The Synthesis of Cryptophycins.

Eissler, Stefan; Stoncius, Arvydas; Nahrwold, Markus; Sewald, Norbert

doi:10.1002/chin.200706258

Cited by 7 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cryptophycins display a very high cytotoxicity (typically in the low picomolar range) on a broad variety of cancer cells, including multidrug-resistant ones . Initial studies focused on the total synthesis and application of cryptophycins as traditional chemotherapeutics, but disappointing results in monotherapy phase II clinical trials prompted a focus shift toward ligand-based pharmacodelivery approaches. , However, the parental compound lacks an addressable functional group for the conjugation to a homing device. Therefore, research has been focused on the generation of cryptophycin derivatives that can be conjugated and subsequently released, preserving the potent cytotoxicity of the parent compound. − …”

Section: Introductionmentioning

confidence: 99%

In Vivo Antitumor Activity of a Novel Acetazolamide–Cryptophycin Conjugate for the Treatment of Renal Cell Carcinomas

et al. 2018

Self Cite

View full text Add to dashboard Cite

Traditional chemotherapeutics used in cancer therapy do not preferentially accumulate in tumor tissues. The conjugation to delivery vehicles like antibodies or small molecules has been proposed as a strategy to increase the tumor uptake and improve the therapeutic window of these drugs. Here, we report the synthesis and the biological evaluation of a novel small molecule–drug conjugate (SMDC) comprising a high-affinity bidentate acetazolamide derivative, targeting carbonic anhydrase IX (CAIX), and cryptophycin, a potent microtubule destabilizer. The biological activity of the novel SMDC was evaluated in vitro, measuring binding to the CAIX antigen by surface plasmon resonance and cytotoxicity against SKRC-52 cells. In vivo studies showed a delayed growth of tumors in nude mice bearing SKRC-52 renal cell carcinomas.

show abstract

Section: Introductionmentioning

confidence: 99%

In Vivo Antitumor Activity of a Novel Acetazolamide–Cryptophycin Conjugate for the Treatment of Renal Cell Carcinomas

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Initially, a Cryptophycin-52 synthetic analog was designed but, unfortunately, due to a lack of efficacy in vivo combined to the high neurotoxicity, it failed as potential clinical candidate [ 88 ]. A further investigation of structural moieties necessary for biological activity permitted to develop large number of synthetic analogues [ 89 , 90 , 91 ] that showed excellent antitumor activity (picomolar level) against mammary, colon, and pancreatic adenocarcinomas in mouse xenographs.…”

Section: Antimitotic Drugsmentioning

confidence: 99%

Molecular Delivery of Cytotoxic Agents via Integrin Activation

Cirillo

Giacomini

2021

Cancers

View full text Add to dashboard Cite

Integrins are cell adhesion receptors overexpressed in tumor cells. A direct inhibition of integrins was investigated, but the best inhibitors performed poorly in clinical trials. A gained attention towards these receptors arouse because they could be target for a selective transport of cytotoxic agents. Several active-targeting systems have been developed to use integrins as a selective cell entrance for some antitumor agents. The aim of this review paper is to report on the most recent results on covalent conjugates between integrin ligands and antitumor drugs. Cytotoxic drugs thus conjugated through specific linker to integrin ligands, mainly RGD peptides, demonstrated that the covalent conjugates were more selective against tumor cells and hopefully with fewer side effects than the free drugs.

show abstract

“…Some years later, researchers at the University of Hawaii reisolated cryptophycins from a different Nostoc strain and discovered that these compounds showed remarkable cytotoxic activity in picomolar concentrations (Trimurtulu et al 1994), representing the most potent suppressors of microtubule dynamics yet described. Detailed structureactivity relationship studies based on semi-synthetic and synthetic derivatives of the natural cryptophycins have been conducted (Eggen and Georg 2002;Eißler et al 2006). In addition, they are not effective substrates of the P-glycoprotein and thus remain active against multidrug-resistant cancer cells .…”

Section: Cryptophycins As Leads For Anti-cancer Drugsmentioning

confidence: 99%