Maxim issued with novel cancer drug patent

The development of caspase cascade activators and inducer of apoptosis is a highly desirable goal in the development of therapeutically effective antineoplastic agents. Since autoimmune disease and certain degenerative diseases also involve the proliferation of abnormal cells, therapeutic treatment for these diseases could also involve the enhancement of the apoptotic process through the administration of appropriate caspase cascade activators and inducers of apoptosis.

The issuance of this patent is the latest development in Maxim​'s research and development into therapies for tumour growth and proliferation. Maxim's MX2407 anticancer drug candidate is part of a novel class of microtubule inhibitors demonstrating promising vascular targeting activity with potent antitumour activity in pre-clinical in vitro and in vivo studies.

MX2407 appeared highly effective in mouse tumour models, producing tumour necrosis at doses that correspond to only 25 per cent of the maximum tolerated dose. Moreover, in combination treatment, MX2407 significantly enhanced the antitumour activity of the chemotherapeutic cisplatin, resulting in tumour-free animals.

The US patent (6,906,203), entitled: "Substituted 4H-Chromene and Analogs as Activators of Caspases and Inducers of Apoptosis and the Use Thereof," describes the substitution of 4H-chromene and analogs, two known activators of caspases and inducers of apoptosis. The invention also relates to the use of these compounds as therapeutically effective anti-cancer agents.

Cancerous cells often exhibit unchecked growth caused by the disabling or absence of the natural process of programmed cell death called apoptosis. Apoptosis is normally triggered to destroy a cell from within when it outlives its purpose or it is seriously damaged. One of the most promising approaches in the fight against cancer is to selectively induce apoptosis in cancer cells, thereby checking, and perhaps reversing, the improper cell growth.

Chemical genetics is a research approach investigating the effect of small molecule drug candidates on the cellular activity of a protein, enabling researchers to determine the protein's function. The focus on apoptosis is achieved by screening for the activity of caspase-3, an enzyme with an essential role in cleaving other important proteins necessary to cause cell death through apoptosis.

Apoptosis and caspases are thought to be crucial in the development of cancer. There is mounting evidence that cancer cells, while containing caspases, lack parts of the molecular machinery that activates the caspase cascade.

This makes the cancer cells lose their capacity to undergo cellular suicide and the cells become immortal, i.e. cancerous. In the case of the apoptosis process, control points are known to exist that represent points for intervention leading to activation.

It has been shown that chemotherapeutic (anti-cancer) drugs can trigger cancer cells to undergo suicide by activating the dormant caspase cascade. This may be a crucial aspect of the mode of action of most, if not all, known anticancer drugs. The mechanism of action of current antineoplastic drugs frequently involves an attack at specific phases of the cell cycle.

During multiplication, cells progress to a stage in which DNA synthesis occurs, termed S. Later, cell division, or mitosis occurs, in a phase called M. Antineoplastic drugs such as cytosine arabinoside, hydroxyurea, 6-mercaptopurine, and methotrexate are S phase specific, whereas antineoplastic drugs such as vincristine, vinblastine, and paclitaxel are M phase specific.

Many slow growing tumours, for example colon cancers, exist primarily in the Go phase, whereas rapidly proliferating normal tissues, for example bone marrow, exist primarily in the S or M phase. Thus, a drug like 6-mercaptopurine can cause bone marrow toxicity while remaining ineffective for a slow growing tumour.