Synonyms: CB103
Compound class:
Synthetic organic
Comment: CB-103 is a first-in-class, small-molecule, orally active, pan-NOTCH inhibitor that is being investigated for anti-cancer potential [1-2]. It is being developed by Cellestia.
The CAS number provided within the full documentation for the study entitled 'A Phase I/IIA, Multi-Centre, Open-Label, Dose-Escalation Study with Expansion Arms to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CB-103 Administered Orally in Adult Patients with Advanced or Metastatic Solid Tumours and Haematological Malignancies Characterised by Alterations of the NOTCH Signalling Pathway' (EudraCT protocol 2017-001491-35) allowed us to identify a chemical structure for CB-103, frior to formal name>structure disclosure [2]. Information disclosed in meeting abstract form suggests that CB-103 acts by inhibiting protein-protein interactions that are required to establish assembly of the functional NOTCH transcription complex in the nucleus. By acting at the most downstream point in the NOTCH pathway, CB-103 inhibits NOTCH signalling independently of the mechanisms of NOTCH activation. NOTCH pathway signalling, and the approaches being explored for therapeutic targeting are reviewed by Sorrentino et al., 2019 [3]. |
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References |
1. Fabbro D, Bauer M, Murone M, Lehal R. (2020)
Notch Inhibition in Cancer: Challenges and Opportunities. Chimia (Aarau), 74 (10): 779-783. [PMID:33115560] |
2. Lehal R, Zaric J, Vigolo M, Urech C, Frismantas V, Zangger N, Cao L, Berger A, Chicote I, Loubéry S et al.. (2020)
Pharmacological disruption of the Notch transcription factor complex. Proc Natl Acad Sci U S A, 117 (28): 16292-16301. [PMID:32601208] |
3. Sorrentino C, Cuneo A, Roti G. (2019)
Therapeutic Targeting of Notch Signaling Pathway in Hematological Malignancies. Mediterr J Hematol Infect Dis, 11 (1): e2019037. [PMID:31308913] |