natural

Thailanstatin A is an ultra-potent inhibitor of eukaryotic RNA splicing (IC50 = 650 nM). It inhibits multiple cancer cell lines via non-covalent binding to the SF3b subunit of the U2 snRNA subcomplex of the spliceosome, displaying low-nM to sub-nM IC50s. Thailanstatin A, as a payload for ADCs, is conjugated to the lysines on trastuzumab, yielding linker-less ADC.

ARV-393 is a PROTAC degrader targeting BCL6 with the advantage of being highly potent and orally available.ARV-393 recruits BCL6 and E3 ligase cerebellum to rapidly degrade BCL6 through the cell's natural ubiquitin proteasome system for the treatment of diffuse large b-cell lymphoma (DLBCL) and non-Hodgkin's lymphoma (NHL).

PROTAC CDK9 degrader-2 (compounds 11c) is a potent and selective CDK9 degrader based on PROTAC, with an IC50 of 17 μM in MCF-7 cell lines. Natural product Wogonin binds ubiquitin E3 ligase cereblon (CRBN) via a linker to form PROTAC[1].

AcLysValCit-PABC-DMAE-SW-163D is a drug-linker conjugate for antibody-drug conjugates (ADCs), incorporating the natural bis-intercalator SW-163D through an AcLysValCit-PABC-DMAE linker[1].

CDK9 Antagonist-1 (compounds 11c) is a potent and selective CDK9 degrader based on PROTAC, with an IC50 of 17 μM in MCF-7 cell lines. Natural product Wogonin binds ubiquitin E3 ligase cereblon (CRBN) via a linker to form PROTAC[1]. CDK9|17 μM (IC50, MCF-7 cells) [1]. Bian J , et al. Discovery of Wogonin-based PROTACs against CDK9 and capable of achieving antitumor activity. Bioorg Chem. 2018 Dec;81:373-381.