Description
CB-103 (218457-67-1) is an orally active inhibitor of the Notch signaling activation complex (IC50’s from 0.9 to 3.9 μM in various cell-based assays), the most downstream level of the Notch signaling pathway. It inhibited the growth of Notch-addicted human T cell acute lymphoblastic leukemia cells as well as other cell lines. CB-103 also inhibited the growth of human breast cancer and leukemia xenografts without the intestinal toxicity associated with γ-secretase Notch inhibitors.
Uses
Limantrafin (CB-103) is a first-in-class, orally active protein-protein interaction (PPI) inhibitor of the NOTCH transcriptional activation complex. Limantrafin has anti-tumor activity[1][2][3][4].
in vivo
Limantrafin inhibits NOTCH dependent cellular processes in mice[2].
Limantrafin blocks in vivo growth of PDX models of T-ALL[2].
Limantrafin (25 mg/kg; i.p./p.o.; 2x daily; for 2 weeks) inhibits growth of GSI/Mab resistant triple negative breast cancer[3].
Limantrafin exhibits anti-tumor activity in xenograft models of human T-ALL and mouse mammary tumors[3].
| Animal Model: | NSG mice, triple negative breast cancer mouse xenograft model[3] |
| Dosage: | 25 mg/kg |
| Administration: | Oral administration/Intraperitoneal injection; 2x daily; for 2 weeks |
| Result: | Inhibited growth of GSI/Mab resistant triple negative breast cancer. |
References
[1] RAJWINDER LEHAL. Pharmacological disruption of the Notch transcription factor complex.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2020: 16292-16301. DOI:
10.1073/pnas.1922606117
