Table 2 Representative small molecules targeting protein degradation under clinical evaluation
From: Protein degradation: expanding the toolbox to restrain cancer drug resistance
Small molecules | Target | Application | Stage of development | Refs. |
|---|---|---|---|---|
KSQ-4279 | USP1 | Patients with advanced solid tumors alone or in combination with an oral PARPi | Phase I | NCT05240898 |
Perifosine | UCHL3 | Refractory tumors | Phase I or II | NCT00873457, NCT01049841, NCT00391560, NCT01097018, NCT00054145 |
VLX1570 | UCHL and USP14 | Multiple myeloma | Phase II | NCT02372240 |
AMG-232 | MDM2 | Treating patients with acute myeloid leukemia that has come back (recurrent), does not respond to treatment (refractory), or is newly diagnosed in combination with decitabine | Phase I | NCT03041688 |
ALRN-6924 | MDM2/MDMX | Treatment for resistant (refractory) pediatric cancer | Phase I | NCT03654716 |
DS-3032b | MDM2 | Treatment of relapsed and/or refractory multiple myeloma | Phase I | NCT02579824 |
RO6839921 | MDM2 | Patients with advanced cancers | Phase I | NCT02098967, NCT01462175 |
BI 907828 | MDM2 | Different types of advanced cancer | Phase I | NCT03449381, NCT05376800, NCT03964233 |
NX-1607 | Cbl-b | Advanced malignancies | Phase I | NCT05107674 |
KPG-818 | CRL4 | Hematological malignancies | Phase I | NCT04283097 |