4.7 Article

Discovery of ARD-2051 as a Potent and Orally Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor for the Treatment of Advanced Prostate Cancer

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Review Oncology

Rational Second-Generation Antiandrogen Use in Prostate Cancer

Jacob J. Orme et al.

Summary: This report provides a comprehensive overview of the evidence and rational sequencing strategies for the use of second-generation antiandrogens in prostate cancer treatment. It highlights the growing list of approvals and indications for these drugs and suggests a prioritization sequence for their use in different stages of the disease. The report concludes that an optimized sequencing of second-generation antiandrogens with other treatment options is feasible based on current data.

ONCOLOGIST (2022)

Article Chemistry, Medicinal

Therapeutic Strategies to Target the Androgen Receptor

Weiguo Xiang et al.

Summary: The androgen receptor (AR) is crucial in maintaining muscle and bone, supporting male sexual functions, and progressing prostate cancer. Various AR-targeted therapies have been developed, including AR agonists for bone loss and muscle atrophy, and AR antagonists for prostate cancer treatment.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

Article Cell Biology

Chronologically modified androgen receptor in recurrent castration-resistant prostate cancer and its therapeutic targeting

Mithila Sawant et al.

Summary: Resistance to enzalutamide in castration-resistant prostate cancer (CRPC) is a common issue without effective therapeutic options. This study reveals that acetylation at Lys(609) in the DNA binding domain of androgen receptor (AR) allows AR translocation and confers enzalutamide insensitivity. The acetylation is mediated by ACK1 kinase-mediated AR Y267 phosphorylation, which leads to positive feedback loops at both transcriptional and posttranslational levels. Inhibiting ACK1 kinase with a small-molecule inhibitor compromises enzalutamide-resistant CRPC xenograft tumor growth.

SCIENCE TRANSLATIONAL MEDICINE (2022)

Review Chemistry, Multidisciplinary

Strategies for the discovery of oral PROTAC degraders aimed at cancer therapy

Xin Han et al.

Summary: This review focuses on the discovery and development of orally available anti-cancer PROTAC degraders, summarizing the strategies applied to this end, which may provide a reference for the future discovery of new oral-available PROTAC degraders for the treatment of various human diseases.

CELL REPORTS PHYSICAL SCIENCE (2022)

Article Chemistry, Medicinal

Are we ready to design oral PROTACs®?

Diego Garcia Jimenez et al.

Summary: The paper conducted a statistical study on the distribution of E3 ligases and POIs in PROTAC-DB, and focused on establishing a property-based design strategy for obtaining oral degraders. By comparing descriptors of publicly available degraders and orally approved drugs, a chemical space based on certain parameters was built to identify optimal permeability and bioavailability regions. Bioavailable degraders tended to be closer to the Ro5 region, while permeable degraders showed chameleonicity in their location within the chemical space.

ADMET AND DMPK (2021)

Article Multidisciplinary Sciences

Androgen receptor and its splice variant, AR-V7, differentially induce mRNA splicing in prostate cancer cells

Manjul Rana et al.

Summary: This study found differences in transcription and splicing regulation between AR-V7 and AR in prostate cancer, leading to the generation of different gene products.

SCIENTIFIC REPORTS (2021)

Article Medicine, General & Internal

Prostate cancer

Richard J. Rebello et al.

Summary: Prostate cancer is a prevalent disease among men, with key genetic alterations including gene fusions, oncogene amplification, and mutations in androgen receptors. Treatment options range from active surveillance to surgery and radiotherapy for localized disease.

NATURE REVIEWS DISEASE PRIMERS (2021)

Review Biochemistry & Molecular Biology

Undesirable Status of Prostate Cancer Cells after Intensive Inhibition of AR Signaling: Post-AR Era of CRPC Treatment

Tomoyuki Makino et al.

Summary: Recent research has highlighted the important role of the androgen receptor (AR) in prostate cancer, particularly in castration-resistant prostate cancer. While new AR signaling-targeted agents have been developed to inhibit AR activity, long-term use may lead to the emergence of AR-independent prostate cancer cells, which pose a challenge for effective treatment options. Further studies are needed to address the transformation mechanisms and potential treatment strategies for AR-independent prostate cancer.

BIOMEDICINES (2021)

Article Chemistry, Medicinal

Discovery of ARD-2585 as an Exceptionally Potent and Orally Active PROTAC Degrader of Androgen Receptor for the Treatment of Advanced Prostate Cancer

Weiguo Xiang et al.

Summary: This study identifies a promising AR degrader for the treatment of advanced prostate cancer, which demonstrates potent inhibition in cell lines with AR gene amplification or mutations and shows good oral bioavailability in mice.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Chemistry, Medicinal

Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer

Xin Han et al.

Summary: This study outlines strategies for discovering highly potent PROTAC degraders of androgen receptor (AR) with excellent oral pharmacokinetics, successfully identifying compound ARD-2128 as the most effective in inhibiting tumor growth in mice with good oral bioavailability.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Medicine, General & Internal

Causes of Death Among Patients With Metastatic Prostate Cancer in the US From 2000 to 2016

Ahmed O. Elmehrath et al.

Summary: This retrospective cohort study analyzed the causes of death among US patients with metastatic prostate cancer from 2000 to 2016. Noncancer causes, such as cardiovascular diseases, chronic obstructive pulmonary disease, and cerebrovascular diseases, were found to be significant contributors to mortality among these patients.

JAMA NETWORK OPEN (2021)

Article Multidisciplinary Sciences

Androgen receptor-binding sites are highly mutated in prostate cancer

Tunc Morova et al.

NATURE COMMUNICATIONS (2020)

Review Urology & Nephrology

Intermittent versus continuous androgen deprivation therapy for advanced prostate cancer

Marlon Perera et al.

NATURE REVIEWS UROLOGY (2020)

Review Oncology

Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations

E. David Crawford et al.

PROSTATE CANCER AND PROSTATIC DISEASES (2019)

Editorial Material Urology & Nephrology

Enzalutamide, apalutamide, or darolutamide: are apples or bananas best for patients?

Celestia Higano

NATURE REVIEWS UROLOGY (2019)

Review Pharmacology & Pharmacy

Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer

Zaina T. Al-Salama

Review Andrology

Role of Androgen Receptor in Prostate Cancer: A Review

Kazutoshi Fujita et al.

WORLD JOURNAL OF MENS HEALTH (2019)

Review Biotechnology & Applied Microbiology

Induced protein degradation: an emerging drug discovery paradigm

Ashton C. Lai et al.

NATURE REVIEWS DRUG DISCOVERY (2017)

Article Multidisciplinary Sciences

Lenalidomide induces ubiquitination and degradation of CK1a in del(5q) MDS

Jan Kroenke et al.

NATURE (2015)

Review Oncology

Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer

Philip A. Watson et al.

NATURE REVIEWS CANCER (2015)

Article Multidisciplinary Sciences

Identification of a Primary Target of Thalidomide Teratogenicity

Takumi Ito et al.

SCIENCE (2010)

Article Chemistry, Medicinal

Targeted intracellular protein degradation induced by a small molecule: En route to chemical proteomics

Ashley R. Schneekloth et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2008)

Article Multidisciplinary Sciences

Protacs: Chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation

KM Sakamoto et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2001)