| Identification | Back Directory | [Name]
MRT-2359 | [CAS]
2803881-11-8 | [Synonyms]
MRT-2359
[2-(2,6-Dioxo-3-piperidinyl)-2,3-dihydro-3-oxo-1H-isoindol-5-yl]methyl N-[2-fluoro-5-(trifluoromethoxy)phenyl]carbamate | [Molecular Formula]
C22H17F4N3O6 | [MOL File]
2803881-11-8.mol | [Molecular Weight]
495.38 |
| Chemical Properties | Back Directory | [Boiling point ]
644.0±55.0 °C(Predicted) | [density ]
1.548±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted) | [form ]
Solid | [pka]
10.68±0.40(Predicted) | [color ]
White to off-white | [InChIKey]
HNTGMIGBGVFOBT-UHFFFAOYSA-N | [SMILES]
C(OCC1C=CC2=C(C=1)C(=O)N(C1CCC(=O)NC1=O)C2)(=O)NC1=CC(OC(F)(F)F)=CC=C1F |
| Hazard Information | Back Directory | [Uses]
MRT-2359 is a potent, orally active and selective GSPT1 depressant (IC50: >30 nM and <300 nM) that specifically induces apoptosis dependent on protein translation. MRT-2359 exhibits significant and preferred anti-proliferative activity in a variety of cancer cell lines, especially MYC-driven cell lines, such as non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with high expression of N-Myc or L-Myc. MRT-2359 inhibits the growth of drug-resistant NSCLC and SCLC cells, making it suitable for cancer research[1][2][3][4][5]. | [in vivo]
MRT-2359 completely degrades GSPT1 in high N-MYC non-small cell lung cancer (NSCLC) transplanted tumors and PDX models, reduces the expression level of N-Myc protein, consequently leading to a reduction in tumor size[3].
MRT-2359 (10 mg/kg; Oral gavage (p.o.); 5 days on, 9 days off, 4 weeks) can completely regress tumors in immunocompromised xenografted mouse models of AR-V7-positive cell lines 22RV1 and NCI-H660[5].
| [References]
[1] Gavory G, et al. Development of MRT-2359, an orally bioavailable GSPT1 molecular glue degrader, for the treatment of lung cancers with MYC-induced translational addiction[J]. Cancer Research, 2023, 83(7_Supplement): 3449-3449.
[2] Fasching Bernhard, et al. Preparation of isoindolinone compounds as modulators of cereblon. Patent. WO2022152821.
[3] Gerald Gavory, et al. Abstract 3929: Identification of MRT-2359 a potent, selective and orally bioavailable GSPT1-directed molecular glue degrader (MGD) for the treatment of cancers with Myc-induced translational addiction. Cancer Res 15 June 2022; 82 (12_Supplement): 3929.
[4] Gerald Gavory, et al. Abstract 3449: Development of MRT-2359, an orally bioavailable GSPT1 molecular glue degrader, for the treatment of lung cancers with MYC-induced translational addiction. Cancer Res 1 April 2023; 83 (7_Supplement): 3449.
[5] Ralph Tiedt, et al. Abstract 3294: The GSPT1 molecular glue degrader MRT-2359 is active against prostate cancer. Cancer Res 15 March 2024; 84 (6_Supplement): 3294 |
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