List of investigational sex-hormonal agents

This is a dynamic list and may never be able to satisfy particular standards for completeness. You can help by adding missing items with reliable sources.

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 It is likely to become outdated with time.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 ^{[1] [2]}

Selective androgen receptor modulators

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

Androgen receptor antagonists

• Bavdegalutamide (AVR-110) – androgen receptor antagonist for prostate cancer [3]
• Clascoterone (CB-03-01, Breezula, Winlevi) – androgen receptor antagonist for topical treatment of scalp hair loss
• Deutenzalutamide (deuterated enzalutamide; HC-1119) – androgen receptor antagonist for prostate cancer
• Pruxelutamide (GT-0918; proxalutamide) – androgen receptor antagonist for prostate cancer [4]
• Pyrilutamide (KX-826) – androgen receptor antagonist for topical treatment of androgen-dependent scalp hair loss and acne ^[5]
• Spironolactone (Aldactone) – androgen receptor antagonist for systemic treatment of acne [6] [7]

Atypical androgen receptor antagonists

• Dimethylcurcumin (ASC-J9) – androgen receptor degradation enhancer for topical acne treatment
• EPI-7386 – N-terminal domain androgen receptor antagonist for prostate cancer [https://www.prnewswire.com/news-releases/essa-pharma-announces-nomination-of-epi-7386-as-lead-clinical-candidate-in-metastatic-castration-resistant-prostate-cancer-300820449.html

Androgen synthesis inhibitors

• Seviteronel (VT-464) – CYP17A1 inhibitor (androgen synthesis inhibitor) for prostate cancer and breast cancer

Estrogenics

Estrogen receptor agonists

• EC508 – oral prodrug of estradiol (estrogen) with improved pharmacokinetics ^{[1] [8] [2]}
• Erteberel (LY-500307, SERBA-1) – selective ERβ agonist for schizophrenia
• Estetrol (Donesta) – estrogen for menopausal symptoms and other indications

Selective estrogen receptor modulators

• Acolbifene (EM-652, SCH-57068) – selective estrogen receptor modulator for breast cancer
• Afimoxifene (4-hydroxytamoxifen; 4-OHT; TamoGel) – selective estrogen receptor modulator for topical treatment of breast cancer and hyperplasia
• Amcenestrant (SAR-439859; SERD '859) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer
• Camizestrant (AZ14066724, AZD-9833) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer
• Endoxifen (4-hydroxy-N-desmethyltamoxifen) – selective estrogen receptor modulator for breast cancer
• Giredestrant (GDC-9545; RG-6171) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer
• Imlunestrant (LY-3484356) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer and endometrial cancer
• Rintodestrant (G1T-48) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer

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
• Leflutrozole (BGS-649) – aromatase inhibitor (estrogen synthesis inhibitor) for male hypogonadism

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

Selective progesterone receptor modulators

• Telapristone (CDB-4124, Proellex, Proellex-V, Progenta) – selective progesterone receptor modulator for breast cancer, endometriosis, and uterine fibroids
• Vilaprisan (BAY-1002670) – selective progesterone receptor modulator for endometriosis and uterine fibroids

Progesterone receptor antagonists

• Onapristone (AR-18, IVV-1001, ZK-299, ZK-98299) – progesterone receptor antagonist (antiprogestogen) for prostate cancer

GnRH/gonadotropins

GnRH receptor antagonists

• Merigolix (HS-10518, NCE-403, SKI-2670, TU-2670) – small-molecule GnRH antagonist for endometriosis and uterine fibroids

Kisspeptin receptor agonists

• MVT-602 (RVT-602, TAK-448) – small-molecule kisspeptin receptor agonist for female infertility and hypogonadism

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"

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

Androgen, estrogen, and progesterone receptor modulators

• Ethinylestradiol/drospirenone/prasterone – estrogen, progestogen, and dehydroepiandrosterone combination for female birth control

See also

• List of investigational drugs

References

1. "R&D Research". www.evestra.com. Archived from the original on 2017-09-29.
2. Ahmed G, Elger W, Meece F, Nair HB, Schneider B, Wyrwa R, Nickisch K (October 2017). "A prodrug design for improved oral absorption and reduced hepatic interaction". Bioorg. Med. Chem. 25 (20): 5569–5575. doi:10.1016/j.bmc.2017.08.027. PMID   28886996.
3. Zeng S, Huang W, Zheng X, Liyan C, Zhang Z, Wang J, Shen Z (January 2021). "Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges". Eur J Med Chem. 210: 112981. doi:10.1016/j.ejmech.2020.112981. PMID   33160761. S2CID   226287993.
4. Tong, Youzhi; Chen, Chunyun; Wu, Juan; Yang, Jiangtao; Zhang, Huihui; Wu, Xiaojun; Duan, Yanmei; Gao, Wei; Qian, Weidong; Niu, Xiaoxia; Mi, Lili; Guo, Chuangxing (2014). "Abstract 614: Proxalutamide (GT0918), a potent androgen receptor pathway inhibitor". Cancer Research. 74 (19 Supplement): 614. doi:10.1158/1538-7445.AM2014-614. ISSN   0008-5472.
5. "Pyrilutamide - Suzhou Kintor Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG.
6. 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 (August 2021). "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. doi:10.1136/bmjopen-2021-053876. PMC   8395279 . PMID   34446504.
7. 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 (June 2020). "FASCE, the benefit of spironolactone for treating acne in women: study protocol for a randomized double-blind trial". Trials. 21 (1): 571. doi: 10.1186/s13063-020-04432-w . PMC   7318446 . PMID   32586344.
8. Elger W, Wyrwa R, Ahmed G, Meece F, Nair HB, Santhamma B, Killeen Z, Schneider B, Meister R, Schubert H, Nickisch K (January 2017). "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. doi:10.1016/j.jsbmb.2016.07.008. PMID   27449818. S2CID   26650319.
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 (2016). "Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD)". J. Med. Chem. 59 (17): 8134–40. doi:10.1021/acs.jmedchem.6b00753. PMC   5499704 . PMID   27529700.
10. Wang, G; Liu, J; Zheng, S; Miele, L; Wiese, T; Zhong, Q; Guo, S (2017). "Abstract P2-08-11: An orally bioavailable selective estrogen receptor downregulator". Cancer Research. 77 (4 Supplement): P2-08-11–P2-08-11. doi:10.1158/1538-7445.SABCS16-P2-08-11. ISSN   0008-5472.
11. "Hydroxyprogesterone - Lipocine - AdisInsight".
12. "Second potential male birth control pill passes human safety tests".
13. "Dimethandrolone undecanoate shows promise as a male birth control pill".

External links

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