Small Molecule-Based Cancer Drugs

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Molecule is the smallest particle that can exist in free state. The smallest particle of a substance that retains the chemical and physical properties of the substance and is composed of two or more atoms; a group of like or different atoms held together by chemical forces. Small molecules are a diverse group of natural and synthetic substances that generally have a low molecular weight. They are either isolated from natural sources such as plants, fungi or microbes, or they are synthesized by organic chemistry. Most conventional pharmaceuticals, such as aspirin, penicillin, and chemotherapeutics, are small molecules.

Small molecules can be kinase inhibitor, antiangiogeneses agent, and others. Most of them are already illustrated in an appropriate class. Those can not be classified and are shown in the Table 12. Small molecule kinase inhibitor is one of most successful anti-cancer drugs. Several drugs, such as, Gleevec, Iressa, Nexavar, Sutent. and Tarceva, are in the market for different cancer indications.

Flavopiridol is a small molecule derivative of the alkaloid rohitukine, which inhibits cyclin-dependent kinases causing a halt to cell cycle. MLN944 (XR5944) is a novel small molecule with DNA activity. The primary mechanism of action of MLN944 likely involves DNA binding and intercalation.

Telcyta (TLK286) is a small molecule activated by glutathione S-transferase P1-1 (GST P1-1), an enzyme present in higher levels in many human cancers than in normal tissues. Activation of Telcyta occurs when GST P1-1 splits Telcyta into two active fragments: a glutathione analog fragment and an active cytotoxic fragment. The cytotoxic fragment reacts with important cell components, including RNA, DNA and proteins, leading to cell death.

Telintra (TLK199), a small molecule bone marrow stimulant, is in a Phase II trial in myelodysplastic syndrome, a form of pre-leukemia.