Nimbus Iris, Inc.

Anadys Pharmaceuticals, Inc.

Alan Franklin Corin

Craig E Masse

Jeremy Robert Greenwood

Donna Lee Romero

Geraldine C Harriman

Leah Lynn Frye

Mee Shelley

Shaughnessy Robinson

Matthew David Wessel

Karl Shawn Watts

Andrew A Pakula

Julianne Bryan

The present invention provides 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine compounds and pharmaceutical compositions thereof as inhibitors of IRAK.

IRAK inhibitors and uses thereof

The present invention provides thienopyrimidine and thienopyridine compounds, compositions thereof, and methods of using the same for the treatment of diseases mediated by IRAK enzymes. Such diseases include inflammatory and proliferative diseases.

The present invention is directed to a method for selecting compounds for use in treating sickle cell disease in a patient. The method comprises the steps of selecting a first set of HbS ligands from a first group of chemical compounds, selecting from the first set of HbS ligands a seconds set that exhibit inhibition of HbS polymerization, and selecting from the second set a third set that display anti-sickling activity of red blood cells when in the presence thereof. The method may include the step of performing a methemoglobin S proteolysis assay measuring a percent protease protection for each compound. The method may additionally include the steps of measuring HbS aggregation, inhibition of protease, deoxy-HbS gelation inhibition activity, O,affinity of HbS, and cytotoxic effect to cell activity. The method may further include assessing red blood cell morphology, and eliminating compounds that contain moieties that bind to heme. The steps of the method may be repeated on analogs of compounds that are selected using one or more steps of the method. The present invention also includes a method of treating sickle cell disease in a patient, which comprises administering to the patient a pharmaceutical formulation including a selected concentration of an HbS ligand and a pharmaceutically acceptable carrier therefore. The HbS ligand, which may be an isoquinolium derivative, is one exhibiting inhibition of HbS polymerization and displaying anti-sickling activity of red blood cells when in the presence thereof.

Anti-sickling agents: selection methods and effective compounds

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Sudbury, MA, United States of America

Alan Franklin Corin