| Identification | Back Directory | [Name]
Pyrazolo[1,5-a]pyrimidin-7(4H)-one, 5-(4-cyclohexylphenyl)-3-[[3-(fluoromethyl)-1-azetidinyl]carbonyl]-2-(3-methyl-2-pyrazinyl)- | [CAS]
2648450-42-2 | [Synonyms]
GNE-7883
5-(4-cyclohexylphenyl)-3-[[3-(fluoromethyl)-1-azetidinyl]carbonyl]-2-(3-methyl-2-pyrazinyl)-Pyrazolo[1,5-a]pyrimidin-7(4H)-one
Pyrazolo[1,5-a]pyrimidin-7(4H)-one, 5-(4-cyclohexylphenyl)-3-[[3-(fluoromethyl)-1-azetidinyl]carbonyl]-2-(3-methyl-2-pyrazinyl)- | [Molecular Formula]
C28H29FN6O2 | [MOL File]
2648450-42-2.mol | [Molecular Weight]
500.57 |
| Chemical Properties | Back Directory | [Boiling point ]
713.3±70.0 °C(Predicted) | [density ]
1.43±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
0.03±0.10(Predicted) | [color ]
White to light yellow |
| Hazard Information | Back Directory | [Uses]
GNE-7883 is a pan-TEAD inhibitor that blocks the association of YAP/TAZ with TEAD. GNE-7883 effectively reduces chromatin accessibility at TEAD motifs, inhibits cell proliferation in multiple cell line models, and achieves strong anti-tumor efficacy in vivo. In addition, GNE-7883 effectively overcomes intrinsic and acquired resistance to KRAS (Kirsten rat sarcoma viral oncogene homolog) G12C inhibitors in multiple preclinical models by inhibiting YAP/TAZ activation[1][2][3]. | [in vivo]
GNE-7883 (100 and 250 mg/kg; s.c.; once daily for 4 days) induces tumor growth arrest in NCI-H226 xenograft mice and tumor regression in MSTO-211H xenograft mice[1]. | Animal Model: | Mesothelioma NCIH226 xenograft mouse model[3] | | Dosage: | 250 mg/kg | | Administration: | Subcutaneous injection (s.c.); Once a day for 4 days | | Result: | Had a strong inhibitory effect on tumor growth in vivo, with an inhibition rate of 102%. |
| [IC 50]
YAP/TAZ-TEAD | [References]
[1] Hagenbeek TJ, et al. An allosteric pan-TEAD inhibitor blocks oncogenic YAP/TAZ signaling and overcomes KRAS G12C inhibitor resistance. Nat Cancer. 2023 Jun;4(6):812-828. DOI:10.1038/s43018-023-00577-0
[2] McGee L E. YAP Signaling Promotes Resistance to MEK Inhibition in NF1-Related MPNSTs[M]. Van Andel Research Institute, 2023.
[3] Barry E R, et al. Recent therapeutic approaches to modulate the Hippo pathway in oncology and regenerative medicine[J]. Cells, 2021, 10(10): 2715. DOI:10.3390/cells10102715 |
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