protac er degrader 2

PROTAC ER Degrader-2 serves as a synthesis intermediate for the production of PAC, a compound that incorporates the ADCs linker and PROTACs, which are subsequently conjugated to an antibody. PAC, exhibits a greater capability to degrade estrogen receptor-alpha (ERα) compared to PROTAC (without the presence of an antibody)[1].

PROTAC ERα Degrader-2 is composed of a cIAP1 ligand binding group, a linker, and an estrogen receptor α (ERα) binding group, serving as an ERα degrader. It achieves maximal ERα degradation in human mammary tumor MCF7 cells at a concentration of 30 μM. Degradation inducers that utilize cIAP1 are referred to as specific and non-genetic IAP-dependent protein erasers (SNIPERs)[1].

Vepdegestrant (ARV-471) is a selective and highly potent estrogen receptor (ER, ESR1) PROTAC degrader with strong degrading activity against the ER protein. By directly degrading the ER protein rather than merely antagonizing its activity, vepdegestrant effectively inhibits the ER signaling pathway and demonstrates significant antitumor activity in ER-positive (ER⁺) breast cancer, with a DC50 value of approximately 2 nM. It is particularly effective against tumors harboring ESR1 mutations.

ER ligand-2 is a ligand for ER. It can be used in the synthesis of PROTAC ER Degrader-11.

PROTAC ER Degrader-14 (compound 86) is a PROTAC-type estrogen receptor/ERR degrader. It comprises an E3 ubiquitin ligase ligand (blue part) (S)-Deoxy-thalidomide, a PROTAC linker (black part) N-Boc-piperazine, and a target protein ligand (red part) ER ligand-6. The combination of the E3 ligase and linker forms tert-Butyl (S)-4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperazine-1-carboxylate.

ER ligand-12 is a ligand of the estrogen receptor (ER) that can be utilized in the synthesis of PROTACs, such as PROTACER Degrader-2.

Vepdegestrant-d5 (ARV-471-d5) is the deuterium-labeled version of Vepdegestrant. Vepdegestrant (ARV-471) serves as an orally active estrogen receptor PROTAC degrader used in combating breast cancer. This heterobifunctional molecule facilitates the interaction between estrogen receptor α and the intracellular E3 ligase complex, leading to ubiquitination and subsequent degradation of the estrogen receptor via the proteasome. Vepdegestrant effectively degrades estrogen receptors in ER-positive breast cancer cell lines, with a DC50 of approximately 2 nM.

(Rac)-Vepdegestrant is an isomer of Vepdegestrant. Vepdegestrant ((Rac)-ARV-471) is an orally active estrogen receptor PROTAC degrader used against breast cancer. It is a heterobifunctional molecule that facilitates the interaction between estrogen receptor α and the intracellular E3 ligase complex. Vepdegestrant induces ubiquitination and subsequent degradation of the estrogen receptor via the proteasome, effectively degrading ER in ER-positive breast cancer cell lines with a DC50 value of approximately 2 nM.