Mechanisms of action and potential therapeutic uses of thalidomide (original) (raw)

Thalidomide: A Banned Drug Resurged into Future Anticancer Drug

Current Drug Therapy, 2012

In 1956, (±)-thalidomide was introduced into the market in Europe as sedative and drug for morning sleeping sickness which resulted into a tragedy called thalidomide tragedy (softenon drama) due to its teratogenic effects in newly born babies. Thalidomide was banned all over the world due to this havoc, which was a big breakdown in the history of this drug. But, in 1998 it resurged after US, FDA approved it for treating Erythema Leprosum Nodosum (ENL). Besides, recently thalidomide and its derivatives showed remarkable property for controlling several malignancies. Thalidomide and its analogues have been used for treating metastatic prostate cancer, multiple myeloma, HIV-related ulcers, Kaposi's sarcoma, weight loss and body wasting associated with HIV. The present article describes the sate-of-art of thalidomide applications with special emphasis on pharmacology, pharmacokinetics, breakdown in the history, break through and resurgence, potential future anticancer drug, potencies of thalidomide vs its analogues, mechanism of anticancer action, different stages and toxicity management. Besides, efforts were also made to predict the future perspectives of thalidomide and its analogues.

Thalidomide: from tragedy to promise

Swiss Medical Weekly, 2003

Thalidomide is an immunomodulatory and antiangiogenic drug. Although the exact mechanism of action is not fully understood, it has been shown to be active in a variety of diseases. There are multiple trials going on to evaluate the optimal dose of thalidomide and the importance of combining thalidomide with other drugs. This review introduces the properties and putative mechanism of action of thalidomide and summarizes the most important clinical trials with this biological modifier.

Thalidomide–A Notorious Sedative to a Wonder Anticancer Drug

Current Medicinal Chemistry, 2013

In the past 50 years, thalidomide has undergone a remarkable metamorphosis from a notorious drug inducing birth defects into a highly effective therapy for treating leprosy and multiple myeloma. Today, most notably, thalidomide and its analogs have shown efficacy against a wide variety of diseases, including inflammation and cancer. The mechanism underlying its teratogenicity as well as its anticancer activities has been intensively studied. This review summarizes the biological effects and therapeutic uses of thalidomide and its analogs, and the underlying mechanisms of thalidomide's action with a focus on its suppression of tumor growth.

Forgive sins: rise of thalidomide

Our Dermatology Online, 2014

Thalidomide was originally used as a Wonder Drug to treat morning sickness and insomnia in pregnant women in late 1950s. It became apparent in early 1960s that thalidomide treatment resulted in severe birth defects in thousands of children. Then it was banned in most of countries. Later on discovered anti-inflammatory and anti-angiogenic properties of Thalidomide proved to be useful for treatment of leprosy and multiple myeloma. A series of immunomodulatory drugs created by chemical modification of thalidomide have been developed to overcome the original devastating side effects. It’s being investigated extensively as a treatment for many other severe cutaneous disorders and advanced cancers. We briefly review pharmacological and the therapeutic profile of thalidomide.

The rise, fall and subsequent triumph of thalidomide: lessons learned in drug development

Therapeutic advances in hematology, 2011

Perhaps no other drug in modern medicine rivals the dramatic revitalization of thalidomide. Originally marketed as a sedative, thalidomide gained immense popularity worldwide among pregnant women because of its effective anti-emetic properties in morning sickness. Mounting evidence of human teratogenicity marked a dramatic fall from grace and led to widespread social, legal and economic ramifications. Despite its tragic past thalidomide emerged several decades later as a novel and highly effective agent in the treatment of various inflammatory and malignant diseases. In 2006 thalidomide completed its remarkable renaissance becoming the first new agent in over a decade to gain approval for the treatment of plasma cell myeloma. The catastrophic collapse yet subsequent revival of thalidomide provides important lessons in drug development. Never entirely abandoned by the medical community, thalidomide resurfaced as an important drug once the mechanisms of action were further studied and...

Thalidomide: The journey from curse to boon

World Journal of Biology Pharmacy and Health Sciences

The tragic spectacle of thousands of infants born with deformed arms and legs at the beginning of the 1960s stunned the entire globe. The public's memory has been permanently scarred by the sight of those young people struggling with limb deformities. The medicine thalidomide, which pregnant women use for morning sickness and insomnia, was found to be responsible for the deformities in limbs and other organs. Thalidomide was sold in over 40 nations and was authorised for prescription usage in Canada from April 1961 to March 1962. Although the true number was likely greater due to spontaneous miscarriages and stillbirths, it resulted in around 115 occurrences of deformities in this country.Due to its expulsion from the medical toolbox, this medication became a term of demeaning for many years. However, thalidomide has emerged from the darkness of unimaginable tragedy. Though under stringent restrictions, it has made a remarkable recovery and entered the current therapeutic regime...

Thalidomide and Its Analogs as Anticancer Agents

Thalidomide has reemerged as a promising anticancer and anti-inflammatory drug despite its devastating congenital birth defects. Many thalidomide derivatives with enhanced antiangiogenic and immunomodulatory effects or greater cytokine inhibition accompanied by less adverse toxicities than the parent drug have been developed. The mechanisms of action of thalidomide and its analogs are complex and not yet fully understood, but studies indicate that their antiangiogenic and immunomodulatory effects play important roles. Thalidomide and lenalidomide have been approved for the treatment of multiple myeloma and myelodysplastic syndrome. The powerful antiangiogenic, anti-inflammatory, and apoptotic effects mean that thalidomide and its immunomodulatory derivatives will continue to be explored in the treatment of a variety of cancers and inflammatory diseases. [Tzu Chi Med J 2008;20(3):188-195] Article Info