University of Missouri

The Dow Chemical Company

Wynn A Volkert

Kattesh V Katti

Jaime Simon

David A Wilson

Alan R Ketring

David E Troutner

Timothy J Hoffman

William F Goeckeler

Douglas E Berning

Gary Sieckman

Ning Li

Hariprasad Gali

Prahlad R Singh

Srinivasa Rao Karra

C Jeffrey Smith

Chrys-Ann Higginbotham

Druce K Crump

Joseph R Garlich

Kavita K Katti

Charles Jeffrey Smith

Robert Churchill

Davis A Wilson

Kandikere R Prabhu

V Sreenivasa Reddy

Nagavara Kishore Pillarsetty

C A Higginbotham

A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

Gastrin receptor-avid peptide conjugates

A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a-moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

There is provided a complex for use as a therapeutic pharmaceutical, the complex has a ligand containing at least one hydroxyalkyl phosphine donor group bound to a gold atom to form a stable gold-ligand complex. Also provided is a method of treating cancer by administering an effective amount of a complex having a ligand of at least one hydroxyalkyl phosphine group bound to a gold atom to form a stable gold-ligand complex. Also provided is a method of preventing the metastasis of cancer and arresting cell growth by administering an effective amount of a complex having a ligand of at least one hydroxyalkyl phosphine group bound to a gold atom to form a stable gold-ligand complex.

Gold-containing chemotherapeutic agents

This invention describes a novel strategy to produce phosphine-functionalized biomolecules (e.g. peptides or proteins) for potential use in the design and development of site-specific radiopharmaceuticals for diagnosis or therapy of specific cancers. Hydrophilic alkyl phosphines, in general, tend to be oxidatively unstable. Therefore, incorporation of such phosphine functionalities on peptide (and other biomolecule) backbones, without oxidizing the P centers, is difficult. In this context this discovery reports on a new technology by which phosphines, in the form of bifunctional chelating agents, can be directly incorporated on biomolecular backbones using manual synthetic or solid phase peptide synthesis methodologies. The superior ligating abilities of phosphine ligands, with various diagnostically (e.g. TC-99m) or therapeutically (e.g. Re186/188, Rh-105, Au-199) useful radiometals, coupled with the findings that the resulting complexes demonstrate high in vivo stability makes this approach useful in the development of radiolabeled biomolecules for applications in the design of tumor-specific radiopharmaceuticals.

Biomolecule conjugation strategy using novel water-soluble phosphine-based chelating agents

There is provided a method of labeling a biomolecule with a transition metal or radiometal in a site specific manner to produce a diagnostic or therapeutic pharmaceutical compound by synthesizing a P N -bifunctional chelating agent intermediate, complexing the intermediate with a radio metal or a transition metal, and covalently linking the resulting metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. Also provided is a method of synthesizing the &mdash;PR containing biomolecules by synthesizing a P N -bifunctional chelating agent intermediate, complexing the intermediate with a radiometal or a transition metal, and covalently linking the resulting radio metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. There is provided a therapeutic or diagnostic agent comprising a &mdash;PR containing biomolecule.

Bifunctional chelating agent for the design and development of site specific radiopharmaceuticals and biomolecule conjugation strategy

A compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical comprises at least one functionalized hydroxyalkyl phosphine donor group and one or more sulfur or nitrogen donor and a metal combined with the ligand.

Hydroxymethyl phosphine compounds for use as diagnostic and therapeutic

A method of forming phosphine-amine conjugates includes reacting a hydroxymethyl phosphine group of an amine-free first molecule with at least one free amine group of a second molecule to covalently bond the first molecule with the second molecule through an aminomethyl phosphorus linkage and the conjugates formed thereby.

Conjugate and method for forming aminomethyl phosphorus conjugates

A compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical comprises a functionalized hydroxyalkyl phosphine ligand and a metal combined with the ligand.

Hydroxyalkyl phosphine compounds for use as diagnostic and therapeutic

A complex and method for making same for use as a diagnostic or therapeutic pharmaceutical includes a ligand comprising at least one hydroxyalkyl phosphine donor group bound to a gold atom to form a gold-ligand complex that is stable in aqueous solutions containing oxygen, serum and other body fluids.

Hydroxyalkyl phosphine gold complexes for use as diagnostic and

New multifunctional ligands for potential use in the design therapeutic

A compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical comprises either a phosphorous or germanium core and at least two hydrazine groups forming a ligand for bonding to a metal extending from the phosphorous or germanium core.

Multifunctional ligand for use as a diagnostic or therapeutic

Particle-emitting radionuclides, e.g. Gd-159, Ho-166, Lu-177 and Yb-175, have been complexed with organic aminoalkylenephosphonic acids. These complexes have been found useful in compositions for the therapeutic treatment of calcific tumors or the relief of bone pain in animals.

Growing community of inventors

Columbia, MO, United States of America

Wynn A Volkert