composition

Tos-PEG4-t-butyl ester (Tos-PEG4-Boc) is a PROTAC linker characterized by its PEG composition, crucial in synthesizing various PROTACs, including BI-3663, a selective PTK2 FAK PROTAC. Using cereblon ligands, it targets E3 ligases to degrade PTK2, exhibiting potent inhibitory activity with an IC50 of 18 nM[1].

Boc-Pip-alkyne-Ph-COOH, a PROTAC linker characterized by its alkyl ether composition, plays a crucial role in synthesizing PROTACs including ARD-266. This compound demonstrates significant efficacy in promoting the degradation of androgen receptor (AR) protein across AR-positive prostate cancer cell lines such as LNCaP, VCaP, and 22Rv1, showcasing DC50 values ranging from 0.2-1 nM[1].

NH2-PEG5-C6-Cl (K-7) is a PROTAC linker characterized by its PEG composition. It can be utilized in the synthesis of various PROTACs, facilitating the degradation of intracellular molecules via autophagy[1].

Phthalimide-PEG4-MPDM-OH, a PROTAC linker with a PEGs composition, has applications in the synthesis of various PROTACs. These PROTACs consist of a linker connecting two distinct ligands: one binds to an E3 ubiquitin ligase, while the other binds to the target protein. By leveraging the intracellular ubiquitin-proteasome system, PROTACs selectively induce the degradation of target proteins [1].

S-(1-Hydroxy-2-methylpropan-2-yl) methanesulfonothioate, an ADC linker, is a glutathione-cleavable compound used for attaching monoclonal antibodies (mAb) in antibody-drug conjugates (ADCs), specifically referring to the Alkyl-Chain composition of the linker portion of these molecules [1].

DZ-837 is a PROTAC that targets the BCL6 protein. The composition of DZ-837 includes the BCL6 ligand-2, the E3 ubiquitin ligase ligand Thalidomide-4-OH, and a PROTAC Linker. The configuration notably features a conjugate of the E3 ubiquitin ligase ligand and the Linker, designated as 2-(2,6-Dioxopiperidin-3-yl)-4-((2-(2-hydroxyethoxy)ethyl)amino)isoindoline-1,3-dione.

JMV7048 is an effective PROTAC degrader targeting the PXR (Pregnane X Receptor), with a DC50 of 379 nM. It induces the polyubiquitination and degradation of PXR protein by recruiting the E3 CRBN ubiquitin ligase and the 26S proteasome. This degradation of PXR significantly enhances the chemosensitivity of colorectal cancer stem cells, substantially delaying cancer recurrence in vivo. The composition of JMV7048 includes the PXR agonist JMV6944, a linker, and Thalidomide 5-fluoride.

SIAIS039 is an orally active PROTAC specifically targeting c-ros oncogene 1 (ROS1), demonstrating DC50 values of 154.46 nM, 126.47 nM, and 143.69 nM in HCC78 cells, Ba F3 cells expressing CD74-ROS1 fusion, and Ba F3 cells expressing SDC4-ROS1 fusion, respectively. This compound inhibits proliferation, induces cell cycle arrest, and triggers apoptosis in ROS1-positive cells, while also inhibiting colony formation. In vivo, SIAIS039 exhibits potent anti-tumoral activity against ROS1-driven tumor growth. The composition of SIAIS039 includes the ALK inhibitor Brigatinib, linker EM-12, and VHL E3 ubiquitin ligase ligand.