University of Illinois

Sfunga Therapeutics, Inc.

University of Iowa Research Foundation

Cystetic Medicines, Inc.

Martin D Burke

Stephen J Davis

Eric P Gillis

David M Knapp

Brice E Uno

Kaitlyn C Gray

Pulin Wang

Stephen Scott Davis

Justin Robert Struble

Ian Dailey

Nagarjuna Palyam

Junqi Li

Zachary Kevin Sweeney

Elena S Koltun

Kevin T Mellem

Arun P Thottumkara

Graham R Dick

Jenna A Klubnick

Paul Joseph Hergenrother

Timothy M Fan

Fadi G Alnaji

Katrina A Muraglia

Anna SantaMaria

Christopher B Brooke

Leyi Wang

Kelsie J Green

Robin L Holland

Diana Rose Ranoa

Anthony S Grillo

Steven G Ballmer

Ian Crouch

Souvik Rakshit

Jeffry G Weers

Michael J Welsh

Jennifer Hou

Agnieszka Lewandowska

Corinne Soutar

Thomas Tarara

Rajeev S Chorghade

Daniel Blair

Alexander G Cioffi

Andrew Blake

Greg Morehouse

Anuj Khandelwal

Jiabao Zhang

Jonathan Lehmann

Andrea Palazzolo

Claire Simons

Robert W Pipal

Michael Schmidt

Suk Joong Lee

Arun Maji

Zachary K Sweeney

Katrina A Diaz

Disclosed are pharmaceutical compositions, comprising: (i) amphotericin B or a pharmaceutically acceptable salt or hydrate thereof; (ii) cholesterol; (iii) phospholipids, comprising hydrogenated soy phosphatidylcholine and distearoylphosphatidylglycerol; and (iv) calcium chloride (CaCl)). Also disclosed are methods of using the pharmaceutical compositions for treating a disease or disorder (e.g., cystic fibrosis), increasing the pH of airway surface liquid, increasing bicarbonate secretion into airway surface liquid, and increasing a subject's forced expiratory volume in one second.

Ion channel prosthetic compositions comprising lipid-coated crystals of amphotericin B

Disclosed are methods of treating cystic fibrosis using AmB and a sterol or compositions comprising AmB and a sterol. Also disclosed are methods of increasing the pH of airway surface liquid in a patient having cystic fibrosis using AmB and a sterol; and methods of decreasing the viscosity of airway surface liquid in a patient having cystic fibrosis using AmB and a sterol.

Genotype-agnostic rescue of cystic fibrosis with small molecule bicarbonate channels

Disclosed are analogues of hinokitiol, methods for preparing them, and pharmaceutical compositions thereof. Also disclosed are methods for their use in treating iron-related diseases.

Hinokitiol analogues, methods of preparing and pharmaceutical compositions thereof

Provided are certain derivatives of amphotericin B (AmB) characterized by reduced toxicity and retained anti-fungal activity. Certain of the derivatives are C16 urea derivatives of AmB. Certain of the derivatives are C3, C5, C8, C9, C11, C13, or C15 deoxy derivatives of AmB. Certain of the derivatives include C3′ or C4′ modifications of the mycosamine appendage of AmB. Also provided are methods of making AmB derivatives of the invention, pharmaceutical compositions comprising AmB derivatives of the invention, and methods of use of AmB derivatives of the invention.

Amphotericin B derivatives with improved therapeutic index

A saliva-based testing method that bypasses the need for RNA isolation/purification is described herein. In experiments with inactivated SARS-CoV-2 virus spiked into saliva, this method has a limit of detection of 500-1000 viral particles per mL, rivalling the standard NP swab method. Initial studies showed excellent performance with 100 clinical samples. This saliva-based process is operationally simple, utilizes readily available materials, and can be easily implemented by existing testing sites thus allowing for high-throughput, rapid, and repeat testing of large populations.

Saliva-based molecular testing for SARS-CoV-2

Provided herein are complexes comprising amphotericin B (AmB) or derivatives and sterols. Also provided herein are methods of treating cystic fibrosis using AmB or complexes comprising AmB or derivatives and sterols.

Small molecule-mediated restoration of airway surface physiology in human cystic fibrosis lung epithelia

Provided are methods of treating a disease or condition characterized by a deficiency of or a defect in an iron transporter using a small molecule. For example, the method may increase transepithelial iron transport, or it may increase iron release. Additionally, the small molecule may be hinokitiol, or it may be selected from the group consisting of amphotericin B, calcimycin, nonactin, deferiprone, purpurogallin, and maltol. Also provided is a method of identifying a compound capable of treating a disease or condition characterized by a deficiency of or a defect in an iron transporter.

Restoring physiology in iron-deficient organisms using small molecules

Disclosed are derivatives of amphotericin B (AmB) characterized by improved clinical efficacy with reduced toxicity compared to AmB. Also disclosed are pharmaceutical compositions comprising the AmB derivatives, therapeutic methods of using the AmB derivatives and methods of making the AmB derivatives.

Hybrid Amphotericin B derivatives with reduced toxicity

Provided are certain derivatives of amphotericin B (AmB) characterized by reduced toxicity and retained anti-fungal activity. Certain of the derivatives are C16 urea derivatives of AmB. Certain of the derivatives are C3, C5, C8, C9, C11, C13, or C15 deoxy derivatives of AmB. Certain of the derivatives include C3' or C4&#x2032; modifications of the mycosamine appendage of AmB. Also provided are methods of making AmB derivatives of the invention, pharmaceutical compositions comprising AmB derivatives of the invention, and methods of use of AmB derivatives of the invention.

Disclosed are derivatives of amphotericin B (AmB) characterized by improved therapeutic index compared to AmB. The AmB derivatives include C16 ureas, carbamates, and amides according to Formula (I); C3'-substituted C16 ureas, carbamates, and amides according to Formula (II); C16 acyls according to Formula (III); C2&#x2032;epi-C16 ureas, carbamates, and amides according to Formula (IV); and C16 oxazolidinone derivatives according to Formula (V). Also disclosed are pharmaceutical compositions comprising the AmB derivatives, and therapeutic methods of using the AmB derivatives.

Derivatives of amphotericin B

Disclosed are a range of protected organoboronic acid reagents useful in the modular assembly of complex organic compounds. The reactivities of the protected organoboronic acid reagents may be varied predictably by changes to the number and identities of their substituents. Also disclosed are methods of using the protected organoboronic acid reagents in the synthesis of organic compounds.

Protected organoboronic acids with tunable reactivity, and methods of use thereof

Provided are methods for making and using chiral, non-racemic protected organoboronic acids, including pinene-derived iminodiacetic acid (PIDA) boronates, to direct and enable stereoselective synthesis of organic molecules. Also provided are methods for purifying PIDA boronates from solution. Also provided are methods for deprotection of boronic acids from their PIDA ligands. The purification and deprotection methods may be used in conjunction with methods for coupling or otherwise reacting boronic acids. Iterative cycles of deprotection, coupling, and purification can be performed to synthesize chiral, non-racemic compounds. The methods are suitable for use in an automated chemical synthesis process. Also provided is an automated small molecule synthesizer apparatus for performing automated stereoselective synthesis of chiral, non-racemic small molecules using iterative cycles of deprotection, coupling, and purification.

Automated synthesis of small molecules using chiral, non-racemic boronates

Disclosed is a simplified, readily scalable series of individual methods that collectively constitute a method for the synthesis of C2'epiAmB, an efficacious and reduced-toxicity derivative of amphotericin B (AmB), beginning from AmB. Also provided are various compounds corresponding to intermediates in accordance with the series of methods. 

Scalable synthesis of reduced toxicity derivative of amphotericin B

Growing community of inventors

Champaign, IL, United States of America

Martin D Burke