Discovery of Potent, Selective, and In Vivo Efficacious AKT Kinase Protein Degraders via Structure–Activity Relationship Studies

AKT degradation selectively inhibits the growth of PI3K/PTEN pathway mutant cancers with wild-type KRAS and BRAF by destabilizing Aurora kinase B

(2021) Jia Xu et al.   Cancer Discovery

Design, Synthesis, and Evaluation of Potent, Selective, and Bioavailable AKT Kinase Degraders

(2021) Xufen Yu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Potent and Selective Epidermal Growth Factor Receptor (EGFR) Bifunctional Small-Molecule Degraders

(2020) Meng Cheng et al.   JOURNAL OF MEDICINAL CHEMISTRY

Spotlight on AKT: Current Therapeutic Challenges

(2020) Ina Landel et al.   ACS Medicinal Chemistry Letters

Discovery of First-in-class Protein Arginine Methyltransferase 5 (PRMT5) Degraders

(2020) Yudao Shen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER)

(2019) Jiantao Hu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer

(2019) Xin Han et al.   JOURNAL OF MEDICINAL CHEMISTRY

Development of targeted protein degradation therapeutics

(2019) Philip P. Chamberlain et al.   Nature Chemical Biology

Distinct functions of AKT isoforms in breast cancer: a comprehensive review

(2019) Nico Hinz et al.   Cell Communication and Signaling

Targeting AKT for cancer therapy

(2019) Maryam Shariati et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Discovery of a First-in-Class Mitogen-Activated Protein Kinase Kinase 1/2 Degrader

(2019) Jieli Wei et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeted protein degradation: expanding the toolbox

(2019) Matthieu Schapira et al.   NATURE REVIEWS DRUG DISCOVERY

Proteolysis Targeting Chimeras (PROTACs) of Anaplastic Lymphoma Kinase (ALK)

(2018) Chengwei Zhang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Selective eradication of cancer displaying hyperactive Akt by exploiting the metabolic consequences of Akt activation

(2018) Veronique Nogueira et al.   eLife

The Akt pathway in oncology therapy and beyond (Review)

(2018) George Nitulescu et al.   INTERNATIONAL JOURNAL OF ONCOLOGY

Maximising the potential of AKT inhibitors as anti-cancer treatments

(2017) Jessica S. Brown et al.   PHARMACOLOGY & THERAPEUTICS

Small-Molecule PROTACS: New Approaches to Protein Degradation

(2016) Momar Toure et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The PI3K/AKT Pathway as a Target for Cancer Treatment

(2016) Ingrid A. Mayer et al.   Annual Review of Medicine

AKT in cancer: new molecular insights and advances in drug development

(2016) Prabhjot S. Mundi et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Discovery of 3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (ARQ 092): An Orally Bioavailable, Selective, and Potent Allosteric AKT Inhibitor

(2016) Jean-Marc Lapierre et al.   JOURNAL OF MEDICINAL CHEMISTRY

Induced protein degradation: an emerging drug discovery paradigm

(2016) Ashton C. Lai et al.   NATURE REVIEWS DRUG DISCOVERY

PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer

(2016) Kanak Raina et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition

(2016) Julianty Frost et al.   Nature Communications

Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use (Review)

(2015) GEORGE MIHAI NITULESCU et al.   INTERNATIONAL JOURNAL OF ONCOLOGY

Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS

(2015) Jan Krönke et al.   NATURE

Prime time for PROTACs

(2015) Raymond J Deshaies   Nature Chemical Biology

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

Structure-Guided Design and Optimization of Small Molecules Targeting the Protein–Protein Interaction between the von Hippel–Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities

(2014) Carles Galdeano et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeting Akt3 Signaling in Triple-Negative Breast Cancer

(2013) Y. R. Chin et al.   CANCER RESEARCH

Diverse Mechanisms of AKT Pathway Activation in Human Malignancy

(2013) Mitchell Cheung et al.   CURRENT CANCER DRUG TARGETS

Discovery of 4-Amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an Orally Bioavailable, Potent Inhibitor of Akt Kinases

(2013) Matt Addie et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery and Preclinical Pharmacology of a Selective ATP-Competitive Akt Inhibitor (GDC-0068) for the Treatment of Human Tumors

(2012) James F. Blake et al.   JOURNAL OF MEDICINAL CHEMISTRY

Akt2 and Akt3 play a pivotal role in malignant gliomas

(2011) H. Mure et al.   NEURO-ONCOLOGY

Knockdown of Akt isoforms by RNA silencing suppresses the growth of human prostate cancer cells in vitro and in vivo

(2010) Toyokazu Sasaki et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Akt inhibitors in clinical development for the treatment of cancer

(2010) Sumanta Kumar Pal et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

MK-2206, an Allosteric Akt Inhibitor, Enhances Antitumor Efficacy by Standard Chemotherapeutic Agents or Molecular Targeted Drugs In vitro and In vivo

(2010) H. Hirai et al.   MOLECULAR CANCER THERAPEUTICS

Targeting the PI3K signaling pathway in cancer

(2009) Kwok-Kin Wong et al.   CURRENT OPINION IN GENETICS & DEVELOPMENT

Inhibitor hijacking of Akt activation

(2009) Tatsuya Okuzumi et al.   Nature Chemical Biology

Phosphatidylinositol 3-Kinase Hyperactivation Results in Lapatinib Resistance that Is Reversed by the mTOR/Phosphatidylinositol 3-Kinase Inhibitor NVP-BEZ235

(2008) P. J.A. Eichhorn et al.   CANCER RESEARCH

Identification of 4-(2-(4-Amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a Novel Inhibitor of AKT Kinase

(2008) Dirk A. Heerding et al.   JOURNAL OF MEDICINAL CHEMISTRY