Proxalutamide

Proxalutamide (developmental code name GT-0918) 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 (Stock Code: 9939.HK) for the potential treatment of COVID-19, prostate cancer, and breast cancer.[1][2][3][4][5]

Proxalutamide
Clinical data
Other namesGT-0918
Routes of
administration		By mouth
Drug classNonsteroidal antiandrogen
ATC code
  • None
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC24H19F4N5O2S
Molar mass517.50 g·mol−1
3D model (JSmol)

Indications

COVID-19

Androgen induces the expression of ACE2 and TMPRSS2, two key proteins for SARS-CoV-2 cellular entry and infection, which could be inhibited by the blockage of AR signaling with AR antagonist GT-0918. [6]A double-blinded, randomized, prospective, investigational phase III study of Proxalutamide treatment for 262 non-hospitalized COVID-19 male patients (NCT04446429) was completed in Brazil in December 2020. The extended study of 168 female patients is ongoing. The study shows that Proxalutamide has significantly reduced rate of hospitalization. [4][5]

Prostate Cancer

It inhibits AR-mediated gene transcription more potently than bicalutamide (by ~5- to 10-fold) and enzalutamide (by 2- to 5-fold) and maintains silent antagonism in metastatic castration-resistant prostate cancer (mCRPC) cells.[2] It has also been found to downregulate the AR, which could further confer it greater efficacy against mCRPC compared to existing NSAAs.[2] Unlike enzalutamide, the drug showed low central nervous system distribution and no induction of seizures in animals.[2][3]

In China, as of January 2021, Proxalutamide’s treatment for mCRPC (monotherapy) is in phase III registrational trial and Proxalumide’s combination with Abiraterone for treatement of mCRPC is also in phase III registrational trial. In the United States, monotherapy for mCRPC is in phase II clinical trial.[7][8]

Other indications

Proxalutamide can be used for the treatment of AR+ breast cancer, which is in phase Ic clinical trial in China.[1][9]

See also

References
  1. "Proxalutamide - Suzhou Kintor Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG.
  2. Tong Y, Chen C, Wu J, Yang J, Zhang H, Wu X, et al. (2014). "Proxalutamide (GT0918), a potent androgen receptor pathway inhibitor". Cancer Research. 74 (19 Supplement): 614. doi:10.1158/1538-7445.AM2014-614. ISSN 0008-5472.
  3. Tong Y, Chen C, Wu J, Zhang H, Wu X, Duan Y, Gao W, Niu X, Ma L, Guo C (2014). "Discovery of potent androgen receptor antagonists for treating CRPC and AR+ breast cancer". Cancer Research. 73 (8 Supplement): 2460. doi:10.1158/1538-7445.AM2013-2460. ISSN 0008-5472.
  4. Applied Biology, Inc. (2020-12-29). "Anti-Androgen Treatment for COVID-19". Cite journal requires |journal= (help)
  5. "EQS-News: Kintor's Proxalutamide (GT0918) COVID-19 Clinical Trial Shows Positive Re-sults in Treatment of Male and Female". Bloomberg.com. 2021-01-11. Retrieved 2021-01-29.
  6. Wu, Siqi; Miao, Liyan; Zhou, Qianxiang; Gao, Chang; Liu, Jialin; Zhan, Qingyuan; Guo, Binbin; Li, Fang; Wang, Yirong; Xu, Hongyang; Yan, Honghua (2020-04-20). "Suppression of Androgen Receptor (AR)-ACE2/TMPRSS2 Axis by AR Antagonists May Be Therapeutically Beneficial for Male COVID-19 Patients". Rochester, NY. Cite journal requires |journal= (help)
  7. "Product Pipeline_Kintor Pharmaceutical Limited". en.kintor.com.cn. Retrieved 2021-01-29.
  8. Suzhou Kintor Pharmaceutical Inc, (2020-03-13). "An Extended/Phase 2, Multi-Center, Randomized, Open-Label Study to Evaluate the Safety and Tolerability of GT0918 in Subjects With Metastatic Castrate Resistant Prostate Cancer (mCRPC) Who Failed Either Abiraterone or Enzalutamide". Cite journal requires |journal= (help)CS1 maint: extra punctuation (link)
  9. "Safety, Tolerability, and Pharmacokinetics of Proxalutamide Therapy in Women With Metastatic Breast Cancer - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2021-01-29.
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