Reference Detail

Ref Type Journal Article
PMID (28978721)
Authors Venetsanakos E, Brameld KA, Phan VT, Verner E, Owens TD, Xing Y, Tam D, LaStant J, Leung K, Karr DE, Hill RJ, Gerritsen ME, Goldstein DM, Funk JO, Bradshaw JM
Title The Irreversible Covalent Fibroblast Growth Factor Receptor Inhibitor PRN1371 Exhibits Sustained Inhibition of FGFR after Drug Clearance.
Journal Molecular cancer therapeutics
Vol 16
Issue 12
Date 2017 Dec
URL
Abstract Text An increasing number of cancers are known to harbor mutations, translocations, or amplifications in the fibroblast growth factor receptor (FGFR) family of kinases. The FGFR inhibitors evaluated in clinical trials to date have shown promise at treating these cancers. Here, we describe PRN1371, an irreversible covalent inhibitor of FGFR1-4 targeting a cysteine within the kinase active site. PRN1371 demonstrated strong FGFR potency and excellent kinome-wide selectivity in a number of biochemical and cellular assays, including in various cancer cell lines exhibiting FGFR alterations. Furthermore, PRN1371 maintained FGFR inhibition in vivo, not only when circulating drug levels were high but also after the drug had been cleared from circulation, indicating the possibility of sustained FGFR inhibition in the clinic without the need for continuous drug exposure. Durable tumor regression was also obtained in multiple tumor xenografts and patient-derived tumor xenograft models and was sustained even using an intermittent dosing strategy that provided drug holidays. PRN1371 is currently under clinical investigation for treatment of patients with solid tumors. Mol Cancer Ther; 16(12); 2668-76. ©2017 AACR.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
FGFR2 - GAB2 fusion unknown FGFR2-GAB2 results from the fusion of FGFR2 and GAB2 (PMID: 28978721). FGFR2-GAB2 has been identified in breast cancer (PMID: 28978721) and esophageal adenocarcinoma (PMID: 28640357), but has not been biochemically characterized and therefore, the its effect on Fgfr2 protein function is unknown (PubMed, May 2019).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 K660N Advanced Solid Tumor sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation of transformed cells over expressing FGFR2 K660N in culture (PMID: 28978721). 28978721 detail...
FGFR3 over exp Advanced Solid Tumor sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation in transformed cells overexpressing wild-type FGFR3 in culture (PMID: 28978721). 28978721
FGFR2 amp FGFR2-COL14A1 colorectal adenocarcinoma sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation of colorectal adenocarcinoma cells harboring FGFR2 amplification and FGFR2-COL14A1 fusion in culture (PMID: 28978721). 28978721
FGFR1 amp lung adenocarcinoma sensitive PRN1371 Preclinical - Pdx Actionable In a preclinical study, PRN1371 treatment resulted in 64.6% tumor growth inhibition in patient-derived xenograft models of FGFR1-amplified lung adenocarcinoma (PMID: 28978721). 28978721
FGFR1 V561M Advanced Solid Tumor sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation of transformed cells over expressing FGFR1 V561M in culture (PMID: 28978721). 28978721
FGFR2 N550K Advanced Solid Tumor sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation of transformed cells over expressing FGFR2 N550K in culture (PMID: 28978721). 28978721
FGFR2-CCDC6 liver cancer sensitive PRN1371 Preclinical - Pdx Actionable In a preclinical study, PRN1371 treatment resulted in tumor regression in patient-derived xenograft models of liver cancer harboring FGFR2-CCDC6 fusion (PMID: 28978721). 28978721
FGFR3-TACC3 oligodendroglioma sensitive PRN1371 Preclinical - Pdx Actionable In a preclinical study, PRN1371 treatment resulted in tumor regression in patient-derived xenograft models of anaplastic oligodendroglioma harboring FGFR3-TACC3 fusion (PMID: 28978721). 28978721
FGFR3 K650M Advanced Solid Tumor sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation of transformed cells over expressing FGFR3 K650M in culture (PMID: 28978721). 28978721
FGFR2 K660E Advanced Solid Tumor sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation of transformed cells over expressing FGFR2 K660E in culture (PMID: 28978721). 28978721 detail...
FGFR1 over exp Advanced Solid Tumor sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation of transformed cells over expressing wild-type FGFR1 in culture (PMID: 28978721). 28978721
FGFR2 over exp Advanced Solid Tumor sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation of transformed cells over expressing wild-type FGFR2 in culture (PMID: 28978721). 28978721
FGFR3-TACC3 bladder urothelial carcinoma sensitive PRN1371 Preclinical - Cell line xenograft Actionable In a preclinical study, PRN1371 inhibited proliferation of bladder transitional cell carcinoma cell lines harboring FGFR3-TACC3 fusion in culture and tumor growth in cell line xenograft models (PMID: 28978721). 28978721
FGFR2 N549K endometrial adenocarcinoma sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation of endometrial adenocarcinoma cells harboring FGFR2 N549K in culture (PMID: 28978721). 28978721
FGFR2 amp non-small cell lung carcinoma sensitive PRN1371 Preclinical - Pdx Actionable In a preclinical study, PRN1371 treatment resulted in 67.5% tumor growth inhibition in patient-derived xenograft models of FGFR2-amplified non-small cell lung cancer (PMID: 28978721). 28978721
FGFR2 amp FGFR2-GAB2 breast cancer sensitive PRN1371 Preclinical - Pdx Actionable In a preclinical study, PRN1371 treatment resulted in 60.6% tumor growth inhibition in patient-derived xenograft models of breast cancer harboring FGFR2 amplification and FGFR2-GAB2 fusion (PMID: 28978721). 28978721
FGFR3 amp non-small cell lung carcinoma sensitive PRN1371 Preclinical - Pdx Actionable In a preclinical study, PRN1371 treatment resulted in 28.2% tumor growth inhibition in patient-derived xenograft models of FGFR3-amplified non-small cell lung cancer (PMID: 28978721). 28978721
FGFR2 amp stomach carcinoma sensitive PRN1371 Preclinical - Cell line xenograft Actionable In a preclinical study, PRN1371 inhibited proliferation of FGFR2 amplified gastric carcinoma cells in culture and tumor growth in cell line xenograft models (PMID: 28978721). 28978721
FGFR1 amp non-small cell lung carcinoma sensitive PRN1371 Preclinical - Pdx Actionable In a preclinical study, PRN1371 treatment resulted in 96.1% tumor growth inhibition in patient-derived xenograft models of FGFR1-amplified non-small cell lung cancer (PMID: 28978721). 28978721