Estrogen Receptor/ERR Degrader

Giredestrant (GDC-9545) is an orally active, full, selective Estrogen receptor α (ERα) degrader and antagonist with a DC₅₀ of 0.03 nM. Giredestrant promotes the degradation of ERα protein, including the ESR1^Y537S mutant ERα. Giredestrant reduces uterine wet weight in immature rats and induces a low cuboidal phenotype in their endometrial epithelium. Giredestrant induces tumor regression in both ESR1^Y537S mutant and wild-type ERα tumor models. Giredestrant can be used for the research of ER⁺ breast cancer.

Imlunestrant (LY-3484356) is an orally active, potent and selective estrogen receptor degrader (SERD) with pure antagonistic properties. Imlunestrant results in sustained inhibition of ER-dependent gene transcription and cell growth. Imlunestrant can be used for the research of ER-positive (ER+) advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC).

AZD9496 is an effective, selective estrogen receptor (ERα) antagonist with an IC₅₀ of 0.28 nM. AZD9496 is an orally active, selective estrogen receptor degrader (SERD).

Imlunestrant (LY-3484356) tosylate is an orally active, potent and selective estrogen receptor degrader (SERD) with pure antagonistic properties. Imlunestrant tosylate results in sustained inhibition of ER-dependent gene transcription and cell growth. Imlunestrant tosylate can be used for the research of ER-positive (ER+) advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC).

ERD-308 is a potent estrogen receptor (ER) PROTAC degrader. ERD-308 has DC₅₀ values of 0.17 nM and 0.43 nM in MCF-7 and T47D ER+ cells. ERD-308 can inhibit the proliferation of breast cancer cells and exhibits anti-tumor activity.

SAR439859 (compound 43d) is an orally active, non-steroidal, and selective estrogen receptor degrader (SERD). SAR439859 is an effective ER antagonist with ER degradation activity, an EC₅₀ of 0.2 nM. SAR439859 can show potent anti-tumor effects and limited cross-resistance in ER⁺ breast cancer.

LSZ-102 is a potent, orally bioavailable, selective estrogen receptor degrader (SERD) with an IC₅₀ value of 0.2 nM.

UT-34 is a potent, selective, orally bioactive second-generation pan-androgen receptor (AR) antagonist and degrader, with IC₅₀ values of 211.7 nM, 262.4 nM, and 215.7 nM for wild-type AR, F876L-AR, and W741L-AR, respectively. UT-34 binds to the ligand-binding domain (LBD) and functional 1 (AF-1) domain of AR and requires the ubiquitin-proteasome pathway for AR degradation. UT-34 has anti-prostate cancer effects.

PROTAC ERα Degrader-2 is a ERα PROTAC degrader. PROTAC ERα Degrader-2 significantly down-regulates the level of ERα in MCF-7 cells.

ERD-3111 is an orally active PROTAC degrader targeting estrogen receptor α (ERα), with a DC₅₀ of 0.5 nM. ERD-3111 induces ERα degradation in breast cancer cells, and triggers tumor regression or complete inhibition of tumor growth in ER-positive breast cancer xenograft models. ERD-3111 can be used in breast cancer-related research.

PROTAC ERα Degrader-4 (Compound ZD12) is a highly potent and selectivePROTAC ERα degrader (K_i: 5.08 μM). PROTAC ERα Degrader-4 contains OBHSAs, linker and E3 ligase ligands. PROTAC ERα Degrader-4 shows excellent cell inhibitory and ERα degradation activity against Tamoxifen-sensitive and -resistant ER⁺ breast cancer (BC) cells and ERα-mutated BC cells. PROTAC ERα Degrader-4 can induce apoptosis and can be used for cancer research.

Taragarestrant (D-0502) meglumine is a potent, orally active and selective estrogen receptor degrader (SERD). Taragarestrant meglumine shows potent activity in various ER+ breast cancer cell lines and xenograft models.

PHTPP-1304 is a PHTPP-based autophagy targeting chimera (AUTOTAC). PHTPP-1304 induces the degradation of estrogen receptor ERβ through the autophagy pathway, rather than ubiquitination (DC₅₀ ≈ 2 nM, in HEK293T cells; < 100 nM in ACHN renal carcinoma and MCF-7 breast cancer cells). PHTPP-1304 can induce the self-oligomerization of p62. PHTPP-1304 can be used to study various cancers mediated by ERβ.

PROTAC ERα Degrader-6 (compound A2) is a potent PROTAC degrader of ERα, with IC₅₀ of 0.11 μM in MCE-7 cells. PROTAC ERα Degrader-6 has anti-tumor effect. PROTAC ERα Degrader-6 is a fluorescent probes with Em of 582 nm that enable real-time visualization of ERα protein degradation.

GNE-274 is a structural analog of the ER degrader GDC-0927 and is a non-degrader. GNE-274 does not induce conversion of ER in breast cancer cell lines and functions as a partial ER agonist (partial ER agonist). GNE-274 increases the chromatin accessibility of ER-DNA binding sites, whereas GDC-0927 does not. GNE-274 is an effective ER ligand binding domain (LBD) inhibitor. GNE-274 can be used in cancer research.

PROTAC_ERRα is a potent and selective ERRα PROTAC degrader (DC₅₀: ~100 nM in MCF-7 cells). PROTAC_ERRα recruits the VHL E3 ubiquitin ligase to ERRα, inducing ERRα ubiquitination and proteasomal degradation in a VHL-dependent manner. PROTAC_ERRα can be used in breast cancer-related research.

GLL398 is a potent, orally bioavailable selective estrogen receptor degrader (SERD) with an IC₅₀ value of 1.14 nM. GLL398 shows a strong dose-dependent binding to ER with a mutation at Y537S (IC₅₀=29.5 nM). GLL398 blocks tumor growth in xenograft models of breast cancer.

OP-1074, a pure anti-estrogen drug, is a selective ER degrader (PA-SERD) with specific anti-estrogenic activity against ERα and ERβ, inhibiting 17β-estradiol (E2)-stimulated transcription with IC₅₀ values of 1.6 and 3.2 nM, respectively.

GDC-0927 Racemate (SRN-927 Racemate) is an estrogen receptor (ER) degrader that can effectively inhibit the activity of ER-α with an IC₅₀ value of 0.2 nM and can be used in diseases related to estrogen receptors.

Taragarestrant (D-0502) is a potent, orally active and selective estrogen receptor degrader (SERD). Taragarestrant shows potent activity in various ER+ breast cancer cell lines and xenograft models.