologue Hsp70 (Kd = 210 and 140 nM, respectively). Apoptozole is shown to effectively inhibit the proliferation of SK-OV-3, HCT-15, and A549 cancer cell lines (IC50 = 220, 250 and 130 nM, respectively) and induce 90% apoptotic cell death in P19 embryonic carcinoma and A549 lung cancer cultures after 12 h drug treatment (1 μM). Shown to suppress ubiquitination of mutant CFTR and promote membrane trafficking, and restore chloride channel activity.

Biological Activity

apoptozole is an inhibitor of atpase activity of hsp70 [1].the heat shock protein 70 (hsp70) protein family plays diverse roles in biological processes and has multiple functions involved in suppression of apoptotic pathways through multiple anti-apoptotic processes. the two major members, constitutive hsc70 and inducible hsp70, are composed of an n-terminal atpase domain and a c-terminal substrate binding domain [1][2].apoptozole (az) is an inhibitor of atpase activity of hsp70. apoptozole inhibited the atpase activity of hsp70 by binding to its atpase domain. in the presence of 200 μm atp, apoptozole inhibited the atpase activity of hsp70 by 32% and 65% at 100 μm and 200 μm, respectively. apoptozole bound hsp70 but not hsp40, hsp60, and hsp90. in several cancer cell lines, apoptozole induced apoptosis in a dose-dependent way with ic50 values ranged from 5 to 7 μm. in hela cells, apoptozole decreased the amount of apaf-1 associated with hsp70 without affecting the expression level of apaf-1, and produced cleaved procaspase-9, suggesting that apoptozole blocked association of hsp70 with apaf-1 and induced caspase-dependent apoptosis.in the nude mice xenografted with a549, rko (colorectal carcinoma), and hela cells, i.p injection of apoptozole reduced tumor volumes by 61%, 65%, and 68%, respectively [1]. in mice administered with both protein antigen and az, az increased immune responses to administered antigens and produced more antibodies [2].

references

[1]. ko sk, kim j, na dc, et al. a small molecule inhibitor of atpase activity of hsp70 induces apoptosis and has antitumor activities. chem biol. 2015 mar 19;22(3):391-403.[2]. baek kh, zhang h, lee br, et al. a small molecule inhibitor for atpase activity of hsp70 and hsc70 enhances the immune response to protein antigens. sci rep. 2015 dec 3;5:17642.

Upstream product

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Relevant articles and documents

An apoptosis-inducing small molecule that binds to heat shock protein 70

(Chemical Equation Presented) A cell-based screening approach in which annexin V was used as a staining agent identified apoptozole (Az; see scheme) as an imidazole-based molecule which induces apoptosis. Az binds to Hsc70 and Hsp70 (anti-apoptotic chaperone proteins), with dissociation constants of 0.21 and 0.14 μm, respectively, thereby inhibiting their function. Thus, Az possesses antitumor activity and is, therefore, a potential cancer therapeutic agent.

IMIDAZOLE DERIVATIVES THAT INDUCE APOPTOSIS AND THEIR THERAPEUTIC USES

The present invention relates to a pharmaceutical composition comprising compound for induction of apoptosis, a method for inducing cancer cell apoptosis, a method to suppress lymphocyte activation, a method to improve intracellular trafficking of misfolded mutants and a screening method to identify additional compounds useful for inducing apoptosis, and more specifically, it relates to pharmaceutical compositions comprising imidazole derivatives as active gradients for induction of apoptosis to treat various diseases including cancers and immune-related diseases, the method of inducing apoptosis by treating cancer cells with the said pharmaceutical composition, the method of inactivating human lymphocytes by treating lymphocytes with the said pharmaceutical composition, the method of improving intracellular trafficking of misfolded mutants by treating cells containing the mutants with the said pharmaceutical composition, and the screening method for identifying additional compound useful for inducing apoptosis, wherein cells are incubated with the said pharmaceutical composition and detected.