| Pharmaceutical Information |
| Drug Name |
Apalutamide |
| Drug ID |
BADD_D02490 |
| Description |
Apalutamide is a potent androgen receptor (AR) antagonist that selectively binds to the ligand-binding domain of AR and blocks AR nuclear translocation or binding to androgen response elements [A31846]. It has been used in trials studying the treatment of Prostate Cancer, Hepatic Impairment, Prostatic Neoplasms, Castration-Resistant Prostate Cancer, and Prostatic Neoplasms, Castration-Resistant, among others. Exerting an antitumor action, apalutamide blocking the effect of androgens that promote tumor growth. It targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets in prostate tumors [A31846]. In mice bearing human CRPC xenograft models, apalutamide treatment produced tumor regressions in a dose-dependent manner that was more effective than that of [DB01128] or [DB08899]. Unlike bicalutamide, apalutamide antagonized AR-mediated signaling in AR overexpressing human CRPC cell lines [A31846].
Androgen-deprivation therapy, or hormone therapy, can be used as part of maintenance therapy for patients with non-metastatic prostate cancer. Although most patients achieve therapeutic responses at the initial hormone therapy, many patients progress to non-metastatic castration-resistant (resistance to hormone therapy) prostate cancer which is the second-most common cause of cancer-related deaths in American males [A31852]. Castration-resistant prostate cancer is often incurable, which poses significant clinical challenges for patients. Approximately 10 to 20 % of prostate cancer cases are castration-resistant, and up to 16% of these patients show no evidence of cancer metastasis at the time of castration-resistant diagnosis [L1295]. Higher prostate-specific antigen (PSA) and shorter PSA doubling time (PSA DT) are associated with a higher risk for metastases and death [A31846]. In a phase-2 multicenter open-label study, 89% of patients with non-metastatic, castration-resistant prostate cancer had ≥50% PSA decline at week 12 of apalutamide treatment [A31846]. In a randomized trial, the median metastasis-free survival for patients taking apalutamide was 40.5 months compared to 16.2 months for patients taking a placebo [L1295]. Apalutamide displayed good tolerability and safety profile in clinical studies.
Apalutamide was approved in February 2018 by the FDA as Erleada for the treatment of patients with non-metastatic prostate cancer that is resistant to treatment with hormone therapy (castration-resistant). It is available as oral tablets. Apalutamide is the first FDA-approved treatment for non-metastatic, castration-resistant prostate cancer [L1295]. |
| Indications and Usage |
Indicated for the treatment of patients with non-metastatic, castration-resistant prostate cancer (NM-CRPC) [FDA Label]. |
| Marketing Status |
approved; investigational |
| ATC Code |
L02BB05 |
| DrugBank ID |
DB11901
|
| KEGG ID |
D11040
|
| MeSH ID |
C572045
|
| PubChem ID |
24872560
|
| TTD Drug ID |
D0S7LG
|
| NDC Product Code |
11014-0330; 59676-604; 59676-600; 68554-0127; 71796-033; 12578-621; 54893-0100; 71796-019; 65267-116; 11014-0485; 17314-215 |
| UNII |
4T36H88UA7
|
| Synonyms |
apalutamide | ARN-509 | Erleada |
|
| Chemical Information |
| Molecular Formula |
C21H15F4N5O2S |
| CAS Registry Number |
956104-40-8 |
| SMILES |
CNC(=O)C1=C(C=C(C=C1)N2C(=S)N(C(=O)C23CCC3)C4=CC(=C(N=C4)C#N)C(F)(F)F)F |
| Chemical Structure |
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| ADRs Induced by Drug |
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