Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

Discovery of GDC-0077 (Inavolisib), a Highly Selective Inhibitor and Degrader of Mutant PI3Kα

Journal Article · · Journal of Medicinal Chemistry
 [1];  [1];  [2];  [2];  [1];  [1];  [1];  [1];  [2];  [1];  [1];  [1];  [3];  [1];  [2];  [1];  [2];  [1];  [2];  [1] more »;  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [3];  [2];  [1];  [1];  [1] « less
  1. Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States
  2. Early Discovery Charles River, 7/8 Spire Green Centre, Flex Meadow, Harlow, Essex CM19 5TR, U.K.
  3. Pharmaron Beijing Co., Ltd, No. 6 Taihe Road, BDA, Beijing 100176, P. R. China
+ Show Author Affiliations
Not provided.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC02-06CH11357
OSTI ID:
2423388
Journal Information:
Journal of Medicinal Chemistry, Journal Name: Journal of Medicinal Chemistry Journal Issue: 24 Vol. 65; ISSN 0022-2623
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English

References (51)

A Pharmacological Map of the PI3-K Family Defines a Role for p110α in Insulin Signaling journal May 2006
Small-Molecule Kinase Downregulators journal January 2018
Monomeric Targeted Protein Degraders journal April 2020
Profile of buparlisib and its potential in the treatment of breast cancer: evidence to date journal January 2018
PI3K and cancer: lessons, challenges and opportunities journal January 2014
Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer journal September 2018
The Phosphoinositide 3-Kinase Pathway journal May 2002
Abstract OT1-08-04: A first-in-human phase Ia dose escalation study of GDC-0077, a p110a-selective and mutant-degrading PI3K inhibitor, in patients with PIK3CA-mutant solid tumors journal February 2020
PIK3CA Mutations Correlate with Hormone Receptors, Node Metastasis, and ERBB2, and Are Mutually Exclusive with PTEN Loss in Human Breast Carcinoma journal April 2005
Oncogenic mutations mimic and enhance dynamic events in the natural activation of phosphoinositide 3-kinase p110α ( PIK3CA ) journal September 2012
Induced protein degradation: an emerging drug discovery paradigm journal November 2016
A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2− Metastatic Breast Cancer journal January 2017
Essential roles of PI(3)K–p110β in cell growth, metabolism and tumorigenesis journal June 2008
Critical role for the p110α phosphoinositide-3-OH kinase in growth and metabolic regulation journal April 2006
High Frequency of Mutations of the PIK3CA Gene in Human Cancers journal April 2004
Pictilisib PI3Kinase inhibitor (a phosphatidylinositol 3-kinase [PI3K] inhibitor) plus paclitaxel for the treatment of hormone receptor-positive, HER2-negative, locally recurrent, or metastatic breast cancer: interim analysis of the multicentre, placebo-controlled, phase II randomised PEGGY study journal November 2016
Abstract P1-19-46: A phase Ib dose escalation study evaluating the mutant selective PI3K-alpha inhibitor GDC-0077 (G) in combination with letrozole (L) with and without palbociclib (P) in patients with PIK3CA-mutant HR+/HER2- breast cancer journal February 2020
Targeting the phosphoinositide 3-kinase pathway in cancer journal August 2009
Mutant PIK3CA promotes cell growth and invasion of human cancer cells journal June 2005
Take your PIK: phosphatidylinositol 3-kinase inhibitors race through the clinic and toward cancer therapy journal January 2009
Discovery of 2-{3-[2-(1-Isopropyl-3-methyl-1 H -1,2–4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2- d ][1,4]oxazepin-9-yl]-1 H -pyrazol-1-yl}-2-methylpropanamide (GDC-0032): A β-Sparing Phosphoinositide 3-Kinase Inhibitor with High Unbound Exposure and Robust in Vivo Antitumor Activity journal June 2013
Suppression of Feedback Loops Mediated by PI3K/mTOR Induces Multiple Overactivation of Compensatory Pathways: An Unintended Consequence Leading to Drug Resistance journal November 2014
The Rational Design of Selective Benzoxazepin Inhibitors of the α-Isoform of Phosphoinositide 3-Kinase Culminating in the Identification of (S)-2-((2-(1-Isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)oxy)propanamide (GDC-0326) journal January 2016
The phosphatidylinositol 3-Kinase–AKT pathway in human cancer journal July 2002
The influence of drug-like concepts on decision-making in medicinal chemistry journal November 2007
Discovery and saturation analysis of cancer genes across 21 tumour types journal January 2014
Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial journal June 2016
Intramolecular OH⋅⋅⋅FC Hydrogen Bonding in Fluorinated Carbohydrates: CHF is a Better Hydrogen Bond Acceptor than CF2 journal August 2013
Phase III study of taselisib (GDC-0032) + fulvestrant (FULV) v FULV in patients (pts) with estrogen receptor (ER)-positive, PIK3CA-mutant (MUT), locally advanced or metastatic breast cancer (MBC): Primary analysis from SANDPIPER. journal June 2018
Management of adverse events associated with idelalisib treatment: expert panel opinion journal May 2015
Halogen acceptors in hydrogen bonding journal March 2006
Fluorine Bonding — How Does It Work In Protein−Ligand Interactions? journal September 2009
Phosphatidylinositol 3-Kinase α–Selective Inhibition With Alpelisib (BYL719) in PIK3CA -Altered Solid Tumors: Results From the First-in-Human Study journal May 2018
Protac-Induced Protein Degradation in Drug Discovery: Breaking the Rules or Just Making New Ones? journal December 2017
Synthesis of PI3K inhibitor GDC-0077 via a stereocontrolled N-arylation of α-amino acids journal August 2019
Fluorine in Medicinal Chemistry journal April 2004
PI3K in lymphocyte development, differentiation and activation journal April 2003
When poor solubility becomes an issue: From early stage to proof of concept journal August 2007
An Integrative Genomic and Proteomic Analysis of PIK3CA, PTEN, and AKT Mutations in Breast Cancer journal August 2008
FDA Approval: Idelalisib Monotherapy for the Treatment of Patients with Follicular Lymphoma and Small Lymphocytic Lymphoma journal February 2015
p110δ, a Novel Phosphatidylinositol 3-Kinase Catalytic Subunit That Associates with p85 and Is Expressed Predominantly in Leukocytes journal August 1997
A Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB) journal May 2019
Essential, Nonredundant Role for the Phosphoinositide 3-Kinase p110δ in Signaling by the B-Cell Receptor Complex journal December 2002
Metabolic Stability Screen for Drug Discovery Using Cassette Analysis and Column Switching journal January 2007
First-in-Human Phase I Study of Pictilisib (GDC-0941), a Potent Pan–Class I Phosphatidylinositol-3-Kinase (PI3K) Inhibitor, in Patients with Advanced Solid Tumors journal November 2014
LBA18 Overall survival (os) results from SOLAR-1, a phase III study of alpelisib (ALP) + fulvestrant (FUL) for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) journal September 2020
RTK-Dependent Inducible Degradation of Mutant PI3Kα Drives GDC-0077 (Inavolisib) Efficacy journal September 2021
Central Role for G Protein-Coupled Phosphoinositide 3-Kinase γ in Inflammation journal February 2000
Abstract CT109: A phase I/Ib study evaluating GDC-0077 plus fulvestrant in patients with PIK3CA-mutant, hormone receptor-positive/HER2-negative breast cancer journal August 2020
The Structural Basis of PI3K Cancer Mutations: From Mechanism to Therapy journal February 2014
Four‐Component Synthesis of Fully Substituted 1,2,4‐Triazoles journal December 2009

Similar Records

Discovery of Pyridopyrimidinones that Selectively Inhibit the H1047R PI3Kα Mutant Protein
Journal Article · 2024 · Journal of Medicinal Chemistry · OSTI ID:2470260
Discovery of AK-1690: A Potent and Highly Selective STAT6 PROTAC Degrader
Journal Article · 2024 · Journal of Medicinal Chemistry · OSTI ID:2581511
Discovery of MK-8189, a Highly Potent and Selective PDE10A Inhibitor for the Treatment of Schizophrenia
Journal Article · 2023 · Journal of Medicinal Chemistry · OSTI ID:2423389

Related Subjects

Pharmacology & Pharmacy