List of 5α-reductase inhibitors

This is a list of 5α-reductase inhibitors (5α-RIs), drugs which inhibit one or more isoforms of the enzyme 5α-reductase. This enzyme is responsible for the conversion of the androgen hormone testosterone into the more potent dihydrotestosterone (DHT) and is essential for the production of neurosteroids like allopregnanolone, tetrahydrodeoxycorticosterone (THDOC), and 3α-androstanediol from progesterone, deoxycorticosterone, and DHT, respectively. 5α-Reductase inhibitors have medical applications in the treatment of benign prostatic hyperplasia, androgenic alopecia (pattern hair loss), and hirsutism (excessive hair growth).

Pharmaceutical drugs

5α-RIs that are used in medicine include the following:

• Alfatradiol (Ell-Cranell Alpha, Pantostin)
• Dutasteride (Avodart) – inhibits types 1, 2, and 3
• Epristeride (Aipuliete, Chuanliu) – inhibits type 2
• Finasteride (Proscar, Propecia) – inhibits types 2 and 3
• Saw palmetto extract (Permixon) – inhibits types 1 and 2

Experimental drugs

5α-RIs that were under development for potential clinical use but were never marketed or are used in research include the following:

• 4-MA – inhibits types 1 and 2 (IC₅₀ = 8.5 nM), but also 3β-HSD inhibitor, investigated extensively but found to be hepatotoxic^[1]
• 17β-Carboxy-4-androsten-3-one^[2][3]
• AS-97004
• Azelaic Acid^[4]
• Bexlosteride (LY-300502) – inhibits type 1
• CGP-53153
• Efomycin G (SNA 4606-2)
• EM-402
• FCE-28260 – inhibits types 1 and 2
• FK-143
• FR-146687
• G-20000
• Izonsteride (LY-320236) – inhibits types 1 and 2
• L-10
• L-39
• L-697818
• L-751788 (16-((4-chlorophenyl)oxy)-4,7-dimethyl-4-azaandronstan-3-one)
• Lapisteride (CS-891) – inhibits types 1 and 2
• LY-191704
• LY-266111
• MK-386 (L-733692) – inhibits type 1
• MK-434 – inhibits type 2^[5]
• MK-963 (L-654066) – inhibits type 2
• ONO-3805 (ONO-RI-3805)
• PHL-00801 (Prostatonin; PY 102/UR 102; Pygeum africanum/Urtica dioica extract)
• PNU-157706 – inhibits types 1 and 2^[6]
• Steroidal oximes^[7][8]
• Turosteride (FCE-26073) – inhibits type 2 and to a 15-fold lesser extent type 1
• Z-350 – also an α₁-adrenergic receptor antagonist^[9]

Herbs and other inhibitors

Many plants, as well as their associated phytochemical constituents, have inhibitory effects on 5α-reductase.^[10] In addition, many of these compounds are also phytoestrogens.^[11] Examples include the following:

• Zinc.^[12]
• Riboflavin (vitamin B2).^[13]
• Azelaic acid,^[12] (sometimes combined with minoxidil hair solution).
• β-Sitosterol,^[14] is just one of the many phytosterols.
• Polyphenols^[15]
• Alizarin,
• Curcumin, the principal curcuminoid of turmeric.
• Green tea catechins, including (-)-epicatechin-3-gallate, and (-)-epigallo-catechin-3-gallate (EGCG).^[16]
• Valoneic acid dilactone and gallagyldilactone are two hydrolysable tannin polyphenols isolated from the heartwood of Shorea laeviforia^[17] and oaks species such as the North American white oak (Quercus alba) and European red oak (Quercus robur) are inhibitory.^[18]
• Angelica koreana ^[19][20]
• Garden Balsam or Rose Balsam (Impatiens balsamina)^[21]
• Pollen of Turnip, turnip rape, fast plants, field mustard, or turnip mustard (Brassica rapa)^[22]
• Dodder (Cuscuta reflexa)^[23]
• Euphorbia jolkinii^[24][25]
• Lingzhi mushroom or Reishi mushroom (Ganoderma lucidum)^{[26][27][28][29]}
  • Ganoderic acid,^[30] or Ganoderol B are thought to be the compounds in the mushroom that are specifically active.^[31]
• Chinese Knotweed (Polygonum multiflorum),^[32] contains resveratrol-like Stilbenoids.
• Black Pepper leaf extract (Piper nigrum) ^[33]
• Red Stinkwood (Pygeum africanum)^[34]
• Saw Palmetto (Serenoa repens, active substance possibly lauric acid^[35])^[36][37]
  • The berries of saw palmetto (Serenoa repens), a small palm native to the south east United States, possess a dual 5a-reductase inhibition activity, due to their high content of phytosterols: β-sitosterol, stigmasterol, lupeol, lupenone, and cycloartenol. Permixon® was launched in Europe in 1984 but has no FDA approval. The lipido-sterol extract markedly inhibits both the human isoenzymes. Type 1 isoenzyme is noncompetitively (Ki = 7.2 μg/mL) and type 2 isoenzyme uncompetitively (Ki = 4.9 μg/mL) inhibited^[38]
• Pine (Pinus sp. resin, active substance abietic acid)^[39]
• Ku Shen or Bitter root (Sophora flavescens)^[40]
• Japanese hedge parsley (Torilis japonica)^[41]
• Eastern Arborvitae, Northern Whitecedar (Thuja occidentalis)^[42]
• Spore of Japanese climbing fern (Lygodium japonicum)^[43]
• The relative inhibitory potencies of unsaturated fatty acids are, in decreasing order: Gamma-Linolenic acid, alpha-linolenic acid, linoleic acid, palmitoleic acid, oleic acid, and myristoleic acid.^[44]
  • Medium chain fatty acids such as those found in coconut and the kernel of many palm fruits have also been found to inhibit 5α-reductase.^[45]
• Certain pesticides are able to disturb the sex steroid hormone system and to act as antiandrogens.^[46]
• Amla(Phyllanthus emblica)^[47]

Herbs like Pyllanthus Emblica^[47] possess 5 alpha reductase inhibition properties and may decrease scalp dht when used topically, thereby facilitating new hair growth. Hence, extract of these herbs may be beneficial for Androgenic alopecia.

These supplements have limited testing in human clinical trials, and their potential for the treatment of BPH, androgenic alopecia, and related conditions is unknown.

References