Prodrug-Alcohol

Creative Biolabs has long been a forward-looking service provider in the field of antibody-directed enzyme prodrug therapy (ADEPT) development. We have served numerous worldwide clients with satisfactory products and services. Now, we are happy to introduce our perfect alcohol as a prodrug for antibody-alcohol dehydrogenase conjugate-based ADEPT development. We believe our high-quality products and services will accelerate your research progress.

Alcohol

In chemistry, alcohol always refers to any organic compound in which the hydroxyl functional group (-OH) is bound to a carbon. It is used as a drug and the main alcohol material added in alcoholic beverages. Methanol and ethanol are the simplest and the most important members of alcohols class including all compounds the general formula for which is CnH2n+1OH. Ethanol can denature proteins, but pure ethanol cannot penetrate into the inner layer of the bacterial cell wall. So the sterilization effect of pure ethanol is weak. High purity ethanol (~95%) can dehydrate bacterial cells, but cannot kill bacteria cells completely. Thus, 75% of ethanol is used for medical disinfection.

Ethanol consists of two carbons, six hydrogens, and one oxygen. Fig.1 Ethanol consists of two carbons, six hydrogens, and one oxygen.

MOA of Alcohol

Alcohol as a prodrug is catalytic hydrolysis by exclusively enzyme alcohol dehydrogenase, producing parent drug acetaldehyde. Acetaldehyde (ACH) produced in the physiological metabolism of ethanol can be potentially toxic and immunomodulating. The antitumor activity of an ADEPT system which uses antibody delivered alcohol dehydrogenase (ADH) to convert ethanol to acetaldehyde inside cancer cells has been investigated in vitro and in vivo. In vitro experiments confirmed the toxicity of acetaldehyde to a number of tumour cell lines. While not previously described as a therapeutic agent, the ability of acetaldehyde exposure to damage or inhibit cell growth has been well characterized. Prolonged exposure to high acetaldehyde concentrations could lead to cell death or promote synergistic cytotoxicity in targeted cells when combined with conventional chemotherapy agents.

The mechanism of acetaldehyde kills tumor cells. Fig.2 The mechanism of acetaldehyde kills tumor cells. (Garaycoechea, 2013)

Alcohol-based ADEPT

ADEPT is a promising therapeutic schedule for selectively targeting cancer cells. Ethanol can produce acetaldehyde (AcH) in the physiological metabolism that is potentially toxic and immunomodulating. The antitumour activity of an ADEPT system using antibody delivered alcohol dehydrogenase (ADH) to convert ethanol to acetaldehyde inside cancer cells has been investigated. In vitro experiments confirmed the toxicity of acetaldehyde to a variety of tumour cell lines. The growth of daudi lymphoma cells can be suppressed when exposed to acetaldehyde. Adenocarcinoma cells appeared to be less sensitive to CMT-64 cells. After treatment with an ADEPT containing the human ADH beta 2, the number of CMT-64 cells exposed to ethanol reduced. In a preclinical model with Ad-ADH CMT-64 cells, mice that daily exposed to pulses of ethanol formed smaller tumour volume. The ability of this easily administered ADEPT system to produce significant effects on cell proliferation suggests that further optimized development is warranted.

Equipped with world-leading technology platforms and professional scientific staff, Creative Biolabs is committed to assisting our clients with the most satisfactory prodrug-Alcohol for ADEPT development. We also provide various ADEPT related services and products. Please contact us for more information and a detailed quote.

Reference

  1. Garaycoechea, J. I.; Patel, K. J. Why does the bone marrow fail in fanconi anemia? Blood. 2013, 123(1), 26-34.

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