How Was Dutasteride Developed?
If finasteride is based off of a tuber plant, what is dutasteride based off of? The same tuber?
As far as I know, GlaxoSmithKline (GSK) developed dutasteride… but my knowledge of its origin pretty much ends there. I’m not familiar with their processes of discovery.
I do know that dutasteride works in similar ways to finasteride and is used to treat certain prostate problems. Dutasteride is not yet approved for the treatment of male pattern baldness, though.
In the biopharmaceutical industry, when one compound (e.g., finasteride) is discovered and shown to be effective in clinical trials, medicinal chemists then synthetically create similar compounds based on structure-activity relationships in test tubes (termed “in vitro” work). They then test these compounds in animal (“preclinicalâ€) settings to see if it shows similar properties (in this case, inhibition of human 5 alpha-reductase and similar tissue distribution) and hopefully additional properties that can be beneficial (longer half-life, duration of action, better safety, etc) based on additional changes to the compound. An excellent (albeit very technical) summary of the discovery of both finasteride and dutasteride is at: https://www.ncbi.nlm.nih.gov/pubmed/16719800
Frye SV. Discovery and clinical development of dutasteride, a potent dual 5alpha-reductase inhibitor. Curr Top Med Chem. 2006;6(5):405-21.
As a side note, while finasteride has chemical similarities to compounds also found in many plants, it was also chemically synthesized by Merck scientists based on their belief that a drug that would reduce DHT levels would be beneficial for inhibiting prostate growth. Unlike some plants, which have many properties beyond (and also including) inhibition of DHT, Merck was able to chemically isolate the specific molecular basis for inhibition of DHT. So, unlike digitalis, which is a cardiac medication with a chemical structure highly similar to the foxglove plant, Digitalis purpurea, finasteride was synthesized based on a specific structure not found in the tuber (or other) plant per se.
finasteride wasn’t discovered in a tuber plant.
In 1974, Julianne Imperato-McGinley of Cornell Medical College in New York attended a conference on birth defects. She reported on a group of hermaphroditic children in the Caribbean who appeared sexually ambiguous at birth, and were initially raised as girls, but then grew external male genitalia and other masculine characteristic post-onset of puberty. Her research group found that these children shared a genetic mutation, causing deficiency of the 5α-reductase enzyme and male hormone dihydrotestosterone (DHT), which was found to have been the etiology behind abnormalities in male sexual development. Upon maturation, these individuals were observed to have smaller prostates which were underdeveloped, and were also observed to lack incidence of male pattern baldness.[47][48]
In 1975, copies of Imperato-McGinley’s presentation were seen by P. Roy Vagelos, who was then serving as Merck’s basic-research chief. He was intrigued by the notion that decreased levels of DHT led to the development of smaller prostates. Dr. Vagelos then sought to create a drug which could mimic the condition found in the pseudo-hermaphroditic children in order to treat older men who were suffering from benign prostatic hyperplasia.[49]
In 1992, finasteride (5 mg) was approved by the U.S. Food and Drug Administration (FDA) for treatment of benign prostatic hyperplasia (BPH), which Merck marketed under the brand name Proscar.
In 1997, Merck was successful in obtaining FDA approval for a second indication of finasteride (1 mg) for treatment of male pattern baldness (MPB), which was marketed under the brand name Propecia.
Eli
How about providing the references (47-49) or your source when you clearly cut and paste?
sorry md, forgot to post it.
MD: there you go. enjoy
https://emedicine.medscape.com/article/924291-overview
https://www.ishrs.org/articles/dutasteride-trials.htm
https://www.nytimes.com/1992/02/16/business/keeping-the-pipeline-filled-at-merck.html?src=pm
as mentioned I have no idea where people get the idea finasteride was found from tuber plants.