ERK1 (Extracellular Signal-Regulated Kinase 1) and ERK2 belong to the MAP kinase family. ERK1 and ERK2 are the 2 ERKs which play an important role in the MAPK/ERK cascade. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements[2].
LY3214996 is a selective inhibitor of ERK1 and ERK2, with IC50 of 5 nM for both enzymes in biochemical assays. LY3214996 inhibits cellular phospho-RSK1 in BRAF and RAS mutant cancer cell lines. Anti-tumor activity of LY3214996 was observed in tumor cells with MAPK pathway alterations including BRAF, NRAS or KRAS mutation[1]. Another report suggested that LY3214996 may be effective against patient derived RAS-mutant NSCLC cell lines[3].
In tumor xenograft models, LY3214996 inhibits pharmadynamic biomarker phospho-p90RSK1 in tumors. LY3214996 shows either similar or superior anti-tumor activity as compared to other published ERK inhibitors in BRAF or RAS mutant cell lines and xenograft models. Oral administration of single-agent LY3214996 significantly inhibits tumor growth in vivo and is well tolerated in BRAF or NRAS mutant melanoma, BRAF or KRAS mutant colorectal, lung and pancreatic cancer xenografts or PDX models[1].
Temuterkib 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MDA-MB-468
0.1 nM–1 µM
over 10–14 days
To evaluate the synergistic effect with AKT inhibitor VIII, the combination of Temuterkib and Erlotinib showed potential weak synergy in the 468HR model
Biomedicines. 2023 Aug 28;11(9):2406.
NIH3T3 cells
5 μM
48 h
To study the inhibitory effect of Temuterkib on ERK1/2 and its impact on Per2 nucleocytoplasmic distribution
To evaluate the effect of ERK inhibitor LY3214996 on the growth of H/NRASQ61X mutant FN-RMS cells. The results showed that LY3214996 alone had limited effect on cell growth, but the combination with MEK inhibitor (e.g., trametinib) significantly inhibited ERK activity and induced cell cycle arrest, myogenic differentiation, and apoptosis
Mol Cancer Ther. 2022 Jan;21(1):170-183.
RD cells
100 nM
72 h
To evaluate the effect of ERK inhibitor LY3214996 on the growth of H/NRASQ61X mutant FN-RMS cells. The results showed that LY3214996 alone had limited effect on cell growth, but the combination with MEK inhibitor (e.g., trametinib) significantly inhibited ERK activity and induced cell cycle arrest, myogenic differentiation, and apoptosis
Mol Cancer Ther. 2022 Jan;21(1):170-183.
satellite cells
5 μM
24 h
To evaluate the effect of LY3214996 on satellite cell proliferation. The results showed that LY3214996 significantly reduced satellite cell proliferation, and this effect was more pronounced under CR
Cell Rep. 2024 Mar 26;43(3):113881.
Temuterkib 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
BA-induced cholemia model
Intracephalic injection
0.2 μM
Single injection
To study the reversal effect of Temuterkib on BA-induced circadian rhythm disorders
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