List of investigational sex-hormonal agents explained

This is a list of investigational sex-hormonal agents, or sex-hormonal agents that are currently under development for clinical use but are not yet approved. Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses.

This list was last comprehensively updated sometime between May 2017 and September 2021. It is likely to become outdated with time.

Androgenics

Androgen receptor agonists

• EC586 – oral prodrug of testosterone (androgen/anabolic steroid) with improved pharmacokinetics

Selective androgen receptor modulators

• DT-200 (G-100192, GLPG-0492) – selective androgen receptor modulator for Duchenne muscular dystrophy https://adisinsight.springer.com/drugs/800018432
• Enobosarm (ostarine; GTx-024, MK-2866; S-22; VERU-024) – selective androgen receptor modulator for breast cancer https://adisinsight.springer.com/drugs/800022562
• GSK-2881078 – selective androgen receptor modulator for cachexia https://adisinsight.springer.com/drugs/800039743
• OPK-88004 (LY-2452473; OPK-88004; TT-701) – selective androgen receptor modulator for benign prostatic hyperplasia, erectile dysfunction, and prostate cancer https://adisinsight.springer.com/drugs/800033580
• VK-5211 (LGD-4033; ligandrol) – selective androgen receptor modulator for hip fracture and muscle atrophy https://adisinsight.springer.com/drugs/800030373
• Vosilasarm (EP-0062, RAD-140; testolone) – selective androgen receptor modulator for breast cancer https://adisinsight.springer.com/drugs/800028398

Androgen receptor antagonists

• Bavdegalutamide (AVR-110) – androgen receptor antagonist for prostate cancerhttps://adisinsight.springer.com/drugs/800054393^[1] https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl125.pdf?sfvrsn=af269747_5&download=true
• Clascoterone (CB-03-01, Breezula, Winlevi) – androgen receptor antagonist for topical treatment of scalp hair loss http://adisinsight.springer.com/drugs/800026561
• Deutenzalutamide (deuterated enzalutamide; HC-1119) – androgen receptor antagonist for prostate cancer https://adisinsight.springer.com/drugs/800052304 https://www.dovepress.com/effect-of-n-methyl-deuteration-on-metabolism-and-pharmacokinetics-of-e-peer-reviewed-article-DDDT https://onlinelibrary.wiley.com/doi/abs/10.1002/jlcr.3516
• Pruxelutamide (GT-0918; proxalutamide) – androgen receptor antagonist for prostate cancer http://adisinsight.springer.com/drugs/800046361^[2]
• Pyrilutamide (KX-826) – androgen receptor antagonist for topical treatment of androgen-dependent scalp hair loss and acne^[3]
• Spironolactone (Aldactone) – androgen receptor antagonist for systemic treatment of acnehttps://www.isrctn.com/ISRCTN12892056^[4] https://www.clinicaltrials.gov/ct2/show/NCT03334682^[5] https://www.clinicaltrials.gov/ct2/show/NCT04582383

Atypical androgen receptor antagonists

• Dimethylcurcumin (ASC-J9) – androgen receptor degradation enhancer for topical acne treatment http://adisinsight.springer.com/drugs/800028542
• EPI-7386 – N-terminal domain androgen receptor antagonist for prostate cancer https://adisinsight.springer.com/drugs/800037973 https://www.essapharma.com/wp-content/uploads/2019/02/Final-Poster-Next-Gen_201902014_Website.pdf synthesis inhibitors
  • Seviteronel
  ] (VT-464) – CYP17A1 inhibitor (androgen synthesis inhibitor) for prostate cancer and breast cancer http://adisinsight.springer.com/drugs/800035241

Estrogenics

Estrogen receptor agonists

• EC508 – oral prodrug of estradiol (estrogen) with improved pharmacokinetics^{[6] [7] [8]}
• Erteberel (LY-500307, SERBA-1) – selective ERβ agonist for schizophrenia http://adisinsight.springer.com/drugs/800031986
• Estetrol (Donesta) – estrogen for menopausal symptoms and other indications http://adisinsight.springer.com/drugs/800044874

Selective estrogen receptor modulators

• Acolbifene (EM-652, SCH-57068) – selective estrogen receptor modulator for breast cancer http://adisinsight.springer.com/drugs/800013630
• Afimoxifene (4-hydroxytamoxifen; 4-OHT; TamoGel) – selective estrogen receptor modulator for topical treatment of breast cancer and hyperplasia http://adisinsight.springer.com/drugs/800019175
• Amcenestrant (SAR-439859; SERD '859) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer https://adisinsight.springer.com/drugs/800048980
• Camizestrant (AZ14066724, AZD-9833) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer https://adisinsight.springer.com/drugs/800052720
• Endoxifen (4-hydroxy-N-desmethyltamoxifen) – selective estrogen receptor modulator for breast cancer http://adisinsight.springer.com/drugs/800036114
• Giredestrant (GDC-9545; RG-6171) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer https://adisinsight.springer.com/drugs/800050643
• Imlunestrant (LY-3484356) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer and endometrial cancer https://adisinsight.springer.com/drugs/800056808
• Rintodestrant (G1T-48) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer https://adisinsight.springer.com/drugs/800052167

Estrogen receptor antagonists

• Fulvestrant-3 boronic acid (ZB716) – estrogen receptor antagonist (antiestrogen) for breast cancer^{[9] [10]}

Estrogen synthesis inhibitors

• Estradiol sulfamate (E2MATE, J995, PGL-2, PGL-2001, ZK-190628) – steroid sulfatase inhibitor (estrogen "activation" inhibitor) for endometriosis http://adisinsight.springer.com/drugs/800026648
• Leflutrozole (BGS-649) – aromatase inhibitor (estrogen synthesis inhibitor) for male hypogonadism http://adisinsight.springer.com/drugs/800032111

Progestogenics

Progesterone receptor agonists

• Hydroxyprogesterone caproate (LPCN-1107) – oral progesterone receptor agonist (progestogen/progestin) for prevention of preterm labor^[11]
• VOLT-02 – water-soluble conjugate of progesterone and neurosteroid for traumatic brain injury and gynecological disorders https://adisinsight.springer.com/drugs/800041522

Selective progesterone receptor modulators

• Telapristone (CDB-4124, Proellex, Proellex-V, Progenta) – selective progesterone receptor modulator for breast cancer, endometriosis, and uterine fibroids http://adisinsight.springer.com/drugs/800014404
• Vilaprisan (BAY-1002670) – selective progesterone receptor modulator for endometriosis and uterine fibroids http://adisinsight.springer.com/drugs/800033040

Progesterone receptor antagonists

• Onapristone (AR-18, IVV-1001, ZK-299, ZK-98299) – progesterone receptor antagonist (antiprogestogen) for prostate cancer http://adisinsight.springer.com/drugs/800000877

GnRH/gonadotropins

Kisspeptin receptor agonists

• MVT-602 (RVT-602, TAK-448) – small-molecule kisspeptin receptor agonist for female infertility and hypogonadism https://adisinsight.springer.com/drugs/800029425

Neurokinin/tachykinin receptor antagonists

• Elinzanetant (BAY-3427080; GSK-1144814; NT-814) – small-molecule NK₁ receptor and NK₃ receptor antagonist for hot flashes and "sex hormone disorders"https://adisinsight.springer.com/drugs/800044912

Mixed/combinations

Androgen and progesterone receptor modulators

• 11β-Methyl-19-nortestosterone dodecylcarbonate (CDB-4754) – dual androgen/anabolic steroid and progestin for use as a male birth control pill^[12]
• Dimethandrolone undecanoate (CDB-4521) – dual androgen/anabolic steroid and progestin for use as a male birth control pill^[13]

Androgen and estrogen receptor modulators

• Acolbifene/prasterone (Femivia) – selective estrogen receptor modulator and dehydroepiandrosterone supplement for hot flashes http://adisinsight.springer.com/drugs/800043933

Androgen, estrogen, and progesterone receptor modulators

• Ethinylestradiol/drospirenone/prasterone – estrogen, progestogen, and dehydroepiandrosterone combination for female birth control https://adisinsight.springer.com/drugs/800026485

See also

• List of investigational drugs

External links

• AdisInsight - Springer
• 2011 Medicines in Development for Women - PhRMA

Notes and References

1. Zeng S, Huang W, Zheng X, Liyan C, Zhang Z, Wang J, Shen Z . Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges . Eur J Med Chem . 210 . 112981 . January 2021 . 33160761 . 10.1016/j.ejmech.2020.112981 . 226287993 .
2. Tong. Youzhi. Chen. Chunyun. Wu. Juan. Yang. Jiangtao. Zhang. Huihui. Wu. Xiaojun. Duan. Yanmei. Gao. Wei. Qian. Weidong. Niu. Xiaoxia. Mi. Lili. Guo. Chuangxing. Abstract 614: Proxalutamide (GT0918), a potent androgen receptor pathway inhibitor. Cancer Research. 74. 19 Supplement. 2014. 614. 0008-5472. 10.1158/1538-7445.AM2014-614.
3. Web site: Pyrilutamide - Suzhou Kintor Pharmaceuticals . AdisInsight . Springer Nature Switzerland AG.
4. Renz S, Chinnery F, Stuart B, Day L, Muller I, Soulsby I, Nuttall J, Thomas K, Thomas KS, Sach T, Stanton L, Ridd MJ, Francis N, Little P, Eminton Z, Griffiths G, Layton AM, Santer M . Spironolactone for adult female acne (SAFA): protocol for a double-blind, placebo-controlled, phase III randomised study of spironolactone as systemic therapy for acne in adult women . BMJ Open . 11 . 8 . e053876 . August 2021 . 34446504 . 10.1136/bmjopen-2021-053876 . 8395279 .
5. Poinas A, Lemoigne M, Le Naour S, Nguyen JM, Schirr-Bonnans S, Riche VP, Vrignaud F, Machet L, Claudel JP, Leccia MT, Hainaut E, Beneton N, Dert C, Boisrobert A, Flet L, Chiffoleau A, Corvec S, Khammari A, Dréno B . FASCE, the benefit of spironolactone for treating acne in women: study protocol for a randomized double-blind trial . Trials . 21 . 1 . 571 . June 2020 . 32586344 . 7318446 . 10.1186/s13063-020-04432-w . free .
6. Web site: R&D Research . www.evestra.com . dead . https://web.archive.org/web/20170929164030/http://www.evestra.com/index-Dateien/Page1242.htm . 2017-09-29.
7. Elger W, Wyrwa R, Ahmed G, Meece F, Nair HB, Santhamma B, Killeen Z, Schneider B, Meister R, Schubert H, Nickisch K . Estradiol prodrugs (EP) for efficient oral estrogen treatment and abolished effects on estrogen modulated liver functions . J. Steroid Biochem. Mol. Biol. . 165 . Pt B . 305–311 . January 2017 . 27449818 . 10.1016/j.jsbmb.2016.07.008 . 26650319 .
8. Ahmed G, Elger W, Meece F, Nair HB, Schneider B, Wyrwa R, Nickisch K . A prodrug design for improved oral absorption and reduced hepatic interaction . Bioorg. Med. Chem. . 25 . 20 . 5569–5575 . October 2017 . 28886996 . 10.1016/j.bmc.2017.08.027 .
9. Liu J, Zheng S, Akerstrom VL, Yuan C, Ma Y, Zhong Q, Zhang C, Zhang Q, Guo S, Ma P, Skripnikova EV, Bratton MR, Pannuti A, Miele L, Wiese TE, Wang G . Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD) . J. Med. Chem. . 59 . 17 . 8134–40 . 2016 . 27529700 . 10.1021/acs.jmedchem.6b00753 . 5499704 .
10. Wang. G. Liu. J. Zheng. S. Miele. L. Wiese. T. Zhong. Q. Guo. S. Abstract P2-08-11: An orally bioavailable selective estrogen receptor downregulator. Cancer Research. 77. 4 Supplement. 2017. P2-08-11–P2-08-11. 0008-5472. 10.1158/1538-7445.SABCS16-P2-08-11.
11. Web site: Hydroxyprogesterone - Lipocine - AdisInsight .
12. Web site: Second potential male birth control pill passes human safety tests .
13. Web site: Dimethandrolone undecanoate shows promise as a male birth control pill .