GDC-0084

a novel and potent small-molecule PI3K-mTOR dual inhibitor

Also Known As:

2-Pyrimidinamine, 5-(8,9-dihydro-6,6-dimethyl-4-(4-morpholinyl)-6H-(1,4)oxazino(4,3-e)purin-2-yl)-; 5-(6,6-Dimethyl-4-(4-morpholinyl)-8,9-dihydro-6H-(1,4)oxazino(4,3-e)purin-2-yl)-2-pyrimidinamine

Networked: 7 relevant articles (2 outcomes, 4 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Heterocyclic Compounds: 198
- 1-Ring Heterocyclic Compounds
  - Pyrimidines: 510
    - GDC-0084: 7
  - Oxazines: 9
    - GDC-0084: 7

Experts

1.	Olivero, Alan G: 3 articles (01/2020 - 12/2016)
2.	Cloughesy, Timothy F: 2 articles (01/2020 - 01/2020)
3.	Ellingson, Benjamin M: 2 articles (01/2020 - 01/2020)
4.	Gerstner, Elizabeth: 2 articles (01/2020 - 01/2020)
5.	Mueller, Lars U: 2 articles (01/2020 - 01/2020)
6.	Rodon, Jordi: 2 articles (01/2020 - 01/2020)
7.	Wen, Patrick Y: 2 articles (01/2020 - 01/2020)
8.	Campagne, Olivia: 1 article (01/2020)
9.	Chakhoyan, Ararat: 1 article (01/2020)
10.	Coimbra, Alexandre F: 1 article (01/2020)

Related Diseases

1.	Breast Neoplasms (Breast Cancer) 01/01/2019 - " Design: The efficacy of GDC-0084 was evaluated in PIK3CA-mutant and PIK3CA wild-type breast cancer cell lines and the isogenic pairs of PIK3CA wild-type and mutant (H1047R/+) MCF10A cells in vitro. " 01/01/2019 - "The results of this study suggest that the brain-penetrant PI3K/mTOR targeting GDC-0084 is a promising treatment option for breast cancer brain metastases with dysregulated PI3K/mTOR signaling pathway conferred by activating PIK3CA mutations. " 01/01/2019 - "In vivo, the effect of GDC-0084 was investigated in breast cancer brain metastasis xenograft mouse models and assessed by bioluminescent imaging and IHC. " 01/01/2019 - "The Dual PI3K/mTOR Pathway Inhibitor GDC-0084 Achieves Antitumor Activity in PIK3CA-Mutant Breast Cancer Brain Metastases." 01/01/2019 - "In vitro, GDC-0084 considerably decreased cell viability, induced apoptosis, and inhibited phosphorylation of Akt and p70 S6 kinase in a dose-dependent manner in PIK3CA-mutant breast cancer brain metastatic cell lines. "
2.	Brain Neoplasms (Brain Tumor) 01/01/2020 - "FDG-PET and concentration data from brain tumor tissue suggest that GDC-0084 crossed the blood-brain barrier." 01/01/2019 - "In vivo, treatment with GDC-0084 markedly inhibited the growth of PIK3CA-mutant, with accompanying signaling changes, and not PIK3CA wild-type brain tumors. " 01/01/2019 - "The results of this study suggest that the brain-penetrant PI3K/mTOR targeting GDC-0084 is a promising treatment option for breast cancer brain metastases with dysregulated PI3K/mTOR signaling pathway conferred by activating PIK3CA mutations. " 01/01/2019 - "The Dual PI3K/mTOR Pathway Inhibitor GDC-0084 Achieves Antitumor Activity in PIK3CA-Mutant Breast Cancer Brain Metastases."
3.	Glioblastoma (Glioblastoma Multiforme) 12/01/2016 - "Brain Distribution and Efficacy of the Brain Penetrant PI3K Inhibitor GDC-0084 in Orthotopic Mouse Models of Human Glioblastoma." 01/01/2019 - "GDC-0084 is a brain penetrant, dual PI3K/mTOR inhibitor that has shown promising activity in a preclinical model of glioblastoma. "
4.	Glioma (Gliomas) 01/01/2020 - "Multiparametric advanced MR-PET imaging was performed to evaluate physiologic response in a first-in-man, multicenter, phase I, dose-escalation study of GDC-0084 (NCT01547546) in 47 patients with recurrent malignant glioma. " 01/01/2020 - "First-in-Human Phase I Study to Evaluate the Brain-Penetrant PI3K/mTOR Inhibitor GDC-0084 in Patients with Progressive or Recurrent High-Grade Glioma." 01/01/2020 - "This method was successfully applied to analyze serial plasma samples obtained from children with diffuse intrinsic pontine gliomas and other midline gliomas who participated in pharmacokinetic studies as part of a phase I clinical trial of GDC-0084." 01/01/2020 - "Multiparametric MR-PET Imaging Predicts Pharmacokinetics and Clinical Response to GDC-0084 in Patients with Recurrent High-Grade Glioma."
5.	Neoplasms (Cancer) 01/01/2020 - "In two resection specimens, GDC-0084 was detected at similar levels in tumor and brain tissue, with a brain tissue/tumor-to-plasma ratio of >1 and >0.5 for total and free drug, respectively. " 10/01/2018 - "In vivo, GDC-0084 daily gavage potently inhibited A431 xenograft tumor growth in mice. " 12/01/2016 - "GDC-0084 distribution throughout the brain and intracranial tumors led to potent inhibition of the PI3K pathway. " 12/01/2016 - "GDC-0084 achieved significant tumor growth inhibition of 70% and 40% against the U87 and GS2 orthotopic models, respectively. " 12/01/2016 - "MALDI imaging showed GDC-0084 distributed evenly in brain and intracranial U87 and GS2 tumors. "

Related Drugs and Biologics

1.	70-kDa Ribosomal Protein S6 Kinases (Ribosomal Protein S6 Kinases, 70 kDa)
2.	Member 1 Subfamily B ATP Binding Cassette Transporter
3.	Proteins (Proteins, Gene)
4.	Plicamycin
5.	Panobinostat
6.	14- methyl- 20- oxa- 5,7,14,26- tetraazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa- 1(25),2(26),3,5,8(27),9,11,16,21,23- decaene
7.	lestaurtinib

Related Therapies and Procedures

1.	Lasers (Laser)