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Small Molecule Kinase Inhibitors for the Treatment of Brain Cancer

Journal of medicinal chemistry, 2016-11, Vol.59 (22), p.10030-10066

Heffron, Timothy P

2016

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Prevalence of Acid-Reducing Agents (ARA) in Cancer Populations and ARA Drug–Drug Interaction Potential for Molecular Targeted Agents in Clinical Development

Molecular pharmaceutics, 2013-11, Vol.10 (11), p.4055-4062

2013

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Challenges of developing small-molecule kinase inhibitors for brain tumors and the need for emphasis on free drug levels

Neuro-oncology (Charlottesville, Va.), 2018-02, Vol.20 (3), p.307-312

Heffron, Timothy P

2018

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Noncovalent wild-type-sparing inhibitors of EGFR T790M

Cancer discovery, 2013-02, Vol.3 (2), p.168-181

2013

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Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor

Bioorganic & medicinal chemistry letters, 2010-04, Vol.20 (8), p.2408-2411

2010

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Ladder Polyether Synthesis via Epoxide-Opening Cascades Using a Disappearing Directing Group

Journal of the American Chemical Society, 2006-02, Vol.128 (4), p.1056-1057

2006

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SiMe3-Based Homologation−Epoxidation−Cyclization Strategy for Ladder THP Synthesis

Organic letters, 2003-06, Vol.5 (13), p.2339-2342

2003

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RTK-Dependent Inducible Degradation of Mutant PI3Kα Drives GDC-0077 (Inavolisib) Efficacy

Cancer discovery, 2022-01, Vol.12 (1), p.204-219

2022

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Discovery of 2‑{3-[2-(1-Isopropyl-3-methyl‑1H‑1,2–4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2‑d][1,4]oxazepin-9-yl]‑1H‑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 of medicinal chemistry, 2013-06, Vol.56 (11), p.4597-4610

2013

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Assessment of KRAS G12C Target Engagement by a Covalent Inhibitor in Tumor Biopsies Using an Ultra-Sensitive Immunoaffinity 2D-LC–MS/MS Approach

Analytical chemistry (Washington), 2022-09, Vol.94 (37), p.12927-12933

2022

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Hematopoietic Progenitor Kinase-1 Structure in a Domain-Swapped Dimer

Structure (London), 2019-01, Vol.27 (1), p.125-133.e4

2019

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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 of medicinal chemistry, 2016-02, Vol.59 (3), p.985-1002

2016

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Design of a brain-penetrant CDK4/6 inhibitor for glioblastoma

Bioorganic & medicinal chemistry letters, 2019-08, Vol.29 (16), p.2294-2301

2019

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Discovery of Clinical Development Candidate GDC-0084, a Brain Penetrant Inhibitor of PI3K and mTOR

ACS medicinal chemistry letters, 2016-04, Vol.7 (4), p.351-356

2016

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Noncovalent Mutant Selective Epidermal Growth Factor Receptor Inhibitors: A Lead Optimization Case Study

Journal of medicinal chemistry, 2015-11, Vol.58 (22), p.8877-8895

2015

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Brain Distribution and Efficacy of the Brain Penetrant PI3K Inhibitor GDC-0084 in Orthotopic Mouse Models of Human Glioblastoma

Drug metabolism and disposition, 2016-12, Vol.44 (12), p.1881-1889

2016

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4-Aminoindazolyl-dihydrofuro[3,4-d]pyrimidines as non-covalent inhibitors of mutant epidermal growth factor receptor tyrosine kinase

Bioorganic & medicinal chemistry letters, 2016-01, Vol.26 (2), p.534-539

2016

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Characterization of Antineovascularization Activity and Ocular Pharmacokinetics of Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitor GNE-947

Drug metabolism and disposition, 2020-05, Vol.48 (5), p.408-419

2020

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Discovery of Highly Potent, Selective, and Brain-Penetrable Leucine-Rich Repeat Kinase 2 (LRRK2) Small Molecule Inhibitors

Journal of medicinal chemistry, 2012-11, Vol.55 (22), p.9416-9433

2012

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Discovery of Selective and Noncovalent Diaminopyrimidine-Based Inhibitors of Epidermal Growth Factor Receptor Containing the T790M Resistance Mutation

Journal of medicinal chemistry, 2014-12, Vol.57 (23), p.10176-10191

2014

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Rational Design of Phosphoinositide 3-Kinase α Inhibitors That Exhibit Selectivity over the Phosphoinositide 3-Kinase β Isoform

Journal of medicinal chemistry, 2011-11, Vol.54 (22), p.7815-7833

2011

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Discovery of Spiro-azaindoline Inhibitors of Hematopoietic Progenitor Kinase 1 (HPK1)

ACS medicinal chemistry letters, 2022-01, Vol.13 (1), p.84-91

2022

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The Design and Identification of Brain Penetrant Inhibitors of Phosphoinositide 3‑Kinase α

Journal of medicinal chemistry, 2012-09, Vol.55 (18), p.8007-8020

2012

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Targeting the PI3K Pathway in the Brain-Efficacy of a PI3K Inhibitor Optimized to Cross the Blood―Brain Barrier

Clinical cancer research, 2012-11, Vol.18 (22), p.6239-6248

2012

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Small Molecule Kinase Inhibitors for the Treatment of Brain Cancer

Prevalence of Acid-Reducing Agents (ARA) in Cancer Populations and ARA Drug–Drug Interaction Potential for Molecular Targeted Agents in Clinical Development

Challenges of developing small-molecule kinase inhibitors for brain tumors and the need for emphasis on free drug levels

Noncovalent wild-type-sparing inhibitors of EGFR T790M

Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor

Ladder Polyether Synthesis via Epoxide-Opening Cascades Using a Disappearing Directing Group

SiMe3-Based Homologation−Epoxidation−Cyclization Strategy for Ladder THP Synthesis

RTK-Dependent Inducible Degradation of Mutant PI3Kα Drives GDC-0077 (Inavolisib) Efficacy

Discovery of 2‑{3-[2-(1-Isopropyl-3-methyl‑1H‑1,2–4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2‑d][1,4]oxazepin-9-yl]‑1H‑pyrazol-1-yl}-2-methylpropanamide (GDC-0032): A β‑Sparing Phosphoinositide 3‑Kinase Inhibitor with High Unbound Exposure and Robust in Vivo Antitumor Activity

Assessment of KRAS G12C Target Engagement by a Covalent Inhibitor in Tumor Biopsies Using an Ultra-Sensitive Immunoaffinity 2D-LC–MS/MS Approach

Hematopoietic Progenitor Kinase-1 Structure in a Domain-Swapped Dimer

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)

Design of a brain-penetrant CDK4/6 inhibitor for glioblastoma

Discovery of Highly Potent, Selective, and Brain-Penetrant Aminopyrazole Leucine-Rich Repeat Kinase 2 (LRRK2) Small Molecule Inhibitors

Discovery of Clinical Development Candidate GDC-0084, a Brain Penetrant Inhibitor of PI3K and mTOR

Noncovalent Mutant Selective Epidermal Growth Factor Receptor Inhibitors: A Lead Optimization Case Study

Brain Distribution and Efficacy of the Brain Penetrant PI3K Inhibitor GDC-0084 in Orthotopic Mouse Models of Human Glioblastoma

4-Aminoindazolyl-dihydrofuro[3,4-d]pyrimidines as non-covalent inhibitors of mutant epidermal growth factor receptor tyrosine kinase

Characterization of Antineovascularization Activity and Ocular Pharmacokinetics of Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitor GNE-947

Discovery of Highly Potent, Selective, and Brain-Penetrable Leucine-Rich Repeat Kinase 2 (LRRK2) Small Molecule Inhibitors

Discovery of Selective and Noncovalent Diaminopyrimidine-Based Inhibitors of Epidermal Growth Factor Receptor Containing the T790M Resistance Mutation

Rational Design of Phosphoinositide 3-Kinase α Inhibitors That Exhibit Selectivity over the Phosphoinositide 3-Kinase β Isoform

Discovery of Spiro-azaindoline Inhibitors of Hematopoietic Progenitor Kinase 1 (HPK1)

The Design and Identification of Brain Penetrant Inhibitors of Phosphoinositide 3‑Kinase α

Targeting the PI3K Pathway in the Brain-Efficacy of a PI3K Inhibitor Optimized to Cross the Blood―Brain Barrier

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