Radionuclide Antibody-Conjugates, a Targeted Therapy Towards Cancer

Kitson, Sean L.; Cuccurullo, Vincenzo; Moody, Thomas S.; Mansi, Luigi

doi:10.2174/1874471011306020001

Cited by 36 publications

(24 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In line with such good premises, 68 Ga-DOTA-Tyr3-octreotate ( 68 Ga-DOTA-TATE) has been proposed as a potential agent for RGS in GEP-NETs [58,59]; however, further studies are still required to assess its role in this field and evaluate its clinical cost/effectiveness, also because of the radiation dose to the surgical staff [50,60,61].…”

Section: Reviewmentioning

confidence: 99%

Radioguided surgery with radiolabeled somatostatin analogs: not only in GEP-NETs

2017

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Reviewmentioning

confidence: 99%

Radioguided surgery with radiolabeled somatostatin analogs: not only in GEP-NETs

2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…They can act as hydrogen bond acceptors and hydrogen bond donors towards cation and anion recognition sites of amino acids [169]. These compounds possess the vital parameters towards the design of antibody-drug conjugates (ADCs) [170] and radionuclide-antibody conjugates (RACs) [171].…”

Section: Squaramide Lead Compoundsmentioning

confidence: 99%

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

Kitson¹

2017

J Diagn Imaging Ther

Self Cite

View full text Add to dashboard Cite

Molecular Metaphors is the application of squaryl building blocks towards creative functional group chemistry to produce lead compounds and imaging agents. This strategy is applied to rational drug design and to various imaging agents that would normally contain conventional functional group chemistry. These, include carboxylic acids, α-amino acids, peptide bonds and phosphonates. Moreover, the squaryl metaphor is a precursor to complex organic molecules involving functional group interchange (FGI) and rearrangements. This article discusses the application of these metaphors in the area of neurochemistry, especially NMDA receptors. An important area of drug design is the inhibition of angiotensin II enzyme by the use of losartan. This commercial drug contains a tetrazole moiety that can be modified using the squaryl group to give a semisquarate derivative. These concepts can extend to the semisquarate of ibuprofen. Moreover, a discussion on peptidomimetics regarding the substitution of the peptide bond for squaramide allows for a change in the biological properties due to modification at the peptide bond. Furthermore, the topic on how squaryl metaphors can be exploited primarily by the central 1,3-hydroxyamide sequence to the generation of a novel class of HIV protease inhibitors. Also, squaryl metaphors can be used to develop potential inhibitors of glutathione and novel anti-migraine drugs. The discussion continues on the design of anticancer drugs: in particular, a novel class of metalloproteases, including phosphonates for semisquaramides, leading to squaryl nucleosides. This review concludes with the application of squaryl metaphors in the design of positron emission tomography (PET) and magnetic resonance imaging (MRI) agents towards theranostics. describe the ability of individual functional chemical groups to mimic other moieties [2,3]. KeywordsErlenmeyer rationalised these concepts and categorised isosteres into atoms, ions and molecules based on the valence level of electrons [4]. A further understanding by Friedman led to the term bioisosterism to include all atoms and molecules that fit the broadest definition of isosteres [5]. This approach was independent of whether the drug was an agonist or an antagonist towards biological activity.Moreover, Thornber applied the term bioisosterism to include subunits, groups or molecules that possess physicochemical properties of similar biological effects [6]. Finally, in 1991 Burger widened the definition of bioisosteres to include compounds or groups that possess similar molecular shapes and volumes independent of agonists or antagonists [7]. REVIEW ARTICLE Squaryl KitsonThese bioisosteres would require approximately the same distribution of electrons and give a high probability of generating comparable physical properties such as hydrophobicity [8]. Currently, bioisosterism is one of the most useful tools to the medicinal chemist in rational drug design and in particular regarding the carboxylic acid bioisosteres [9]. The carboxylic acid functional ...

show abstract

“…The first category is referred to as radionuclide antibody conjugates (RACs), where a radionuclide emitting radiation penetrates into the targeted cells of the solid tumor to induce a sufficient lethal response with no or minimal damage to the surrounding healthy cells. Initially, there were two approved RACs, namely 131 I-tositumomab (Bexxar) and 90 Y-ibritumomab (Zevalin) used in treatment of B cell lymphoma, HL, NHL, or multiple myeloma (Kitson et al 2013). Bexxar was a mouse IgG2a anti-CD20 mAb labelled with I-131 which emitted both beta and gamma radiations with a half-life of approximately eight days.…”

Section: Payload Selectionmentioning

confidence: 99%

Antibody drug conjugates

Bakhtiar

2016

Biotechnol Lett

View full text Add to dashboard Cite

Antibody drug conjugates (ADCs) have emerged as a viable option in targeted delivery of highly potent cytotoxic drugs in treatment of solid tumors. At the time of writing, only two ADCs have received regulatory approval with >40 others in clinical development. The first generation ADCs suffered from a lack of specificity in amino acid site-conjugations, yielding statistically heterogeneous stoichiometric ratios of drug molecules per antibody molecule. For the second generation ADCs, however, site-specific amino acid conjugation using enzymatic ligation, introduction of unnatural amino acids, and site-specific protein engineering hold promise to alleviate some of the current technical limitations. The rapid progress in technology platforms and antibody engineering has introduced novel linkers, site-specific conjugation chemistry, and new payload candidates that could possibly be exploited in the context of ADCs. A search using the Clinical Trial Database registry ( www.clinicaltrials.gov ), using the keyword 'antibody drug conjugate', yielded ~270 hits. The main focus of this article is to present a brief overview of the recent developments and current challenges related to ADC development.

show abstract

Radionuclide Antibody-Conjugates, a Targeted Therapy Towards Cancer

Cited by 36 publications

References 82 publications

Radioguided surgery with radiolabeled somatostatin analogs: not only in GEP-NETs

Radioguided surgery with radiolabeled somatostatin analogs: not only in GEP-NETs

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

Antibody drug conjugates

Contact Info

Product

Resources

About