Topilutamide

Last updated
Topilutamide
Topilutamide.svg
Clinical data
Trade names Eucapil
Other namesFluridil; BP-766
Routes of
administration 		Topical [1] [2] [3] [4] [5]
Drug class Nonsteroidal antiandrogen
ATC code
  • None
Identifiers
  • 2-hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-[(2,2,2-trifluoroacetyl)amino]propanamide
CAS Number
PubChem CID
ChemSpider
UNII
ECHA InfoCard 100.245.367 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C13H11F6N3O5
Molar mass 403.237 g·mol−1
3D model (JSmol)
  • C[C@@](CNC(=O)C(F)(F)F)(C(=O)NC1=CC(=C(C=C1)[N+](=O)[O-])C(F)(F)F)O
  • InChI=1S/C13H11F6N3O5/c1-11(25,5-20-10(24)13(17,18)19)9(23)21-6-2-3-8(22(26)27)7(4-6)12(14,15)16/h2-4,25H,5H2,1H3,(H,20,24)(H,21,23)/t11-/m1/s1
  • Key:YCNCRLKXSLARFT-LLVKDONJSA-N

Topilutamide, known more commonly as fluridil and sold under the brand name Eucapil, is an antiandrogen medication which is used in the treatment of pattern hair loss in men and women. [6] [1] [2] [3] [4] [5] It is used as a topical medication and is applied to the scalp. [1] [2] [3] [4] [5] Topilutamide belongs to a class of molecules known as perfluoroacylamido-arylpropanamides. [6]

Contents

Topilutamide is a nonsteroidal antiandrogen (NSAA), or an antagonist of the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT). [1] [2] [3] [4] [5]

Topilutamide was introduced for medical use in 2003. [7] It is marketed only in the Czech Republic and Slovakia. [8] The patent for Topilutamide expired in 2020. [6]

Medical uses

Topilutamide is used as a topical medication in the treatment of pattern hair loss in men and women. [1] [2] [3] [4] [5] Topilutamide is approved for cosmetic use in Europe but has not received FDA approval nor approval by the EMA for the treatment of androgenetic alopecia. [8] Finasteride and Minoxidil are currently the only treatments approved for the treatment of this condition. [2]

Available forms

Under the brand name Eucapil, topilutamide is available as a 2% topical formulation intended for application to the scalp. [4]

Pharmacology

Pharmacodynamics

Topilutamide is an antagonist of the AR, the biological target of androgens like testosterone and DHT. [1] [2] [3] [4] [5] Fluridil binds to the androgen receptor with approximately a 9-15-fold higher affinity than more primitive NSAAs such as bicalutamide and hydroxyflutamide, but more research is required to validate these findings. [6]

Percentage androgen receptor suppression in LNCaP Cells after 48-h Drug Incubation via Western Blot [6]
Compound3 μM10 μM
BP-766 (Topilutamide)41 ± 595.9 ± 6
BP-52162 ± 7100
BP-343 ± 42 ± 2
Bicalutamide3 ± 311 ± 3
Hydroxyflutamide2 ± 66 ± 7

Pharmacokinetics

Topilutamide is a topical medication and is applied to the scalp. [1] [2] [3] [4] [5] Topilutamide degrades in human serum at 37 °C with a half-life of approximately 6 hours and is undetectable after 48 hours. [6] Perfluoroacylamido-arylpropanamides decompose hydrolytically to BP-34 and their corresponding perfluorocarboxylic acid. [6] In the case of topilutamide, that perfluorocarboxylic acid is trifluoroacetic acid. [6] The two metabolites of topilutamide namely BP-34 and trifluoroacetic acid were undetectable in human serum (below the detection limit of 5 ng/mL) along with the parent compound topilutamide, in human studies. [6] BP-34 was shown to be devoid of anti-androgenic activity. [6]

Chemistry

Topilutamide is a nonsteroidal compound and is closely related to other NSAAs such as flutamide and bicalutamide. [7]

History

Topilutamide was introduced for medical use in 2003. [7]

Society and culture

Generic names

Topilutamide is the generic name of the drug and its INN Tooltip International Nonproprietary Name. [9] [10] [11] It is also known more commonly as fluridil. [6] Topilutamide is also known by its former developmental code name BP-766. [6]

Brand names

Topilutamide is marketed by Interpharma Praha under the brand name Eucapil. [7] [3]

Availability

Topilutamide is available only in Europe in the Czech Republic and Slovakia. [8]

See also

Related Research Articles

<span class="mw-page-title-main">Antiandrogen</span> Class of pharmaceutical drugs

Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. They can be thought of as the functional opposites of AR agonists, for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens.

<span class="mw-page-title-main">Ketoconazole</span> Antifungal chemical compound

Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candidiasis, pityriasis versicolor, dandruff, and seborrheic dermatitis. Taken by mouth it is a less preferred option and only recommended for severe infections when other agents cannot be used. Other uses include treatment of excessive male-patterned hair growth in women and Cushing's syndrome.

<span class="mw-page-title-main">Finasteride</span> Antiandrogen medication

Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat pattern hair loss and benign prostatic hyperplasia (BPH) in men. It can also be used to treat excessive hair growth in women. It is usually taken orally but there are topical formulations for patients with hair loss, designed to minimize systemic exposure by acting specifically on hair follicles.

<span class="mw-page-title-main">Bicalutamide</span> Prostate cancer treatment

Bicalutamide, sold under the brand name Casodex among others, is an antiandrogen medication that is primarily used to treat prostate cancer. It is typically used together with a gonadotropin-releasing hormone (GnRH) analogue or surgical removal of the testicles to treat metastatic prostate cancer (mPC). To a lesser extent, it is used at high doses for locally advanced prostate cancer (LAPC) as a monotherapy without castration. Bicalutamide was also previously used as monotherapy to treat localized prostate cancer (LPC), but authorization for this use was withdrawn following unfavorable trial findings. Besides prostate cancer, bicalutamide is limitedly used in the treatment of excessive hair growth and scalp hair loss in women, as a puberty blocker and component of feminizing hormone therapy for transgender girls and women, to treat gonadotropin-independent early puberty in boys, and to prevent overly long-lasting erections in men. It is taken by mouth.

<span class="mw-page-title-main">5α-Reductase inhibitor</span> Class of medications

5α-Reductase inhibitors (5-ARIs), also known as dihydrotestosterone (DHT) blockers, are a class of medications with antiandrogenic effects which are used primarily in the treatment of enlarged prostate and scalp hair loss. They are also sometimes used to treat excess hair growth in women and as a component of hormone therapy for transgender women.

The management of hair loss, includes prevention and treatment of alopecia, baldness, and hair thinning, and regrowth of hair.

<span class="mw-page-title-main">Flutamide</span> Chemical compound

Flutamide, sold under the brand name Eulexin among others, is a nonsteroidal antiandrogen (NSAA) which is used primarily to treat prostate cancer. It is also used in the treatment of androgen-dependent conditions like acne, excessive hair growth, and high androgen levels in women. It is taken by mouth, usually three times per day.

<span class="mw-page-title-main">Pattern hair loss</span> Medical condition

Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front hairline, loss of hair on the crown (vertex) of the scalp, or a combination of both. Female-pattern hair loss (FPHL) typically presents as a diffuse thinning of the hair across the entire scalp.

Non scarring hair loss, also known as noncicatricial alopecia is the loss of hair without any scarring being present. There is typically little inflammation and irritation, but hair loss is significant. This is in contrast to scarring hair loss during which hair follicles are replaced with scar tissue as a result of inflammation. Hair loss may be spread throughout the scalp (diffuse) or at certain spots (focal). The loss may be sudden or gradual with accompanying stress.

<span class="mw-page-title-main">Alfatradiol</span> Medication

Alfatradiol, also known as 17α-estradiol and sold under the brand names Avicis, Avixis, Ell-Cranell Alpha, and Pantostin, is a weak estrogen and 5α-reductase inhibitor medication which is used topically in the treatment of pattern hair loss in men and women. It is a stereoisomer of the endogenous steroid hormone and estrogen 17β-estradiol.

<span class="mw-page-title-main">RU-58642</span> Chemical compound

RU-58642 is a nonsteroidal antiandrogen (NSAA) derived from nilutamide with very high affinity and selectivity for the androgen receptor (AR), which made it among the most potent and efficacious antiandrogens known at the time of its discovery. It was investigated for topical application for the treatment of androgenetic alopecia, but development did not proceed past initial trial stages, and it is now only used for scientific research into the AR.

<span class="mw-page-title-main">RU-58841</span> Chemical compound

RU-58841, also known as PSK-3841 or HMR-3841, is a nonsteroidal antiandrogen (NSAA) which was initially developed in the 1980s by Roussel Uclaf, the French pharmaceutical company from which it received its name. It was formerly under investigation by ProStrakan for potential use as a topical treatment for androgen-dependent conditions including acne, pattern hair loss, and excessive hair growth. The compound is similar in structure to the NSAA RU-58642 but contains a different side-chain. These compounds are similar in chemical structure to nilutamide, which is related to flutamide, bicalutamide, and enzalutamide, all of which are NSAAs similarly. RU-58841 can be synthesized either by building the hydantoin moiety or by aryl coupling to 5,5-dimethylhydantoin.

<span class="mw-page-title-main">Nonsteroidal antiandrogen</span> Antiandrogen with a nonsteroidal chemical structure

A nonsteroidal antiandrogen (NSAA) is an antiandrogen with a nonsteroidal chemical structure. They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the effects of androgens like testosterone and dihydrotestosterone (DHT). NSAAs are used in the treatment of androgen-dependent conditions in men and women. They are the converse of steroidal antiandrogens (SAAs), which are antiandrogens that are steroids and are structurally related to testosterone.

<span class="mw-page-title-main">Cioteronel</span> Chemical compound

Cioteronel is a nonsteroidal antiandrogen (NSAA) that was never marketed. It was under development between 1989 and 2001 for the topical treatment of androgenetic alopecia, and acne and for the oral treatment of benign prostatic hyperplasia; it reached phase III clinical trials for acne and phase II studies for androgenetic alopecia, but was ultimately discontinued due to poor efficacy.

<span class="mw-page-title-main">Trimethyltrienolone</span> Chemical compound

Trimethyltrienolone (TMT), also known by its developmental code name R-2956 or RU-2956, is an antiandrogen medication which was never introduced for medical use but has been used in scientific research.

<span class="mw-page-title-main">Steroidal antiandrogen</span> Class of compounds

A steroidal antiandrogen (SAA) is an antiandrogen with a steroidal chemical structure. They are typically antagonists of the androgen receptor (AR) and act both by blocking the effects of androgens like testosterone and dihydrotestosterone (DHT) and by suppressing gonadal androgen production. SAAs lower concentrations of testosterone through simulation of the negative feedback inhibition of the hypothalamus. SAAs are used in the treatment of androgen-dependent conditions in men and women, and are also used in veterinary medicine for the same purpose. They are the converse of nonsteroidal antiandrogens (NSAAs), which are antiandrogens that are not steroids and are structurally unrelated to testosterone.

The medical uses of bicalutamide, a nonsteroidal antiandrogen (NSAA), include the treatment of androgen-dependent conditions and hormone therapy to block the effects of androgens. Indications for bicalutamide include the treatment of prostate cancer in men, skin and hair conditions such as acne, seborrhea, hirsutism, and pattern hair loss in women, high testosterone levels in women, hormone therapy in transgender women, as a puberty blocker to prevent puberty in transgender girls and to treat early puberty in boys, and the treatment of long-lasting erections in men. It may also have some value in the treatment of paraphilias and hypersexuality in men.

<span class="mw-page-title-main">RU-59063</span> Chemical compound

RU-59063 is a nonsteroidal androgen or selective androgen receptor modulator (SARM) which was first described in 1994 and was never marketed. It was originally thought to be a potent antiandrogen, but subsequent research found that it actually possesses dose-dependent androgenic activity, albeit with lower efficacy than dihydrotestosterone (DHT). The drug is an N-substituted arylthiohydantoin and was derived from the first-generation nonsteroidal antiandrogen (NSAA) nilutamide. The second-generation NSAAs enzalutamide, RD-162, and apalutamide were derived from RU-59063.

<span class="mw-page-title-main">Pyrilutamide</span> Chemical compound

Pyrilutamide is a nonsteroidal antiandrogen (NSAA) – specifically, a selective high-affinity silent antagonist of the androgen receptor (AR) – which is under development by Suzhou Kintor Pharmaceuticals, inc., a subsidiary of Kintor Pharmaceutical Limited, for the potential treatment of androgenic alopecia As of October 2022, it is in phase 3 clinical trials for androgenic alopecia and phase 2 trials for acne.

References

  1. 1 2 3 4 5 6 7 Sovak M, Seligson AL, Kucerova R, Bienova M, Hajduch M, Bucek M (August 2002). "Fluridil, a rationally designed topical agent for androgenetic alopecia: first clinical experience". Dermatologic Surgery. 28 (8): 678–85. doi:10.1046/j.1524-4725.2002.02017.x. PMID   12174057. S2CID   36439600.
  2. 1 2 3 4 5 6 7 8 Haber RS, Stough DB (2006). Hair Transplantation. Elsevier Health Sciences. pp. 7–. ISBN   1-4160-3104-9.
  3. 1 2 3 4 5 6 7 8 Scripta Medica. 2006. pp. 45, 53–54. Fluridil was developed as a topical antiandrogen, suitable for the treatment of hyperandrogenic skin syndromes. The cosmetic product Eucapil® containing 2% fluridil in isopropanol was tested in women with AGA in a 9-month open study. [...] In a clinical study conducted at our facility, fluridil in solution (Eucapil®, Interpharma Praha, Czech Republic) has been shown to be effective and safe in the treatment of men with androgenetic alopecia (30, 31).
  4. 1 2 3 4 5 6 7 8 Avram MR, Rogers NE (30 November 2009). Hair Transplantation. Cambridge University Press. pp. 11–. ISBN   978-1-139-48339-1.
  5. 1 2 3 4 5 6 7 Kirby RS, Carson CC, Kirby MG, White A (29 January 2009). Men's Health, Third Edition. CRC Press. pp. 362–. ISBN   978-1-4398-0807-8.
  6. 1 2 3 4 5 6 7 8 9 10 11 12 Seligson AL, Campion BK, Brown JW, Terry RC, Kucerova R, Bienova M, Hajduch M, Sovak M (2003). "Development of fluridil, a topical suppressor of the androgen receptor in androgenetic alopecia". Drug Development Research. 59 (3): 292–306. doi:10.1002/ddr.10166. ISSN   0272-4391. S2CID   98640343.
  7. 1 2 3 4 Hermkens PH, Kamp S, Lusher S, Veeneman GH (July 2006). "Non-steroidal steroid receptor modulators". IDrugs. 9 (7): 488–94. doi:10.2174/0929867053764671. PMID   16821162.
  8. 1 2 3 "Androgenetic Alopecia,Hair loss,Eucapil". www.eucapil.com.
  9. ↑ Chambers M. "ChemIDplus - 260980-89-0 - YCNCRLKXSLARFT-UHFFFAOYSA-N - Topilutamide [INN] - Similar structures search, synonyms, formulas, resource links, and other chemical information". chem.nlm.nih.gov.
  10. ↑ "Microsoft Word - final_PL91.doc" (PDF). Retrieved 2018-10-04.
  11. ↑ United States International Trade Commission (2008). Modifications to the Harmonized Tariff Schedule of the United States to Implement the Dominican Republic-Central America-United States Free Trade Agreement With Respect to Costa Rica. DIANE Publishing. pp. 18–. ISBN   978-1-4578-1723-6.
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