Targeting the estrogen receptor with metal-carbonyl derivatives of estradiol

Hanson, Robert N.; Kirss, Rein U.; McCaskill, Emmett; Hua, Edward; Tongcharoensirikul, Pakamas; Olmsted, Sandra L.; Labaree, David; Hochberg, Richard B.

doi:10.1016/j.bmcl.2011.12.111

Cited by 10 publications

(4 citation statements)

References 52 publications

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“…Estrogenic steroid conjugates possessing metal chelates at the 17α-position represent an attractive delivery vector as a targeting strategy [ 89 , 90 , 91 , 92 ]. In this regard, Zhang et al synthesized a new series of estrogen-derived metal complexes and applied the squaramide structure as the core of the metal binding unit.…”

Section: Metal Complexesmentioning

confidence: 99%

Estrogen Receptor Ligands: A Review (2013–2015)

Farzaneh

Zarghi

2016

Sci. Pharm.

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Estrogen receptors (ERs) are a group of compounds named for their importance in both menstrual and estrous reproductive cycles. They are involved in the regulation of various processes ranging from tissue growth maintenance to reproduction. Their action is mediated through ER nuclear receptors. Two subtypes of the estrogen receptor, ERα and ERβ, exist and exhibit distinct cellular and tissue distribution patterns. In humans, both receptor subtypes are expressed in many cells and tissues, and they control key physiological functions in various organ systems. Estrogens attract great attention due to their wide applications in female reproductive functions and treatment of some estrogen-dependent cancers and osteoporosis. This paper provides a general review of ER ligands published in international journals patented between 2013 and 2015. The broad physiological profile of estrogens has attracted the attention of many researchers to develop new estrogen ligands as therapeutic molecules for various clinical purposes. After the discovery of the ERβ receptor, subtype-selective ligands could be used to elicit beneficial estrogen-like activities and reduce adverse side effects, based on the different distributions and relative levels of the two ER subtypes in different estrogen target tissues. Therefore, recent literature has focused on selective estrogen ligands as highly promising agents for the treatment of some types of cancer, as well as for cardiovascular, inflammatory, and neurodegenerative diseases. Estrogen receptors are nuclear transcription factors that are involved in the regulation of many complex physiological functions in humans. Selective estrogen ligands are highly promising targets for treatment of some types of cancer, as well as for cardiovascular, inflammatory and neurodegenerative diseases. Extensive structure-activity relationship studies of ER ligands based on small molecules indicate that many different structural scaffolds may provide high-affinity compounds, provided that some basic structural requirements are present.

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Section: Metal Complexesmentioning

confidence: 99%

Estrogen Receptor Ligands: A Review (2013–2015)

Farzaneh

Zarghi

2016

Sci. Pharm.

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“…40 Recently, Hanson et al reported the synthesis of the 17αsubstituted estradiol 180 via a Stille coupling reaction 61 between the rhenium complex 179 and the stannylvinyl estradiol 178, the latter being derived from a hydrostannation of ethynyl estradiol 75 (Scheme 50). 100 The coupling reaction between 178 and 5-bromo-2,2′bipyridine remained unsuccessful, and the prechelated Re compound 179 was found to be a good alternative owing to the beneficial electron-withdrawing effect of the metal in such a reaction.…”

Section: Tridentate Sxs-type Chelates (X = N O S)mentioning

confidence: 99%

“…Recently, Hanson et al reported the synthesis of the 17α-substituted estradiol 180 via a Stille coupling reaction between the rhenium complex 179 and the stannylvinyl estradiol 178 , the latter being derived from a hydrostannation of ethynyl estradiol 75 (Scheme ) …”

Section: Potential Radiopharmaceuticalsmentioning

confidence: 99%

Synthesis of Transition-Metal Steroid Derivatives

Bideau

Dagorne

2013

Chem. Rev.

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“…That effect should occur at levels below those at which toxicity is generated in normal cells, or non ER-selective cells. The targeting component should not interfere with the therapeutic responses. ,,,− The process by which ER-targeted conjugates should be screened was described in excellent detail by Katzenellenbogen et al These methods include an initial screening through a series of assays to demonstrate its effectiveness as a ligand with high binding affinity for ER, potent efficacy in an appropriate assay, selective activity in ER-dependent but not ER-negative breast cancer cells, that is reversible by exposure to estradiol.…”

Section: Evolution Of Antiestrogen–drug Conjugatesmentioning

confidence: 99%

Targeting the Estrogen Receptor using Steroid–Therapeutic Drug Conjugates (Hybrids)

Dao

Hanson

2012

Bioconjugate Chem.

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The estrogen receptor (ER) is a potentially useful biological target for diagnosis and therapy in hormonally responsive human breast cancer. This protein is often overexpressed both on the membrane and on the nuclear compartment of breast cancer cells and therefore provides a mechanism for targeted drug delivery. Over the past 30 years, many research groups have attempted to exploit the high affinity and receptor selectivity of steroidal estrogens to deliver cytotoxic agents that by themselves lack selectivity. In this review, we describe the strategies and methods employed by those investigators in their efforts to develop steroid-drug conjugates with the goals of enhanced antiproliferative activity and ER-selectivity. In particular, the choices of steroid scaffolds and sites for drug conjugation have evolved as the understanding of role of ER in cell function has expanded. Present knowledge of the mechanism of action for estrogens and antiestrogens helps explain the failure of most efforts to achieve their stated objectives. The review culminates in the description of our program, which has produced the first conjugate that clearly has achieved those goals and provides an approach for developing new agents for future clinical use.

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Targeting the estrogen receptor with metal-carbonyl derivatives of estradiol

Cited by 10 publications

References 52 publications

Estrogen Receptor Ligands: A Review (2013–2015)

Estrogen Receptor Ligands: A Review (2013–2015)

Synthesis of Transition-Metal Steroid Derivatives

Targeting the Estrogen Receptor using Steroid–Therapeutic Drug Conjugates (Hybrids)

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