ER degrader 1

ER degrader 1 is a potent degrader of the estrogen receptor (ER) with potential applications in cancer treatment, as it targets the estrogen signaling system, which is crucial for cell growth, differentiation, and apoptosis.

ER degrader 10 (Compound 51) is an orally active estrogen receptor (ER) selective degrader and antagonist, with a DC50 of 0.43 nM and an IC50 of 0.56 nM. It inhibits the proliferation of ER-positive cells, with an IC50 ranging from 0 to 15 nM. ER degrader 10 exhibits weak inhibitory activity on the hERG channel, with an IC50 greater than 40 μM. It has blood-brain barrier permeability, with a brain plasma ratio (Kp) of 3.05. In mouse models, ER degrader 10 demonstrates antitumor activity.

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].

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.

Palazestrant (OP-1250) is an orally available and highly potent estrogen receptor antagonist and selective ER degrader with antitumor activity.Palazestrant inhibits 17b-estradiol (E2), inhibits MCF7 and CAMA-1 cell proliferation, and can be used in breast cancer research.

ER Degrader 2, a potent estrogen receptor (ER) degrader, plays a significant role in the estrogen signaling system, which is crucial for regulating cell growth, differentiation, and apoptosis. It holds promise for research in cancer diseases[1].

ER degrader 3, a potent estrogen receptor (ER) degrader, significantly impacts the estrogen signaling pathway, which is crucial for regulating cell growth, differentiation, and apoptosis. This compound holds potential for cancer research[1].

Imlunestrant tosylate (LY-3484356) is a potent, orally active selective estrogen receptor degrader (SERD) with purely antagonistic properties, effectively inhibiting estrogen receptor (ER)-dependent gene transcription and cell growth. This compound is applicable in research on ER-positive (ER+) advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC) [1] [2].

Taragarestrant (D-0502) meglumine is a potent, orally active, and selective estrogen receptor degrader (SERD) demonstrating significant efficacy in ER+ breast cancer cell lines and xenograft models [1][2].

ER degrader 4, a selective and orally active compound, effectively degrades estrogen receptors and exhibits anti-tumor activity [1].

ER Degrader 5 is a potent compound that degrades the estrogen receptor (ER), exhibits anti-proliferation activity, and has potential applications in breast cancer research [1].

AZD9496 deacrylic acid phenol (AZD9496) represents a portion of the ligand that targets the protein for PROTAC ER Degrader-4 [1].

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].

ER degrader 6 (compound 35s) is a potent selective estrogen receptor modulator (SERM) with the capacity to degrade Estrogen Receptor (ER)α. It disrupts the microtubule network, inhibits tubulin polymerization, and effectively suppresses tumor growth with minimal toxicity [1].

ER degrader 7 (Compound 35t) is a selective degrader of both ERα and ERβ and functions as a tubulin polymerization inhibitor. It inhibits cell viability with IC50 values of 0.06 μM for MCF-7, 2.56 μM for T47D, 15.84 μM for MCF-10A, 1.59 μM for LCC2, 1.67 μM for T47D D538G, and 1.37 μM for T47D Y537S cells. Additionally, ER degrader 7 demonstrates efficacy in suppressing breast cancer tumor growth [1].

Compound G-5b, an estrogen receptor modulator 10, functions as an estrogen receptor (ER) antagonist (IC50=6.7 nM) and degrader (DC50=0.4 nM). It has the capability to induce apoptosis and block cells at the G1 G0 phase, making it applicable in cancer research [1].

ER degrader 9 (compound 1) serves as a bifunctional molecule and an effective estrogen receptor (ER) degrader with a DC50 of ≤10 nM in MCF-7 cells. It is utilized in the research of breast cancer.