FLAG-003 for GBM and DIPG

AG488 as a therapy against gliomas
Ziegler et al. Oncotarget, 8(42):71833-71844, May 2017

The design and discovery of water soluble 4-substituted-2,6-dimethylfuro[2,3-d]pyrimidines as
multitargeted receptor tyrosine kinase inhibitors and microtubule targeting antitumor agents
Zhang et al. Bioorg Med Chem, 22(14):3753-72, July 2014

Diffuse intrinsic pontine glioma: current insights and future directions.
Srikanthan et al. Chin Neurosurg J, 7(1):6, January 2021

FLAG-094 for Mesothelioma

Therapeutic targeting malignant mesothelioma with a novel 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate via its selective uptake by the proton-coupled folate transporter.
Cherian et al. Cancer Chemother Pharmacol, 71(4):999-1011, April 2013

Structural and Enzymatic Analysis of Tumor-Targeted Antifolates That Inhibit Glycinamide Ribonucleotide Formyltransferase.
Deis et al. Biochemistry, 55(32):4574-82, August 2016

FLAG-094 for Ovarian Cancer

Dual Targeting of Epithelial Ovarian Cancer Via Folate Receptor α and the Proton-Coupled Folate Transporter with 6-Substituted Pyrrolo[2,3-d]pyrimidine Antifolates.
Hou et al. Mol Cancer Ther, 16(5):819-830, May 2017

Targeted therapy of pyrrolo[2,3-d]pyrimidine antifolates in a syngeneic mouse model of high grade serous ovarian cancer and the impact on the tumor microenvironment.
Wallace-Povirk et al. Sci Rep, 2(1):11346, July 2022

Pancreatic Cancer

Cellular Pharmacodynamics of a Novel Pyrrolo[3,2-d]pyrimidine Inhibitor Targeting Mitochondrial and Cytosolic One-Carbon Metabolism.
Dekhne et al. Mol Pharmacol, 97(1):9-22, January 2020

Novel Pyrrolo[3,2-d]pyrimidine Compounds Target Mitochondrial and Cytosolic One-carbon Metabolism with Broad-spectrum Antitumor Efficacy.
Dekhne et al. Mol Cancer Ther, 18(10):1787-1799, October 2019

SHMT2

A Review of Small-Molecule Inhibitors of One-Carbon Enzymes: SHMT2 and MTHFD2 in the Spotlight.
Cuthbertson et al. ACS Pharmacol Transl Sci, 4(2):624-646, March 2021

Therapeutic Targeting of Mitochondrial One-Carbon Metabolism in Cancer.
Dekhne et al. Mol Cancer Ther, 19(11):2245-2255, November 2020

Human SHMT inhibitors reveal defective glycine import as a targetable metabolic vulnerability of diffuse large B-cell lymphoma
Ducker et al. Proc Natl Acad Sci, 114(43):11404-11409, October 2017