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Novel small molecule guanidine Sigma1 inhibitors for advanced prostate cancer.

ABSTRACT: Prostate cancer is the most frequently diagnosed malignancy and the leading cause of cancer related death in men. First line therapy for disseminated disease relies on androgen deprivation, leveraging the addiction of these tumors on androgens for both growth and survival. Treatment typically involves antagonizing the androgen receptor (AR) or blocking the synthesis of androgens. Recurrence is common and within 2-3years patients develop castration resistant tumors that become unresponsive to AR-axis targeted therapies. In order to provide a more effective treatment, we are utilizing an approach that targets a key scaffolding protein, Sigma1 (also known as sigma-1 receptor), a unique 26-kilodalton integral membrane protein that is critical in stabilizing the AR. Herein we report on a new series of Sigma1 compounds for lead optimization derived from a hybrid pharmacophore approach.

SUBMITTER: Salvino JM

PROVIDER: S-EPMC5714280 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Novel small molecule guanidine Sigma1 inhibitors for advanced prostate cancer.

Salvino Joseph M JM Srikanth Yellamelli V V YVV Lou Rongliang R Oyer Halley M HM Chen Nan N Kim Felix J FJ

Bioorganic & medicinal chemistry letters 20170318 10

Prostate cancer is the most frequently diagnosed malignancy and the leading cause of cancer related death in men. First line therapy for disseminated disease relies on androgen deprivation, leveraging the addiction of these tumors on androgens for both growth and survival. Treatment typically involves antagonizing the androgen receptor (AR) or blocking the synthesis of androgens. Recurrence is common and within 2-3years patients develop castration resistant tumors that become unresponsive to AR- ...[more]

PMID: 28385503

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Dataset Information

Novel small molecule guanidine Sigma1 inhibitors for advanced prostate cancer.

Publications

Novel small molecule guanidine Sigma1 inhibitors for advanced prostate cancer.

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