Calicheamicins, a novel family of antitumor antibiotics. 4. Structure elucidation of calicheamicins .beta.1Br, .gamma.1Br, .alpha.2I, .alpha.3I, .beta.1I, .gamma.1I, and .delta.1I

Lee, May D.; Dunne, T. S.; Chang, Ching‐Fong; Siegel, Marshall M.; Morton, George O.; Ellestad, George A.; McGahren, William J.; Borders, Donald B.

doi:10.1021/ja00029a030

Cited by 126 publications

(49 citation statements)

References 2 publications

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“…Inotuzumab ozogamicin (INO; CMC-544) was designed to take advantage of these properties, combining a humanized immunoglobulin G4 anti-CD22 antibody (G544) with the cytotoxic antibiotic calicheamicin. [4][5][6][7] Internalization of CD22 allows for the release of calicheamicin to induce apoptosis. 3,8,9 A phase I monotherapy study 10 established the maximum-tolerated dose (MTD) of INO (1.8 mg/m 2 every 4 weeks), reported reversible thrombocytopenia as the main toxicity, and demonstrated preliminary activity in heavily pretreated patients…”

Section: Introductionmentioning

confidence: 99%

Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab

Fayad

Offner

Smith

et al. 2013

JCO

141

105

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A B S T R A C T PurposeInotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20 ϩ / CD22 ϩ B-cell non-Hodgkin lymphoma (NHL). Patients and MethodsA dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles. ResultsIn all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m 2 ) was confirmed to be the same as that for single-agent INO (1.8 mg/m 2 ). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n ϭ 39), relapsed DLBCL (n ϭ 42), and refractory aggressive NHL (n ϭ 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. ConclusionR-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20 ϩ / CD22 ϩ B-cell NHL.

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Section: Introductionmentioning

confidence: 99%

Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab

Fayad

Offner

Smith

et al. 2013

JCO

141

105

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“…To date, at least twelve members of this family of antibiotics have been discovered [255], all of which fall roughly in two categories. The members of the first category of enediynes are classified as chromoprotein enediynes because they possess a 9-membered ring chromophore core structure, which also requires a specific associated protein for chromophore stabilization.…”

Section: Enediyne Antibioticsmentioning

confidence: 99%

Pharmacologically Active Sulfur-Containing Compounds

Řezanka¹,

Sobotka²,

Spížek³

et al. 2006

AIAMC

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In addition to sulfur-containing compounds that form essential and indispensable constituents of all living cells, there is a plethora of less wide-spread sulfur-containing compounds with much less common and often unexpected properties, chemical structures and biological activities. Some of these compounds have long been known as efficient antibiotics. This review surveys these less known compounds with two and more sulfur atoms in their molecule. In particular, it deals with natural heterocyclic compounds isolated, e.g., from bacteria, fungi, lichens, plants, and animals but also from unusual and exotic sources such as sea invertebrates (coelenterates, sponges, tunicates, sea worms), etc. Compounds such as calicheamicins, thiazole-related compounds and epipolythiodioxopiperazines may serve as examples. Because of their vast variety, individual compounds are grouped according to their chemical structure (only compounds whose chemical structure has been identified are included). These compounds affect a huge array of organisms from microorganisms to man, and the pharmacological activities they exert range from antiviral, antibacterial, antifungal, insecticidal or antiprotozoan effects to regulation of gene expression, cytoskeleton disruption, immunomodulation, plant growth stimulation or inhibition, pro-or antioxidant action, effects on selected enzymes, receptors and signal transduction pathways, etc. The activities are however often known only sketchily, and this paucity of data, and the fact that the activities were tested on a diverse spectrum of test organisms, cell lines, etc., is of necessity reflected in our survey. Two seemingly trivial but important points deserve attention: (a) compounds with widely different structures and from widely different sources have often very similar pharmacological effects; (b) a slight modification in the molecule may bring vast changes in the biological effects of the compound, in terms of quality, quantity and targeting. The purpose of the review was to show both the unique and common features of these compounds and to point out their potential usefulness for mankind.

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“…While this functional group is not typically common in naturally-occurring metabolites, two members of the enediyne antitumor antibiotics (calicheamicin and esperamicin) 67,68 contain a rare N , O -disaccharide bond that contributes to their ability to bind DNA. To explore the potential of this natural neoglycoside handle, two calicheamicin variants, the trisaccharide-containing α 3 I and its N -acetyl analog, were tested as aglycons in single-step neoglycosylation reactions with D-ribose in methanol using an equivalent of acetic acid.…”

Section: Section 4 – Natural Product and Small Molecule Drug Discovermentioning

confidence: 99%

Neoglycosylation and neoglycorandomization: enabling tools for the discovery of novel glycosylated bioactive probes and early stage leads

Goff

Thorson

2014

Med. Chem. Commun.

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This review focuses upon the development, scope, and utility of the highly versatile chemoselective alkoxyamine-based ‘neoglycosylation’ reaction first described by Peri and Dumy. The fundamentals of neoglycosylation and the subsequent development of a ‘neoglycorandomization’ platform to afford differentially-glycosylated libraries of plant-based natural products, microbial-based natural products, and small molecule-based drugs for drug discovery applications are discussed.

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Calicheamicins, a novel family of antitumor antibiotics. 4. Structure elucidation of calicheamicins .beta.1Br, .gamma.1Br, .alpha.2I, .alpha.3I, .beta.1I, .gamma.1I, and .delta.1I

Cited by 126 publications

References 2 publications

Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab

Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab

Pharmacologically Active Sulfur-Containing Compounds

Neoglycosylation and neoglycorandomization: enabling tools for the discovery of novel glycosylated bioactive probes and early stage leads

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