The United States of America, As Represented by the Secretary, Department of Health and Human Services

Children's National Medical Center

Martin John Schnermann

Roger Rauhauser Nani

Hisataka Kobayashi

Peter Choyke

James Blaine Shaum

Michael Philip Luciano

Megan S Michie

Alexander Patrick Gorka

Kirk R Gustafson

James Brislin McMahon

William Douglas Figg

Paresma R Patel

Peter C W Kim

Jaepyeong Cha

Susanna T S Chan

Venu G Bandi

Heptamethine cyanines for use as fluorescent markers of the biliary and renal systems are disclosed. Certain heptamethine cyanines exhibit renal system specificity, while others exhibit biliary system specificity. The compounds may be used for diagnostic purposes and/or for visualization of renal or biliary systems during surgery.

Heptamethine cyanines for use as fluorescent markers of the biliary and renal systems

This disclosure provides IR700-molecule conjugates and methods of their use to remove (e.g., separate or isolate) a target from a sample in vivo or from a subject in vitro. It is shown herein that exposure of IR700 to near infrared (NIR) light removes a portion of IR700, changing it from a hydrophilic molecule, to one that is hydrophobic, resulting in aggregation of IR700 and anything bound to it. For example, the disclosed IR700-molecule conjugates and methods provide photo-controlled ways to control the pharmacokinetics of a drug in vivo, and can be used to remove undesired agents from environmental or food samples or to isolate target molecules in a laboratory.

Photo-controlled removal of targets in vitro and in vivo

Heptamethine cyanine fluorophore conjugates and conjugate precursors are disclosed. Methods of using the conjugates and conjugate precursors are also disclosed. The disclosed conjugates are neutral zwitterionic molecules and exhibit little or no aggregation.

Non-aggregating heptamethine cyanine fluorophores for in vivo imaging

Conformationally restricted cyanine fluorophores, as well as methods of making and using the compounds, are described. The conformationally restricted cyanine fluorophores have a chemical structure according to Formula I, or a stereoisomer or pharmaceutically acceptable salt thereof: wherein A is and wherein each '*' designates an attachment point of A.

Conformational restriction of cyanine fluorophores in far-red and near-IR range

Cyanine fluorophores including a nine-carbon polymethine bridge are disclosed. The cyanine fluorophores have absorbance and/or emission maxima in the near-infrared (NIR) and short-wave infrared (SWIR) wavelength ranges. Methods of making and using the cyanine fluorophores are also disclosed. The compounds are useful in fluorescence imaging, more particularly in cancer treatment. The compounds have generic formula (I): 

Water soluble novel cyanine fluorophore with tunable properties between near IR and SWIR region for in vivo imaging

Embodiments of C4'-alkyl-ether heptamethine cyanine fluorophores according to general formula I, and pharmaceutically acceptable salts thereof, are disclosed. Methods of making and using the C4&#x2032;-alkyl-ether heptamethine cyanine fluorophores also are disclosed. 

Class of stable heptamethine cyanine fluorophores and biomedical applications thereof

Embodiments of near-infrared light-cleavable heptamethine cyanine-based conjugates, particularly targeting agent-drug conjugates, according to Formula I and conjugate precursors are disclosed. The disclosed targeting agent-drug conjugates are useful for targeted delivery and release of a drug. Methods of making and using the conjugates and precursors also are disclosed. 

Near-IR light-cleavable conjugates and conjugate precursors

Embodiments of small molecule inhibitors of hypoxia inducible factor 1 (HIF-1) and pharmaceutical compositions thereof are disclosed. The disclosed compounds suppress HIF-1 activity by inhibiting the interaction between the HIF-1 &#x3b1; subunit and transcriptional co-activator protein p300. Embodiments of methods for making and using the small molecule inhibitors are also disclosed.

Growing community of inventors

Rockville, MD, United States of America

Martin John Schnermann