Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene

Huang, Qiaoxian; Zhao, Hong; Shui, Mingju; Guo, Dong‐Sheng; Wang, Ruibing

doi:10.1039/d0sc03922e

Cited by 43 publications

(39 citation statements)

References 48 publications

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“…Unfractionated heparin (UFH) is widely used in clinical practice as an anticoagulant agent. However, when overdosed or administered in sensitive populations, UFH may cause several side effects including excessive bleeding 40 . The only clinically available UFH neutralization agent, protamine, has several risks as well associated with its use, including allergic reactions in a large sub-population of patients 40 .…”

Section: Calixarenesmentioning

confidence: 99%

“…However, when overdosed or administered in sensitive populations, UFH may cause several side effects including excessive bleeding 40 . The only clinically available UFH neutralization agent, protamine, has several risks as well associated with its use, including allergic reactions in a large sub-population of patients 40 . Hence, it is essential to develop novel UFH neutralizers to reverse heparinization in an effective and safe manner, as a replacement or supplementary of protamine.…”

Section: Calixarenesmentioning

confidence: 99%

“…Very recently, a biocompatible oligoethylene glycol functionalized guanidinecalixarene (GC[4]AOEG), which binds with UFH with a high binding affinity (10 7 M -1 ), was designed as a supramolecular antidote against UFH. In vivo tests in three mouse bleeding models showed that GC[4]AOEG can effectively alleviate excessive bleeding induced by UFH with an excellent safety profile, indicating a great potential of GC[4]AOEG for clinical translation as a UFH neutralizer 40 .…”

Section: Calixarenesmentioning

confidence: 99%

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Recent advances in supramolecular antidotes

Yin¹,

Zhang²,

Wei³

et al. 2021

Theranostics

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Poisons always have fascinated humankind. Initially considered as deleterious or hazardous substances, the modern era has witnessed the controlled utilization of dangerous poisons in medicine and cosmetics. Simultaneously, antidotes have become crucial as reversal agents to counteract the effects of a poison, and they are also used today to positively cancel the benefits of a poison after use. Currently, the majority of poisons are composed of small molecules. This review focuses on recent developments to reverse or prevent toxic effects of poisons by encapsulation in host molecules. Cyclodextrins, cucurbiturils, acyclic cucurbituril derivatives, calixarenes, and pillararenes, have been reported to largely impact the effects of toxic compounds, thus extending the current paradigm of small molecule antidotes by adding a new family of macrocyclic compounds to the current arsenal of antidotes. Along this line of research, endogenous "harmful" species are also sequestered by one or more of these supramolecular host molecules, expanding the potential of supramolecular antidotes to diverse therapeutic areas.

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Section: Calixarenesmentioning

confidence: 99%

Section: Calixarenesmentioning

confidence: 99%

Section: Calixarenesmentioning

confidence: 99%

See 1 more Smart Citation

Recent advances in supramolecular antidotes

Yin¹,

Zhang²,

Wei³

et al. 2021

Theranostics

Self Cite

View full text Add to dashboard Cite

show abstract

“…More recently, an oligoethylene glycol functionalized, positively-charged guanidinocalixarene (GC[4]AOEG) was prepared in an attempt to neutralize the toxicity of unfractionated heparin (UFH) [5]. UFH is clinically used as an anticoagulant agent, but when administered in sensitive populations or overdosed, UFH can decrease blood pressure and slow heart rate, potentially causing internal bleeding.…”

Section: Calix[n]arenes (C[n]mentioning

confidence: 99%

“…GC [4]AOEG was shown to effectively reverse UFH-induced excessive bleeding of several external and internal injuries in mice, with no adverse effects observed, highlighting its significant potential for clinical translation. and two decades since the other key members of the cucurbiturils (e.g., CB [5], CB [7], and CB [8]) were discovered from the same synthetic approach. However, it was not until 2015 that CB [7] was found to reverse anesthesia in zebrafish induced by the FDA approved veterinary drug tricaine mesylate via supramolecular capture (Figure 2) [6].…”

Section: Calix[n]arenes (C[n]mentioning

confidence: 99%

Macrocycles and Related Hosts as Supramolecular Antidotes

Yin

Bardelang

Wang

2021

Trends in Chemistry

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Broad‐Spectrum Detoxification of Snake Venoms With Supramolecular Materials Integrated via Molecular Recognition and Coassembly

Chen,

Tian,

Cheng

et al. 2024

Adv Healthcare Materials

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Snakebite is a medical emergency that often leads to high mortality and morbidity in tropical and subtropical regions. The diversity in venom composition between various types of snakes necessitates the use of different specific antivenom treatments, which presents clinical and financial challenges in the management of snakebites. Therefore, developing a broad‐spectrum antidote to neutralize complex and diverse snake venoms has assumed critical importance. Herein, a broad‐spectrum antidote is developed through molecular recognition and coassembly to neutralize four kinds of snake venom toxins, those are three‐finger toxin (3FTx), snake venom metalloproteinase (SVMP), phospholipase A2 (PLA2), and snake venom serine protease (SVSP), which have high abundance and toxicity. The coassembly of sulfonate‐modified amphiphilic calixarene (SCA) and amphiphilic cyclodextrin (CD) is employed to neutralize the toxicity of 3FTx, 1,2‐dodecanedithiol (DDT) and thioetheramide phosphorylcholine (TEAPC) are introduced through coassembly to neutralize toxicity of SVMP and PLA2, respectively, and the nafamostat (NT), which can be loaded through the host‐guest complexation, is employed to neutralize toxicity of SVSP. The broad‐spectrum antidote, NT@SCA/CD/DDT/TEAPC, effectively neutralizes key toxins from the most medically important cobra and vipers, significantly improving survival rates of poisoned mice. This study conceptually validated the feasibility of broad‐spectrum detoxification and also offers a conveniently integrated supramolecular strategy.

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Heparin reversal by an oligoethylene glycol functionalized guanidinocalixarene

Abstract: An oligoethylene glycol functionalized guanidinocalix[4]arene was developed as a safe antidote against heparin, via specific recognition and neutralization of heparin in vitro and in vivo.

Cited by 43 publications

References 48 publications

Recent advances in supramolecular antidotes

Recent advances in supramolecular antidotes

Macrocycles and Related Hosts as Supramolecular Antidotes

Broad‐Spectrum Detoxification of Snake Venoms With Supramolecular Materials Integrated via Molecular Recognition and Coassembly

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