erα

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].

PROTAC ERα Degrader-1 is a chemical compound. It consists of a ubiquitin E3 ligase binding group, a linker, and a protein binding group. This compound serves as a degrader of estrogen receptor-alpha (ERα).

PROTACERα Degrader-10 (Compound 160a) is an orally bioavailable ERα degrader with a DC50 of 0.37-1.1 nM in MCF7, T47D, and CAMA-1 cells. It demonstrates antitumor activity in mouse models.

PROTACERα Degrader-6 (compound A3) is an effective PROTAC degrader of ERα with an IC50 of 0.12 μM in the MCE-7 cell line. It exhibits antitumor activity and serves as a fluorescent probe with an emission wavelength of 582 nm, enabling real-time visualization of ERα protein degradation.

PROTACERα Degrader-9 (Compound 18c) is a dual-targeting PROTAC degrader designed to diminish estrogen receptor α (ERα) and aromatase (ARO). It demonstrates a Ki of 0.25 μM for ERα binding and an IC50 of 4.6 μM for ARO inhibition. This compound curbs proliferation in wild-type MCF-7 cells (IC50=0.54 μM) and ERα mutant variants MCF-7EGFR (IC50=0.075 μM), MCF-7D538G (IC50=0.31 μM), and MCF-7Y537S (IC50=2.3 μM), while also downregulating ERS1 and MYC expression. PROTACERα Degrader-9 arrests the cell cycle at the G2/M phase and induces apoptosis in MCF-7 cells, exhibiting antitumor efficacy in mouse models.

PROTAC ERα Y537S degrader-1 consists of a ubiquitin E3 ligase binding group, a linker, and a protein binding group, functioning as an estrogen receptor-alpha (ERα) Y537S degrader [1].

PROTAC ERα Degrader-7 (Compound i-320) is a powerful PROTAC degrader targeting the estrogen receptor alpha (ERα), exhibiting a DC50 of 0.000006 µM. This compound consists of a cereblon-binding segment, LBM, connected to ERBM, an ERα-binding ligand that includes a benzofused partially saturated 6-membered carbocyclic or heterocyclic ring [1].

PROTAC ERα Degrader-8 (compound ii-56), a highly potent degrader of Erα, achieves a DC50 of just 0.000006 μM in MCF7 cells [1].

PROTAC ER Degrader-4 is a PROTAC degrader of the estrogen receptor (ER) with an IC50 of 0.8 nM.

Estrone-N-O-C1-amido (ERα ligand 1) is an estrogen ligand derivative of Estrone that specifically binds to estrogen receptor α (ERα). With a linker, it complexes with the cIAP1 ligand Bestatin, forming SNIPER[1].

PAC is a chemical conjugate consisting of an ADCs linker and PROTACs linked to an antibody. When PAC is conjugated to an antibody, it exhibits enhanced degradation of estrogen receptor-alpha (ERα) in comparison to PROTAC alone.

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 ER Degrader-3, an intermediate for the synthesis of PAC, specifically compound LP2. PAC serves as the linker for ADCs and PROTACs that are conjugated to an antibody. Notably, when PAC is conjugated to an antibody, it exhibits enhanced degradation of estrogen receptor-alpha (ERα) compared to PROTAC alone [1].

SNIPER(ER)-87 is a chemical compound composed of a derivative of the inhibitor of apoptosis protein (IAP) ligand LCL161 conjugated to the estrogen receptor α (ERα) ligand 4-hydroxytamoxifen using a PEG linker. It effectively degrades the ERα protein with an IC50 value of 0.097 μM. Within cells, SNIPER(ER)-87 selectively recruits XIAP to ERα, and XIAP functions as the primary E3 ubiquitin ligase responsible for the degradation of ERα induced by SNIPER(ER)-87[1][2].

ERD-12310A targets the estrogen receptor α (ERα) as a PROTAC with an ED50 value of 47 pM and possesses oral bioavailability.

ERD-3111 (Compound 44), an orally active PROTAC ERα degrader (DC50: 0.5 nM), exhibits efficacy in inhibiting tumor growth in both the parental MCF-7 xenograft model harboring wild-type ER and two ESR1-mutated mouse models. This compound has utility in the investigation of ER+ breast cancer [1].

VHL Ligand 14 (Compound 11), a VHL ligand engineered for creating PROTAC estrogen receptor α (ERα) degraders, exhibits a binding affinity with an IC50 of 196 nM [1].