For research use only. Not for therapeutic Use.
Vepdegestrant (ARV-471) is an orally active PROTAC estrogen receptor degrader against breast cancer. Vepdegestrant is a hetero-bifunctional molecule that facilitates the interactions between estrogen receptor alpha and an intracellular E3 ligase complex. Vepdegestrant leads to the ubiquitylation and subsequent degradation of estrogen receptors via the proteasome. Vepdegestrant robustly degrades ER in ER-positive breast cancer cell lines with a half-maximal degradation concentration (DC50) of about 2 nM[1].
Vepdegestrant (10 and 100 nM, 3 days) increases MHC-I expression in MCF7 cells expressing the Y537S ER mutation (ER-Y537S)[3].
Vepdegestrant (3-30 mpk, p.o, daily) inhibits tumor growth in estradiol-dependent MCF7 xenografts and reduces tumor ER protein[2].
| Catalog Number | I044589 |
| CAS Number | 2229711-68-4 |
| Synonyms | (3S)-3-[6-[4-[[1-[4-[(1R,2S)-6-hydroxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl]phenyl]piperidin-4-yl]methyl]piperazin-1-yl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione |
| Molecular Formula | C45H49N5O4 |
| Purity | ≥95% |
| InChI | InChI=1S/C45H49N5O4/c51-37-12-15-39-33(27-37)8-13-38(31-4-2-1-3-5-31)43(39)32-6-9-35(10-7-32)48-20-18-30(19-21-48)28-47-22-24-49(25-23-47)36-11-14-40-34(26-36)29-50(45(40)54)41-16-17-42(52)46-44(41)53/h1-7,9-12,14-15,26-27,30,38,41,43,51H,8,13,16-25,28-29H2,(H,46,52,53)/t38-,41+,43+/m1/s1 |
| InChIKey | TZZDVPMABRWKIZ-XMOGEVODSA-N |
| SMILES | C1CC2=C(C=CC(=C2)O)C(C1C3=CC=CC=C3)C4=CC=C(C=C4)N5CCC(CC5)CN6CCN(CC6)C7=CC8=C(C=C7)C(=O)N(C8)C9CCC(=O)NC9=O |
| Reference | [1]. Lin X, et al. Targeting estrogen receptor α for degradation with PROTACs: A promising approach to overcome endocrine resistance. Eur J Med Chem. 2020;206:112689. [2]. JJ Flanagan, et al. Abstract P5-04-18: ARV-471, an oral estrogen receptor PROTAC degrader for breast cancer. [3]. Hermida-Prado F, et al. Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer. Cancer Res. 2023 Oct 2;83(19):3284-3304. |
