Synthesis and Biological Evaluation of Second-Generation Tropanol-Based Androgen Receptor Modulators

Henrik Sunden; Mareike C. Holland; Pekka K. Poutiainen; Tiina Jaaskelainen; Juha T. Pulkkinen; Jorma J. Palvimo; Roger Olsson

doi:10.1021/jm501995n

Synthesis and Biological Evaluation of Second-Generation Tropanol-Based Androgen Receptor Modulators

Henrik Sunden, Mareike C. Holland, Pekka K. Poutiainen, Tiina Jaaskelainen, Juha T. Pulkkinen, Jorma J. Palvimo, Roger Olsson

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

To circumvent antiandrogen resistance in prostate cancer, antiandrogens effective for both the androgen receptor (AR) and AR mutants are required. The AR antagonists in this study originate from previous findings, which showed that subtle differences in substitution pattern lead to a conformational change that alters the ligand activity, rendering an agonist to an antagonist. We have identified small yet potent tropanol-based ligands possessing significant antiandrogenic activity with both wild-type AR and the two most common AR ligand binding domain (LBD) mutants.

Originalspråk	engelska
Sidor (från-till)	1569-1574
Tidskrift	Journal of Medicinal Chemistry
Volym	58
Nummer	3
DOI	https://doi.org/10.1021/jm501995n
Status	Published - 2015

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10.1021/jm501995n

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title = "Synthesis and Biological Evaluation of Second-Generation Tropanol-Based Androgen Receptor Modulators",

abstract = "To circumvent antiandrogen resistance in prostate cancer, antiandrogens effective for both the androgen receptor (AR) and AR mutants are required. The AR antagonists in this study originate from previous findings, which showed that subtle differences in substitution pattern lead to a conformational change that alters the ligand activity, rendering an agonist to an antagonist. We have identified small yet potent tropanol-based ligands possessing significant antiandrogenic activity with both wild-type AR and the two most common AR ligand binding domain (LBD) mutants.",

author = "Henrik Sunden and Holland, {Mareike C.} and Poutiainen, {Pekka K.} and Tiina Jaaskelainen and Pulkkinen, {Juha T.} and Palvimo, {Jorma J.} and Roger Olsson",

year = "2015",

doi = "10.1021/jm501995n",

language = "English",

volume = "58",

pages = "1569--1574",

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AU - Sunden, Henrik

AU - Holland, Mareike C.

AU - Poutiainen, Pekka K.

AU - Jaaskelainen, Tiina

AU - Pulkkinen, Juha T.

AU - Palvimo, Jorma J.

AU - Olsson, Roger

PY - 2015

Y1 - 2015

N2 - To circumvent antiandrogen resistance in prostate cancer, antiandrogens effective for both the androgen receptor (AR) and AR mutants are required. The AR antagonists in this study originate from previous findings, which showed that subtle differences in substitution pattern lead to a conformational change that alters the ligand activity, rendering an agonist to an antagonist. We have identified small yet potent tropanol-based ligands possessing significant antiandrogenic activity with both wild-type AR and the two most common AR ligand binding domain (LBD) mutants.

AB - To circumvent antiandrogen resistance in prostate cancer, antiandrogens effective for both the androgen receptor (AR) and AR mutants are required. The AR antagonists in this study originate from previous findings, which showed that subtle differences in substitution pattern lead to a conformational change that alters the ligand activity, rendering an agonist to an antagonist. We have identified small yet potent tropanol-based ligands possessing significant antiandrogenic activity with both wild-type AR and the two most common AR ligand binding domain (LBD) mutants.

U2 - 10.1021/jm501995n

DO - 10.1021/jm501995n

M3 - Article

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SN - 1520-4804

VL - 58

SP - 1569

EP - 1574

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 3

ER -

Synthesis and Biological Evaluation of Second-Generation Tropanol-Based Androgen Receptor Modulators

Sammanfattning

Ämnesklassifikation (UKÄ)

FN:s Globala mål

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