List of investigational sex-hormonal agents

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.

Androgenics

Androgen receptor agonists

EC586 – oral prodrug of testosterone (androgen/anabolic steroid) with improved pharmacokinetics^[1]^[2]

Androgen receptor antagonists

Bavdegalutamide (AVR-110) – androgen receptor antagonist for prostate cancer^[3][1]
Clascoterone (CB-03-01, Breezula, Winlevi) – androgen receptor antagonist for topical treatment of scalp hair loss [2]
Deuterated enzalutamide (HC-1119) – androgen receptor antagonist for prostate cancer [3] [4] [5]
Proxalutamide (GT-0918) – androgen receptor antagonist for prostate cancer [6]^[4]
Rezvilutamide (SHR3680) – androgen receptor antagonist for prostate cancer [7]
Spironolactone (Aldactone) – androgen receptor antagonist for systemic treatment of acne [8]^[5][9]^[6][10]

Atypical androgen receptor antagonists

Dimethylcurcumin (ASC-J9) – androgen receptor degradation enhancer for topical acne treatment [11]
EPI-7386 – N-terminal domain androgen receptor antagonist for prostate cancer [12] [13] [14]

Androgen synthesis inhibitors

Seviteronel (VT-464) – CYP17A1 inhibitor (androgen synthesis inhibitor) for prostate cancer and breast cancer [15]

Estrogenics

Estrogen receptor agonists

EC508 – oral prodrug of estradiol (estrogen) with improved pharmacokinetics^[1]^[7]^[2]
Erteberel (LY-500307, SERBA-1) – selective ERβ agonist for schizophrenia [16]
Estetrol (Donesta) – estrogen for menopausal symptoms and other indications [17]

Selective estrogen receptor modulators

Acolbifene (EM-652, SCH-57068) – selective estrogen receptor modulator for breast cancer [18]
Afimoxifene (4-hydroxytamoxifen; 4-OHT; TamoGel) – selective estrogen receptor modulator for topical treatment of breast cancer and hyperplasia [19]
Amcenestrant (SAR-439859; SERD '859) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer [20]
Camizestrant (AZ14066724, AZD-9833) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer [21]
Elacestrant (RAD-1901, ER-306323) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer [22]
Endoxifen (4-hydroxy-N-desmethyltamoxifen) – selective estrogen receptor modulator for breast cancer [23]
Giredestrant (GDC-9545; RG-6171) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer [24]
Rintodestrant (G1T-48) – selective estrogen receptor modulator and selective estrogen receptor degrader for breast cancer [25]

Estrogen receptor antagonists

Fulvestrant-3 boronic acid (ZB716) – estrogen receptor antagonist (antiestrogen) for breast cancer^[8]^[9]

Estrogen synthesis inhibitors

Estradiol sulfamate (E2MATE, J995, PGL-2, PGL-2001, ZK-190628) – steroid sulfatase inhibitor (estrogen "activation" inhibitor) for endometriosis [26]
Leflutrozole (BGS-649) – aromatase inhibitor (estrogen synthesis inhibitor) for male hypogonadism [27]

Progestogenics

Progesterone receptor agonists

Hydroxyprogesterone caproate (LPCN-1107) – oral progesterone receptor agonist (progestogen/progestin) for prevention of preterm labor^[10]
VOLT-02 – water-soluble conjugate of progesterone and neurosteroid for traumatic brain injury and gynecological disorders [28]

Selective progesterone receptor modulators

Telapristone (CDB-4124, Proellex, Proellex-V, Progenta) – selective progesterone receptor modulator for breast cancer, endometriosis, and uterine fibroids [29]
Vilaprisan (BAY-1002670) – selective progesterone receptor modulator for endometriosis and uterine fibroids [30]

Progesterone receptor antagonists

Onapristone (AR-18, IVV-1001, ZK-299, ZK-98299) – progesterone receptor antagonist (antiprogestogen) for prostate cancer [31]

GnRH/gonadotropins

Gonadotropin-releasing hormone receptor antagonists

Linzagolix (KLH-2109, OBE-2109) – small-molecule GnRH receptor antagonist for uterine fibroids and endometriosis [32]

Kisspeptin receptor agonists

MVT-602 (RVT-602, TAK-448) – small-molecule kisspeptin receptor agonist for female infertility and hypogonadism [33]

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"[34]
Fezolinetant (ESN-364) – small-molecule NK₃ receptor antagonist for hot flashes, polycystic ovary syndrome, and uterine fibroids [35]

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^[11]
Dimethandrolone undecanoate (CDB-4521) – dual androgen/anabolic steroid and progestin for use as a male birth control pill^[12]

Androgen and estrogen receptor modulators

Acolbifene/prasterone (Femivia) – selective estrogen receptor modulator and dehydroepiandrosterone supplement for hot flashes [36]

Androgen, estrogen, and progesterone receptor modulators

Ethinylestradiol/drospirenone/prasterone – estrogen, progestogen, and dehydroepiandrosterone combination for female birth control [37]

References

^ ^a ^b http://www.evestra.com/index-Dateien/Page1242.htm ^{[dead link‍]}
^ ^a ^b 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.
^ 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.
^ 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.
^ 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.
^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ 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.
^ 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.
^ 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.
^ https://adisinsight.springer.com/drugs/800038483
^ https://www.endocrine.org/news-room/2019/endo-2019---second-potential-male-birth-control-pill-passes-human-safety-tests
^ https://www.endocrine.org/news-room/2018/dimethandrolone-undecanoate-shows-promise-as-a-male-birth-control-pill

External links

[Evestra-1] ttp://www.evestra.com/index-Dateien/Page1242.htm ^{[dead link‍]}

[pmid28886996-2] 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.

[pmid33160761-3] 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.

[TongChen2014-4] 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.

[pmid34446504-5] 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.

[pmid32586344-6] 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[pmid27449818-7] 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.

[pmid27529700-8] 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.

[WangLiu2017-9] 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.

[AdisInsight-10] ttps://adisinsight.springer.com/drugs/800038483

[EndocrineSociety2019-11] ttps://www.endocrine.org/news-room/2019/endo-2019---second-potential-male-birth-control-pill-passes-human-safety-tests

[EndocrineSociety2018-12] ttps://www.endocrine.org/news-room/2018/dimethandrolone-undecanoate-shows-promise-as-a-male-birth-control-pill

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