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.
PROTACCDK9 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].
PROTAC CBP P300 Degrader-1 is an effective compound that degrades CBP P300 in a potent manner. It significantly reduces cell viability in various cancer cell lines.
PROTAC IDO1 Degrader-1 is the first potent IDO1 (indoleamine 2,3-dioxygenase 1) degrader that hijacks IDO1 to CRBN E3 ligase to introduce IDO1 into UPS and eventually achieve ubiquitination and degradation (DC50=2.84 μM). PROTAC IDO1 Degrader-1 moderately improves the tumor-killing activity of H ER2 CAR-T cells[1]. PROTAC IDO1 Degrader-1 (compound 2c) (10 μM; 24 hours) notably decreases IDO1 level induced by IFN-γ[1].PROTAC IDO1 Degrader-1 and IFN-γ (5 ng mL) are incubated with HeLa cells for 24 h, and a significant dose-dependent degradation is observed. PROTAC IDO1 Degrader-1 combined with chimeric antigen receptor-modified T (CAR-T) cells can improve the tumor-killing activity of HER-2 CAR-T cells[1].PROTAC IDO1 Degrader-1 induces significant and persistent degradation of IDO1 with maximum degradation (dmax) of 93% in HeLa cells[1]. [1]. Hu M, et al. Discovery of the first potent proteolysis targeting chimera (PROTAC) degrader of indoleamine 2,3-dioxygenase 1. Acta Pharm Sin B. 2020;10(10):1943-1953.
PROTAC BRD4 Degrader-9 (compound 8a) is a novel chemical compound consisting of ligands for von Hippel-Lindau and BRD4, connected by a PROTAC moiety. This compound can effectively degrade the BRD4 protein in PC3 prostate cancer cells. When conjugated with STEAP1 and CLL1 antibodies, PROTAC BRD4 Degrader-9 exhibits potent activity, with respective DC50 values of 0.86 nM and 7.6 nM.
PROTAC ERRα Degrader-3 is a highly effective and selective von Hippel-Lindau-based ligand that efficiently degrades the ERRα protein. At a concentration of 30 nM, this compound exhibits a remarkable degradation capability, reducing the ERRα protein levels by >80%. Importantly, PROTAC ERRα Degrader-3 shows no activity against the ERRβ and ERRγ proteins.
PROTAC BRD4 degrader for PAC-1 (compound 5) is a chimeric BET degrader GNE-987 conjugated with a disulfide-containing linker[1]. This PROTAC-linker conjugate specifically targets and degrades BRD4, enabling selective proteolysis of PAC-1.
Halo PROTAC 1 is a PROTAC, which is a ligand having activity to bind to an intracellular proteins fused with HaloTag and a structure having activity to induce autophagy of an intracellular molecule are linked via a PEG linker[1].
(rel)-PROTAC ERRα Degrader-1 is a relative configuration of PROTAC ERRα Degrader-1, which is an estrogen-related receptor alpha (ERRa) degrader. PROTAC ERRα Degrader-1 consists of an MDM2 ligand binding moiety, a linker and an ERRa binding moiety [1].
PROTAC FKBP Degrader-3 is a PROTAC that comprises a FKBP ligand binding group, a linker and an VHL binding group. PROTAC FKBP Degrader-3 is a potent FKBP degrader[1].
PROTAC MDM2 Degrader-4 is a compound designed using PROTAC technology to degrade MDM2. It combines a powerful MDM2 inhibitor, a linker, and the MDM2 ligand for E3 ubiquitin ligase[1].
PROTAC FLT-3 degrader 1 is a PROTAC FLT-3 degrader of internal tandem duplication (ITD) with an IC50 of 0.6 nM and exhibits anti-proliferative activity.