MRTX-1719 is a highly potent, orally bioavailable, and selective inhibitor of the PRMT5•MTA complex, exhibiting IC50 values of 3.6 nM and 20.5 nM for PRMT5•MTA and PRMT5, respectively. It binds tightly to the PRMT5•MTA complex, with a KD value of 0.14 pM. MRTX-1719 demonstrates antineoplastic activity both in vitro and in vivo, making it a valuable tool for cancer research [1][2].
体内研究
MRTX1719 (12.5-100 mg/kg/day orally for 21 days) leads to a reduction in tumor growth in Lu-99 orthotopic xenograft tumor model [2].
体外研究
Following a 10-day treatment, MRTX-1719 inhibits PRMT5 activity in MTAP-deleted HCT116 cells, not in wild-type cells, with an IC50 of 8 nM [1].
MRTX1719 (10-day treatment) reduces cell viability in MTAP-deleted HCT116 cells with an IC50 of 12 nM and in parental HCT116 cells with an IC50 of 890 nM [1].
MRTX-1719 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Murine CD8+ T cells
0.1 μM and 0.5 μM
3 days
Evaluate the effect of MRTX1719 on T cell function. Results showed MRTX1719 reduced SDMA levels at high concentration but had minimal impact on cytokine production and cytotoxicity.
J Immunother Cancer. 2024 Sep 23;12(9):e009600
B16 Mtap-KO tumor cells
0.1 μM and 0.5 μM
5 days
Evaluate the effect of MRTX1719 on growth and SDMA levels in MTAP-deleted tumor cells. Results showed MRTX1719 significantly inhibited growth and reduced SDMA levels in Mtap-KO cells but had minimal effects on WT cells.
J Immunother Cancer. 2024 Sep 23;12(9):e009600
MC38/gp100 Mtap-KO tumor cells
0.1 μM and 0.5 μM
5 days
Evaluate the effect of MRTX1719 on growth and SDMA levels in MTAP-deleted tumor cells. Results showed MRTX1719 significantly inhibited growth and reduced SDMA levels in Mtap-KO cells but had minimal effects on WT cells.
J Immunother Cancer. 2024 Sep 23;12(9):e009600
MTAP-deleted CRC cell lines
9.14, 27.43, 82.3, 246.9 nM
7 days
Evaluate the growth inhibitory effect of MRTX1719 on MTAP-deleted CRC cell lines, showing high sensitivity of MTAP-deleted cells to MRTX1719.
Mol Oncol. 2024 Jun;18(6):1460-1485
MRTX-1719 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
MC38/gp100 Mtap-KO and B16 Mtap-KO tumor models
Oral
30 mg/kg/day
Once daily for 7 or 14 days
Evaluate the antitumor efficacy of MRTX1719 in combination with anti-PD-1 in MTAP-deleted tumors. Results showed combination therapy significantly inhibited tumor growth and improved survival.
J Immunother Cancer. 2024 Sep 23;12(9):e009600
BALB/c nude mice
Subcutaneous xenograft model
Intraperitoneal injection
10 mg/kg
Once daily, continuous treatment
Evaluate the inhibitory effect of MRTX-1719 on MTAP-deficient gliomas in vivo, results showed that MRTX-1719 significantly reduced the volume of Hs683 xenografts, but the inhibitory effect was weakened in mixed xenografts
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