ERα 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.

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).

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.

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.

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.

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.

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

PVTX-321 (Compound 16a) is an orally active estrogen receptor α (ERα) degrader. PVTX-321 can potently degrade ERα (DC₅₀=0.15 nM in MCF-7 cells) and also has inhibitory activity against mutant ERα (IC₅₀=59 nM). PVTX-321 is promising for research of ER+/HER2- breast cancer.

THIQ-40 is a tetrahydroisoquinoline-based, orally active, and selective estrogen receptor ERα degrader (SERD) (IC₅₀=17 nM), with antitumor efficacy. THIQ-40 possesses functional ERα antagonistic activity, promotes ERα degradation and forms stable ERαLBD complexes. THIQ-40 shows the characteristic of rapid racemization in multi-species plasma. THIQ-40 can be widely applied to studies on the relevant mechanisms and drug development of ERα-positive breast cancer.

PROTAC ERα Degrader-13 is an orally active PROTAC molecule that efficiently and selectively degrades ERα (DC₅₀ = 3.78 nM). PROTAC ERα Degrader-13 has the characteristics of strong anti proliferation (IC₅₀ = 0.6 nM), induction of apoptosis, and overcoming drug resistance in MCF-7 cells. PROTAC ERα Degrader-13 has good safety and no significant organ toxicity. PROTAC ERα Degrader-13 can be used for cancer research.

NCP07 is a PROTAC degrader targeting the coactivator-binding site (CBS) of ERα. NCP07 induces the formation of the ERα-NCP07-VHL ternary complex and promotes ERα degradation via the ubiquitin-proteasome system. NCP07 induces apoptosis and cell cycle arrest in endocrine therapy-resistant breast cancer cells. NCP07 inhibits the proliferation of wild-type and ESR1-mutant breast cancer cells. NCP07 is applicable to breast cancer-related research.

ERα degrader 11 (compound B16) is a selective ERα degrader that can be used as an estrogen receptor probe to investigate ER status in ER-positive breast cancer cells.

F0840-0093 is a highly selective estrogen receptor α (ERα) degrader. F0840-0093 exhibits potent antiproliferative activity against T47D cells with an IC₅₀ value of 4.65 μM. F0840-0093 is promising for research of estrogen receptor-positive (ER+) breast cancer.

ERD-12310A is an orally active ERα PROTAC degrader, with a K_i value of 0.95 nM against human ERα and a DC₅₀ of 47 pM for ERα in MCF-7 cells. ERD-12310A forms a ternary complex with ERα and the CRBN E3 ubiquitin ligase, thereby inducing ubiquitination and proteasomal degradation of wild-type and ESR1^Y537S mutant ERα. ERD-12310A induces tumor regression in ER+ breast cancer xenografts and inhibits tumor growth in ESR1^Y537S mutant breast cancer xenografts. ERD-12310A can be used in studies related to ER-positive breast cancer and ESR1-mutant breast cancer.

GNE-5472 is a potent bifunctional ERα PRRTAC degrader, with its E3 ligand being a pan-IAP antagonist. GNE-5472 antagonizes cIAP1/2, activating the non-classical NF-κB pathway, resulting in a significant upregulation of TNFα expression. GNE-5472 inhibits the proliferation of breast cancer cells and induces cell apoptosis. GNE-5472 can be used for the study of breast cancer.

PROTAC ERα Degrader-12 is a potent and selective Erα PROTAC degrader. PROTAC ERα Degrader-12 has antiproliferative effects in multiple breast cancer cell lines with wild-type or mutant ERα. PROTAC ERα Degrader-12 can halt the cell cycle and induce cell apoptosis. PROTAC ERα Degrader-12 exhibits excellent antitumor and ERα degradation activity. PROTAC ERα Degrader-12 can be used for research on breast cancer.

X15695 is selective and orally active estrogen receptor (ERα) degrader. X15695 is an aryl hydrocarbon receptor (AHR) ligand. X15695 enables AHR to form a complex with the ERα, promoting its proteasomal degradation. X15695 inhibits the breast cancer cells proliferation, promotes cell cycle block and induces apoptosis. X15695 can be used for the study of breast cancer.

ER degrader 12 (Example 1) is an estrogen receptor (ER) degrader with IC₅₀ values for ERα and ERβ of 2.3 and 80.2 nM respectively (TR-FRET experiment). ER degrader 12 inhibits the proliferation of MCF-7 cells, with an IC₅₀ of 1.53 nM. ER degrader 12 can be used for research on breast cancer.