ChemicalBook--->CAS DataBase List--->2803881-11-8

2803881-11-8

2803881-11-8 Structure

2803881-11-8 Structure
IdentificationBack 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 PropertiesBack 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
Hazard InformationBack 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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