MYC proteins, including MYC, MYCL, and MYCN, play critical roles in tumorigenesis and therapeutic resistance. MYCi361 is an inhibitor of MYC that binds to intracellular MYC with a KD of 3.2 μM. Treatment of PC3 cells with MYCi361 (4–10 μM; 0.5 hr) led to significant thermal destabilization of MYC protein. Treatment of PC3 cells with MYCi361 (6 μM; 1 hr) led to disruption of the MYC/MAX interaction. MYCi361 (6 μM) decreased MYC protein stability by modulating MYC-Threonine 58 phosphorylation in PC3 cells. MYCi361 (6 μM; 24 h) also potently suppressed the expression of MYC target genes CDC25A and MYB in MYCT58A-expressing cells. MYCi361 inhibited the viability of MYC-dependent cancer cells including prostate cancer (MycCaP, LNCaP, and PC3), leukemia (MV4-11), lymphoma (HL-60 and P493-6), and neuroblastoma (SK-N-B2) with low-micromolar IC50 values. MYCi361 treatment of FVB mice bearing established MycCaP tumor allografts at 100 mg/kg/day induced tumor regression[2].
作用机制
MYCi361 binds to amino acids 366–378 of the MYC protein[2].
MYCi361 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Primary prostate cancer cells
6 μM
48 hours
To evaluate the proliferation inhibition effect of MYCi361 on primary prostate cancer cells with high and low expression of circ_0057558
Front Cell Dev Biol. 2021 Feb 26;9:644397.
MycCaP cells
4 μM
72 hr
Assess immunogenic cell death markers
Cancer Cell. 2019 Nov 11;36(5):483-497. e15
PC3 cells
6 μM
30 min
Assess binding of 361 to MYC protein
Cancer Cell. 2019 Nov 11;36(5):483-497. e15
MYCi361 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NOD/SCID/IL2rg-/- (NSG) mice
Patient-derived xenograft (PDX) model
Intraperitoneal injection
55 mg/kg/day
Once a week for 42 days
To evaluate the anti-tumor effect of MYCi361 on PDX models with high and low expression of circ_0057558
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