For research use only. Not for therapeutic Use.
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].
MRT-2359 demonstrates significant selective activity in MYC-driven lung cancer. In a broad range of cancer cell lines, MRT-2359 exhibits pronounced and preferential anti-proliferative activity towards those cell lines with high N-Myc or L-Myc expression, such as non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines. However, MRT-2359 shows minimal to no effect on cell lines with low N-Myc or L-Myc expression[4].
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].
| Catalog Number | I041288 |
| CAS Number | 2803881-11-8 |
| Synonyms | [2-(2,6-dioxopiperidin-3-yl)-3-oxo-1H-isoindol-5-yl]methyl N-[2-fluoro-5-(trifluoromethoxy)phenyl]carbamate |
| Molecular Formula | C22H17F4N3O6 |
| Purity | ≥95% |
| InChI | InChI=1S/C22H17F4N3O6/c23-15-4-3-13(35-22(24,25)26)8-16(15)27-21(33)34-10-11-1-2-12-9-29(20(32)14(12)7-11)17-5-6-18(30)28-19(17)31/h1-4,7-8,17H,5-6,9-10H2,(H,27,33)(H,28,30,31) |
| InChIKey | HNTGMIGBGVFOBT-UHFFFAOYSA-N |
| SMILES | C1CC(=O)NC(=O)C1N2CC3=C(C2=O)C=C(C=C3)COC(=O)NC4=C(C=CC(=C4)OC(F)(F)F)F |
| Reference | [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 |
