Reference Detail

Request Content

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@genomenon.com

Ref Type Abstract
PMID
Authors Susan S. Liu-Chen; Jufang Lin; Jingyu Hu; Yanchao Liu; Weibo Zhang; Zhixiong Zhang; Yan Ding; Jinqiu Liu; Kevin Chen; Shaojing Hu
Title Abstract 1965: 3HP-2827-high selective inhibitor of FGFR2, a best-in-class therapy for FGFR2-driven solid tumors
Journal Vol Issue Date Pages Journal Short Title
Cancer Research 84 6_supplement March 22 2024 1965 Cancer Res
URL https://aacrjournals.org/cancerres/article/84/6_Supplement/1965/738272
Abstract Text FDA-approved pan-FGFR inhibitors bring encouraging results in solid tumors. However, resistance mechanisms and side effect profiles may limit their clinical utility. We designed 3HP-2827, a highly selective and potent small molecule inhibitor of FGFR2, to treat solid tumors harboring FGFR2 alterations, including amplifications, mutations, and fusions to overcome these limitations. 3HP-2827 inhibits FGFR2 enzyme activity with more than 1623-fold selectivity over FGFR1 and FGFR3. 3HP-2827 inhibits cell proliferation with IC50 <10 nM and 30 nM in FGFR2 amplified and FGFR2-mutant cancer cell lines, respectively. 3HP-2827 demonstrates high kinome selectivity for FGFR2 against a panel of 485 human kinases, resulting in 90.1% inhibition of FGFR2, and no other kinases showed greater than 75% inhibition. 3HP-2827 leads only modest activity at 10 µM against PDE4D2 and LCK in 44 distinct common adverse drug reaction targets, supporting its high degree of safety. 3HP-2827 also demonstrates a dose-dependent inhibition of phosphorylation of FGFR2 and FGFR2 signaling pathway nodes, including ERK and AKT, in the FGFR2-dependent cancer cell line. In vivo, 3HP-2827 demonstrates potent antitumor activity in cell- and patient-derived xenograft mouse models, including FGFR2-amplified gastric cancer, FGFR2-mutant (N549K) endometrial cancer, FGFR2 fusion ICC and gastric cancers. Strikingly, 3HP-2827 demonstrates superior activity in patient-derived ICC and gastric cancer, cell-derived endometrial cancer (CDX) in tumor and pFGFR2 inhibitions. In the ICC PDX model, 3HP-2827 also induces the regression of pemigatinib-resistant tumors. 3HP-2827 is well tolerated in the toxicology studies, and no hyperphosphatemia or tissue mineralization is observed at 150 mg/kg/kg/day in rats and 120 mg/kg/day in dogs. The data support that 3HP-2827, a potential to be a best-in-class selective FGFR2 inhibitor, will be studying clinically at the beginning of 2024.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. 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 on a longer phrase with spaces (i.e. "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
3HP-2827 3HP-2827 4 1
Drug Name Trade Name Synonyms Drug Classes Drug Description
3HP-2827 3HP 2827|3HP2827 FGFR2 Inhibitor 24 3HP-2827 selectively inhibits FGFR2, potentially resulting in decreased cell proliferation and tumor growth (Cancer Res (2024) 84 (6_Supplement): 1965).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 N549K endometrial cancer predicted - sensitive 3HP-2827 Preclinical - Cell line xenograft Actionable In a preclinical study, 3HP-2827 treatment demonstrated antitumor activity in a cell line xenograft model of endometrial cancer harboring FGFR2 N549K (Cancer Res (2024) 84 (6_Supplement): 1965). detail...
FGFR2 fusion intrahepatic cholangiocarcinoma predicted - sensitive 3HP-2827 Preclinical - Pdx Actionable In a preclinical study, 3HP-2827 treatment demonstrated antitumor activity and induced tumor regression in a patient-derived xenograft (PDX) model of intrahepatic cholangiocarcinoma harboring an FGFR2 fusion (Cancer Res (2024) 84 (6_Supplement): 1965). detail...
FGFR2 amp stomach cancer predicted - sensitive 3HP-2827 Preclinical - Pdx Actionable In a preclinical study, 3HP-2827 treatment demonstrated antitumor activity in a patient-derived xenograft (PDX) model of gastric cancer with FGFR2 amplification (Cancer Res (2024) 84 (6_Supplement): 1965). detail...
FGFR2 fusion stomach cancer predicted - sensitive 3HP-2827 Preclinical - Pdx Actionable In a preclinical study, 3HP-2827 treatment demonstrated antitumor activity in a patient-derived xenograft (PDX) model of gastric cancer harboring an FGFR2 fusion (Cancer Res (2024) 84 (6_Supplement): 1965). detail...