Bicalutamide: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Alexander Berchansky

@@ Line 1: / Line 1: @@
 <StructureSection load='' size='340' side='right' caption='Caption for this structure' scene='10/1022391/Cv/2'>
-Bicalutamide, marketed as Casodex <ref name="ARA prostate">PMID: 24639562</ref><ref name="nonsteroidal">PMID: 16841196</ref>, is one of the most stable and tolerated Androgen receptor antagonist (ARA) used in the treatment of prostate cancer <ref name="ARA prostate" /><ref name="bicalutamide">PMID: 15833816</ref><ref name="AAWS">PMID: 28971898</ref>, belonging to the first generation of antiandrogens developed <ref name="ARA prostate" /><ref name="MoA">PMID: 35245614</ref>.
+Bicalutamide, marketed as Casodex <ref name="ARA prostate">PMID: 24639562</ref><ref name="nonsteroidal">PMID: 16841196</ref>, is one of the most stable and tolerated Androgen receptor (AR) antagonists (ARA) used in the treatment of prostate cancer <ref name="ARA prostate" /><ref name="bicalutamide">PMID: 15833816</ref><ref name="AAWS">PMID: 28971898</ref>, belonging to the first generation of antiandrogens developed <ref name="ARA prostate" /><ref name="MoA">PMID: 35245614</ref>.
-It is a competitive antagonist <ref name="Bicalutamide functions">PMID: 12015321</ref><ref name="MoA" /><ref name="AAWS" /> which binds to the LBD producing a transcriptionally inactive AR <ref name="Bicalutamide functions" />. However, it seems that the long-term use of these drugs and other first generation antiandrogens lead to withdrawal syndrome in prostate cancer resistant to castration patients <ref name="ARA prostate" /><ref name="nonsteroidal" />. In many cases, associated AR mutations, like W741L, can switch the mechanism of action of the drug from antagonist to agonist or partial agonist <ref name="ARA prostate" /><ref name="bicalutamide" /><ref name="nonsteroidal" /><ref name="Unexpected">PMID: 21506597</ref><ref name="MoA">PMID: 35245614</ref>.
+It is a competitive antagonist <ref name="Bicalutamide functions">PMID: 12015321</ref><ref name="MoA" /><ref name="AAWS" /> which binds to the Ligand-binding Domain (LBD) producing a transcriptionally inactive AR <ref name="Bicalutamide functions" />. However, it seems that the long-term use of these drugs and other first generation antiandrogens lead to withdrawal syndrome in prostate cancer resistant to castration patients <ref name="ARA prostate" /><ref name="nonsteroidal" />. In many cases, associated AR mutations, like W741L, can switch the mechanism of action of the drug from antagonist to agonist or partial agonist <ref name="ARA prostate" /><ref name="bicalutamide" /><ref name="nonsteroidal" /><ref name="Unexpected">PMID: 21506597</ref><ref name="MoA">PMID: 35245614</ref>.
 <scene name='10/1022391/Cv/4'>Androgen Receptor Ligand-binding Domain W741L Mutant Complex with R-bicalutamide</scene> ([[1z95]]).
@@ Line 16: / Line 16: @@
 For future research, it will be useful to understand the precise mechanism of action of antiandrogens currently used in the clinic, with the objective of developing new drugs which can escape from the antagonist-agonist switch seen in bicalutamide or flutamide. One example of this is apalutamide, a non-steroidal second generation antiandrogen <ref name="ARA prostate" /><ref name="Role of AR">PMID: 30209899</ref>, approved for use in non metastatic castration resistant prostate cancer patients by the FDA in 2018 <ref name="Role of AR" />. See also the [https://clinicaltrials.gov/ct2/show/NCT01946204 SPARTAN study]<ref>PMID: 29420164</ref>. This new drug has promising uses but it is still associated with side effects like an increased level of falls in patients with the treatment vs placebo <ref>PMID: 36209239</ref>.
-[[1z95]].
 </StructureSection>
 == References ==
 <references/>