Therapeutic Strategies to Target the Androgen Receptor

July 2022 in “ Journal of Medicinal Chemistry ”

Weiguo Xiang, Shaomeng Wang

TLDR Therapies targeting the androgen receptor are being developed to treat prostate cancer and improve bone and muscle health.

The document reviewed therapeutic strategies targeting the androgen receptor (AR), which is crucial for muscle and bone maintenance, male sexual functions, and prostate cancer progression. AR agonists were used to treat bone loss and muscle atrophy, while AR antagonists were developed for prostate cancer, including metastatic castration-resistant prostate cancer (mCRPC). Selective AR degraders (SARDs) and heterobifunctional degrader molecules were also explored, with four compounds in clinical development for prostate cancer treatment. The review summarized various compounds targeting AR and highlighted current research frontiers in this therapeutic area.

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A Phase IIA Randomized, Placebo-Controlled Clinical Trial to Study the Efficacy and Safety of the Selective Androgen Receptor Modulator (SARM), MK-0773 in Female Participants with Sarcopenia

research A Phase IIA Randomized, Placebo-Controlled Clinical Trial to Study the Efficacy and Safety of the Selective Androgen Receptor Modulator (SARM), MK-0773 in Female Participants with Sarcopenia

211 citations , May 2013 in “Journal of Nutrition Health & Aging”

MK-0773 safely increased muscle mass but did not improve muscle strength or function in elderly women with sarcopenia.

research Clinical Biochemistry of Dihydrotestosterone

50 citations , February 2013 in “Annals of Clinical Biochemistry”

Understanding how DHT works is important for diagnosing and treating hormone-related disorders.

research Pantolactams as Androgen Receptor Antagonists for the Topical Suppression of Sebum Production

5 citations , September 2011 in “Bioorganic & Medicinal Chemistry Letters”

Pfizer found that pantolactam-based compounds can reduce sebum (skin oil) production when applied topically.

Rational Design of a Topical Androgen Receptor Antagonist for the Suppression of Sebum Production with Properties Suitable for Follicular Delivery

research Rational Design of a Topical Androgen Receptor Antagonist for the Suppression of Sebum Production with Properties Suitable for Follicular Delivery

11 citations , May 2010 in “Journal of Medicinal Chemistry”

A new compound was created in 2010 that can control oil production when applied to the skin, and its effects are completely reversible after two weeks.

research Diphenyl Ethers as Androgen Receptor Antagonists for the Topical Suppression of Sebum Production

7 citations , April 2009 in “Bioorganic & Medicinal Chemistry Letters”

Diphenyl ethers can potentially reduce excess oil production when applied on the skin, helping treat conditions like acne.

4-(Alkylthio)- and 4-(Arylthio)-Benzonitrile Derivatives as Androgen Receptor Antagonists for the Topical Suppression of Sebum Production

research 4-(Alkylthio)- and 4-(Arylthio)-Benzonitrile Derivatives as Androgen Receptor Antagonists for the Topical Suppression of Sebum Production

11 citations , March 2009 in “Bioorganic & Medicinal Chemistry Letters”

Chemicals called 4-(alkylthio)- and 4-(arylthio)-benzonitrile derivatives can potentially reduce oil production on skin, which could help treat conditions like acne and hair loss.

research Rational Design and Synthesis of 4-((1R,2R)-2-Hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile (PF-998425), a Novel, Nonsteroidal Androgen Receptor Antagonist Devoid of Phototoxicity for Dermatological Indications

23 citations , October 2008 in “Journal of medicinal chemistry”

PF-998425 is a new, effective, and non-phototoxic treatment for skin conditions related to androgens.

research Pharmacology of Anabolic Steroids

441 citations , May 2008 in “British Journal of Pharmacology”

Anabolic steroids can build muscle and strength but have risks and need more research on their clinical benefits and side effects.

(1R,2S)-4-(2-Cyano-Cyclohexyl-Oxy)-2-Trifluoromethyl-Benzonitrile, A Potent Androgen Receptor Antagonist For Stimulating Hair Growth And Reducing Sebum Production

research (1R,2S)-4-(2-Cyano-Cyclohexyl-Oxy)-2-Trifluoromethyl-Benzonitrile, A Potent Androgen Receptor Antagonist For Stimulating Hair Growth And Reducing Sebum Production

14 citations , August 2007 in “Bioorganic & Medicinal Chemistry Letters”

The compound (1R,2S)-4-(2-Cyano-cyclohexyl-oxy)-2-trifluoromethyl-benzonitrile can stimulate hair growth and reduce oil production when applied topically.

Synthesis and Biological Evaluation of Amino-Pyridines as Androgen Receptor Antagonists for Stimulating Hair Growth and Reducing Sebum Production

research Synthesis and Biological Evaluation of Amino-Pyridines as Androgen Receptor Antagonists for Stimulating Hair Growth and Reducing Sebum Production

17 citations , August 2007 in “Bioorganic & Medicinal Chemistry Letters”

A compound made by Pfizer can potentially stimulate hair growth and reduce oil production, making it a good candidate for topical use.

Preparation of 4-Aryl-2-Trifluoromethylbenzonitrile Derivatives as Androgen Receptor Antagonists for Topical Suppression of Sebum Production

research Preparation of 4-Aryl-2-Trifluoromethylbenzonitrile Derivatives as Androgen Receptor Antagonists for Topical Suppression of Sebum Production

11 citations , August 2007 in “Bioorganic & Medicinal Chemistry Letters”

Scientists made a chemical (compound 4e) that can be applied on skin to reduce oil production, which can help with acne, but it might cause skin sensitivity to light.

research Design, Synthesis, and Biological Characterization of Metabolically Stable Selective Androgen Receptor Modulators

129 citations , January 2004 in “Journal of medicinal chemistry”

Researchers developed new compounds that target the androgen receptor effectively with fewer side effects.

research Current Aspects of Antiandrogen Therapy in Women

20 citations , January 1999 in “Current Pharmaceutical Design”

Antiandrogen therapy is effective and well tolerated for treating women's androgenic disorders like hirsutism, acne, and hair loss.

Preliminary Pharmacokinetics and Metabolism of Novel Non-Steroidal Antiandrogens in the Rat: Relation of Their Systemic Activity to the Formation of a Common Metabolite

research Preliminary Pharmacokinetics and Metabolism of Novel Non-Steroidal Antiandrogens in the Rat: Relation of Their Systemic Activity to the Formation of a Common Metabolite

16 citations , October 1994 in “The Journal of Steroid Biochemistry and Molecular Biology”

Two non-steroidal antiandrogens, RU 58841 and RU 56187, form a common metabolite at different rates, which may influence their effects; RU 56187 could be used for prostate cancer treatment and RU 58841 for acne treatment.

research RU 58841, A New Specific Topical Antiandrogen: A Candidate of Choice for the Treatment of Acne, Androgenetic Alopecia, and Hirsutism

49 citations , January 1994 in “The Journal of Steroid Biochemistry and Molecular Biology”

RU 58841 may treat acne, hair loss, and excessive hair growth.