Wikipedia

GTx-027

GTx-027 is a selective androgen receptor modulator (SARM) which was under development for or of potential interest in the treatment of breast cancer and stress urinary incontinence (SUI) but was never marketed.[2][3][1][4][5] It is taken by mouth.[1]

GTx-027
Clinical data
Other namesGTx027
Routes of
administration		Oral[1]
Drug classSelective androgen receptor modulator[1]
Identifiers
  • (2S)-N-(3-chloro-4-cyanophenyl)-3-(4-cyanophenoxy)-2-hydroxy-2-methylpropanamide
PubChem CID
Chemical and physical data
FormulaC18H14ClN3O3
Molar mass355.78 g·mol−1
3D model (JSmol)
  • C[C@](COC1=CC=C(C=C1)C#N)(C(=O)NC2=CC(=C(C=C2)C#N)Cl)O
  • InChI=1S/C18H14ClN3O3/c1-18(24,11-25-15-6-2-12(9-20)3-7-15)17(23)22-14-5-4-13(10-21)16(19)8-14/h2-8,24H,11H2,1H3,(H,22,23)/t18-/m0/s1
  • Key:IEGVUEFEHAFTNS-SFHVURJKSA-N

Description

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The drug is a nonsteroidal androgen receptor (AR) modulator with mixed agonistic (androgenic) and antagonistic (antiandrogenic) effects.[1][5] It has been found to reduce the growth of androgen receptor-expressing MDA-MB-231 breast cancer cells in vitro.[6][7] In addition, it has been found to increase pelvic floor muscle weight in ovariectomized female rodents.[1][8][4] The drug has been found to increase body weight, lean body mass, and muscle strength in animals as well.[9][10] In terms of chemical structure, GTx-027 is a nonsteroidal arylpropionamide SARM and is an analogue of enobosarm (ostarine; GTx-024).[1][4]

GTx-027 was first described in the scientific literature by 2013.[5][11] It is said to have either not passed preclinical research[1] or to have reached phase 1 clinical trials prior to the discontinuation of its development.[3] The drug was developed by GTx.[2][3]

References

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  1. ^ a b c d e f g h Christiansen AR, Lipshultz LI, Hotaling JM, Pastuszak AW (March 2020). "Selective androgen receptor modulators: the future of androgen therapy?". Translational Andrology and Urology. 9 (Suppl 2): S135–S148. doi:10.21037/tau.2019.11.02. PMC 7108998. PMID 32257854.
  2. ^ a b "Research programme: selective androgen receptor modulators". AdisInsight. Springer Nature Switzerland AG. 16 April 2020. Retrieved 22 October 2024.
  3. ^ a b c "Delving into the Latest Updates on GTx-027 with Synapse". Synapse. 13 October 2024. Retrieved 22 October 2024.
  4. ^ a b c Ponnusamy S, Sullivan RD, Thiyagarajan T, Tillmann H, Getzenberg RH, Narayanan R (March 2017). "Tissue Selective Androgen Receptor Modulators (SARMs) Increase Pelvic Floor Muscle Mass in Ovariectomized Mice". Journal of Cellular Biochemistry. 118 (3): 640–646. doi:10.1002/jcb.25751. PMID 27681158.
  5. ^ a b c Dalton JT, Narayanan R, Steiner MS (15 December 2013). "Abstract P5-09-21: Selective androgen receptor modulators (SARMs): Enobosarm as targeted therapy for the treatment of androgen receptor-positive breast cancer". Cancer Research. 73 (24_Supplement). American Association for Cancer Research (AACR): P5–09–21–P5–09–21. doi:10.1158/0008-5472.sabcs13-p5-09-21. ISSN 0008-5472.
  6. ^ Vasiliou SK, Diamandis EP (May 2019). "Androgen receptor: A promising therapeutic target in breast cancer". Critical Reviews in Clinical Laboratory Sciences. 56 (3): 200–223. doi:10.1080/10408363.2019.1575643. PMID 30821186.
  7. ^ Christopoulos PF, Vlachogiannis NI, Vogkou CT, Koutsilieris M (December 2017). "The Role of the Androgen Receptor Signaling in Breast Malignancies". Anticancer Research. 37 (12): 6533–6540. doi:10.21873/anticanres.12109. PMID 29187427.
  8. ^ Juneau AD, Gomelsky A (28 October 2019). "Pharmaceutical Options for Stress Urinary Incontinence". Current Bladder Dysfunction Reports. 14 (4). Springer Science and Business Media LLC: 357–364. doi:10.1007/s11884-019-00537-4. ISSN 1931-7212.
  9. ^ Ponnusamy S, Sullivan RD, You D, Zafar N, He Yang C, Thiyagarajan T, et al. (July 2017). "Androgen receptor agonists increase lean mass, improve cardiopulmonary functions and extend survival in preclinical models of Duchenne muscular dystrophy". Human Molecular Genetics. 26 (13): 2526–2540. doi:10.1093/hmg/ddx150. PMC 6251687. PMID 28453658. After 2 weeks, the body weights of the GTx-026-treated mice were greater than those of the vehicle-treated mice, with this difference increasing in magnitude throughout the duration of the study (62% in GTx-026-treated mice vs 31% in vehicle-treated mice; P < 0.001) (Fig. 2B). GTx-026 treatment also increased lean mass (20% vs 60%; P < 0.001) compared with vehicle treatment. Consistent with the increase in lean mass, grip strength also increased in the GTx-026-treated animals (Fig. 2B). These results were reproduced with the other two SARMs, GTx-024 and GTx-027, indicating that these effects are SARM-dependent (Supplementary Material, Fig. S1B).
  10. ^ "GTx, Inc. Announces Results From Preclinical Studies Of Sarms In Duchenne Muscular Dystrophy Models Published In Human Molecular Genetics". BioSpace. 3 May 2017. Retrieved 22 October 2024. Other SARMs in the Company's portfolio, GTx-024 (enobosarm) and GTx-027, showed similar positive effects on muscle mass, function, and histological characteristics.
  11. ^ Narayanan R, Ahn S, Cheney MD, Yepuru M, Miller DD, Steiner MS, et al. (2014). "Selective androgen receptor modulators (SARMs) negatively regulate triple-negative breast cancer growth and epithelial:mesenchymal stem cell signaling". PLOS ONE. 9 (7): e103202. Bibcode:2014PLoSO...9j3202N. doi:10.1371/journal.pone.0103202. PMC 4114483. PMID 25072326.
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