1371574-25-2

Upstream product

• 611-99-4 4,4'-Dihydroxybenzophenone 
• 177748-17-3 (E)-1-(4-hydroxyphenyl)-1-[4-(trimethylacetoxy)phenyl]-2-phenylbut-1-ene 
• 114031-67-3 [4-(4-hydroxybenzoyl)phenyl]-2,2-dimethyl propanoate 
• 112004-83-8 [4-[4-(2,2-dimethylpropanoyloxy)benzoyl]phenyl] 2,2-dimethylpropanoate 
• 1371574-23-0 (4-{(E/Z)-1-[4-(2-bromoethoxy)phenyl]-2-phenylbut-1-enyl}phenoxy)-tert-butyldimethylsilane 
• 74-89-5 methylamine 

Relevant academic research and scientific papers

Gefitinib-Tamoxifen Hybrid Ligands as Potent Agents against Triple-Negative Breast Cancer

Anticancer drug conjugates may benefit from simultaneous action at two targets potentially overcoming the drawbacks of current cancer treatment, such as insufficient efficacy, high toxicity, and development of resistance. Compared to a combination of two single-target drugs, they may offer an advantage of pharmacokinetic simplicity and fewer drug-drug interactions. Here, we report a series of compounds connecting tamoxifen or endoxifen with the EGFR-inhibitor gefitinib via a covalent linkage. These hybrid ligands retain both ER antagonist activity and EGFR inhibition. The most potent analogues exhibited single-digit nanomolar activities at both targets. The amide-linked endoxifen-gefitinib drug conjugates 17b and 17c demonstrated the most favorable anti-cancer profile in cellular viability assays on MCF7, MDA-MB-231, MDA-MB-468, and BT-549 breast cancer cells. Most importantly, in TNBC cells 17b and 17c displayed nanomolar IC50-values (380 nM - 970 nM) and were superior in their anti-cancer activity compared to their control compounds and combinations thereof.

Design, synthesis and biochemical evaluation of estrogen receptor ligand conjugates as tumour targeting agents

The estrogen receptors (ERα and ERβ), are ligand inducible nuclear receptors which play a key role in many cellular functions through specific gene expression regulation. The estrogen receptor is regarded as an attractive therapeutic target for hormone-dependent breast cancers. The antiestrogen drug tamoxifen is useful in the treatment of breast cancer. To develop new ER targeting agents as probes of estrogen receptor action, the synthesis and preliminary biochemical evaluation of five structurally varied estrogen receptor ligand conjugates containing the tamoxifen metabolite endoxifen are now reported. These structurally varied conjugates bind to the estrogen receptor (commonly overexpressed in breast cancer cells) and contain DNA alkylating, aromatase inhibitor and COX2 inhibitor moieties. The ER targeting group endoxifen (E/Z 4-hydroxy-N-desmethyltamoxifen) was selected for its ability to bind to the estrogen receptor. Compound 11 exhibited moderate antiproliferative activity IC50 = 1.64 μM in MCF-7 breast cancer cells, while compound 9b demonstrated the most potent ER binding effects with IC50 values of 35.6 nM(ERα), 19.5 nM(ERβ).