National Institutes of Health, a Component of the US Dept. of Health & Human Services

University System of Maryland

The United States of America As Represented by the Department of Health

The United States Government As Represented by the Department of Veterans Affairs

The United States of America As Represented by the Secretary of

Christopher J Michejda

Nadya Tarasova

Jeffrey J Blumenstein

Zoltan Szekely

Susan K Keay

Marek W Cholody

William G Rice

Marshall Morningstar

Wieslaw Marek Cholody

Thomas P Conrads

Stephen Oroszlan

Timothy D Veenstra

James A Turpin

Terry D Copeland

Sergey G Tarasov

Thomas Roth

Michael M Gottesman

Vadim Gaponenko

Alan O Perantoni

Maria Michejda, Legal Representative

Christine A Hrycyna

Marcin Dyba

Humcha Krishnamurthy Hariprakasha

Teresa Kosakowska-Cholody

Piotr Kaczmarek

Olga Timofeeva

Lidia Hernandez

Gillian Tocci

Brian Lewis Hood

A peptide or peptidomimetic comprising the amino acid sequence of the second helix of a STAT protein, or a variant of such sequence, wherein the peptide or peptidomimetic comprises about 40 or fewer amino acids and binds to a STAT protein, as well as a method of inhibiting a STAT protein in a cell, a method of treating or preventing a disease associated with STAT overexpression in a host, and related compounds, compositions, and methods.

Peptide-based stat inhibitor

The invention provides a method of handling a hydrophobic agent, which method comprises (a) combining in an aqueous solution (i) a hydrophobic agent and (ii) an isolated peptide that is a structural analog of a transmembrane domain of an integral membrane protein, wherein one terminus of the peptide has one or more negatively charged residues, and (b) allowing the peptide to self-assemble into nanoparticles, wherein the nanoparticles comprise the hydrophobic agent.

Self-assembling nanoparticles composed of transmembrane peptides and their application for specific intra-tumor delivery of anti-cancer drugs

A novel antiproliferative factor comprising a glycopeptide is disclosed. In specific embodiments, the novel antiproliferative factor is associated with the bladder. Compositions, diagnostic kits and reagents, and methods of using the compounds for identifying and/or treating interstitial cystitis and cancer are disclosed.

Antiproliferative factor and methods of use

Derivatives of a novel antiproliferative factor comprising a glycopeptide is disclosed. In specific embodiments, the novel antiproliferative factor is associated with the bladder. Compositions, diagnostic kits and reagents, and methods of using the compounds for identifying and/or treating interstitial cystitis and cancer are disclosed. In particular embodiments, the glycopeptide comprises D-proline.

Derivatives of APF and methods of use

Derivatives of bladder epithelial antiproliferative factor and methods of using them are disclosed. In specific embodiments, the glycopeptide compositions are useful for the treatment and/or prevention of medical conditions, including cancer. In other embodiments, there are compositions and methods related to treatment of bladder conditions. In particular embodiments, the glycopeptide comprises D-pipecolic acid or L-pipecolic acid.

An azonafide-based compound of Formula I, a composition comprising the compound, and a method of using the compound to deliver a cytotoxic azonafide derivative to a cell, as well as related compounds and methods for the use thereof to pre-pare an azonafide-based compound of Formula I. 

Azonafide derived tumor and cancer targeting compounds

A conjugate of formula: V&#x2014;(Y)&#x2014;Z-T: (I), T-X&#x2014;B&#x2014;(Y)&#x2014;Z-T': (II), V&#x2014;(Y)Z&#x2014;(Y&#x2032;)V&#x2032;: (III), T-X&#x2014;B&#x2014;(Y)&#x2014;Z&#x2014;(Y&#x2032;)&#x2014;X&#x2032;&#x2014;B&#x2032;-T&#x2032;: (IV), V&#x2014;(Y)&#x2014;Z&#x2014;(Y&#x2032;)&#x2014;X&#x2014;B-T: (V), V&#x2014;(Y)&#x2014;Z&#x2014;X&#x2014;B&#x2014;Z&#x2032;&#x2014;(Y&#x2032;)&#x2014;(V&#x2032;): (VI), or (W)&#x2014;(Y)&#x2014;[(Z)&#x2014;(Y&#x2032;)&#x2014;(X&#x2014;B)&#x2014;(Y&#x2033;)&#x2014;(Z&#x2032;)]&#x2014;(Y . . . )&#x2014;(W&#x2032;): (VII), in which W and W&#x2032; are independently a DNA intercalator or terminal subunit, V and V&#x2032; are independently a DNA intercalator, X and X&#x2032; are independently a DNA alkylator, B and B&#x2032; are the same or different and each is a heteoaromatic residue that is attached to the Nterminus of an alkylator subunit (X or X&#x2032;), Y, Y&#x2032;, Y&#x2033; and Y&#x2032;&#x2033; are independently a linker, T and T&#x2032; are independently terminal subunits, Z and Z&#x2032; are independently a polyamide group that binds to the minor groove of DNA, a, b, c, d, f, g, i, and j are independently 0 to 5, and e and h are independently 1 to 5, a composition comprising a conjugate of any of formulae (I)-(VII) and a carrier, and a method for treating cancer in a mammal comprising administering an effective amount of a conjugate of any of formulae (I)-(VII) or a composition comprising same.

DNA-binding polyamide drug conjugates

ATP-binding cassette (ABC) transporters generally contain a number of transmembrane helices. The present invention provides synthetic peptides derived from these transmembrane helices. The peptides inhibit ABC transporter function, presumably by disrupting the structure of the ABC transporter. Negatively charged residues are added at the extracellular terminus to promote correct orientation of the peptide in the membrane, and residues considered to aid solubility may be added at that terminus to increase solubility. Exemplary ABC transporters that can be inhibited by these peptides include MDR1, MRP1, MRP2 and BCRP. The invention further provides nucleic acids encoding the peptides, expression cassettes comprising the nucleic acids, and host cells expressing the expression cassettes. The invention further provides a simple and inexpensive assay for determining whether a potential chemotherapeutic agent can inhibit the activity of P-gly-coprotein.

Inhibition of ABC transporters by transmembrane domain analogs

G-protein coupled receptors (GPCR) generally contain seven transmembrane helices. The present invention provides synthetic peptides derived from these transmembrane helices. The peptides inhibit GPCR function by disrupting GPCR structure. In certain embodiments, charged residues are added at one terminus to promote correct orientation of the peptide in the membrane.

G protein-coupled receptor antagonists

The present invention provides compositions and methods for the treatment of HIV infection. In particular, the present invention provides non-nucleoside inhibitors of reverse transcriptase (RT), as well as methods to treat HIV infection using these non-nucleoside inhibitors of RT. In preferred embodiments, the present invention provides a novel class of substituted benzimidazoles, effective in the inhibition of human immunodeficiency virus (HIV) RT.

Substituted benzimidazoles as non-nucleoside inhibitors of reverse transcriptase

The invention provides imidazoacridone compounds of general formula (1) which have cytotoxic and anti-tumor activity. The invention also provides methods of preparing the compounds, and methods of using the compounds for the treatment of cancer or other mammalian diseases characterized by undesirably high levels of cell proliferation. The compounds of the invention are also expected to have utility as research tools.

1,8-naphthalimide imidazo&lcub;4,5,1-de&rcub;acridones with anti-tumor activity

Acridone-derived compounds useful as antineoplastic and antiretroviral agents

Substituted benzimidazoles, and methods of use thereof, for the inhibition of HIV reverse transcription and for the treatment of HIV infection

The present invention relates to several novel acridone-derived compounds of of formula (I) or (II). These compounds are potent anti-viral agents, useful in the treatment of viral diseases, such as Human Immunodeficiency Virus. In addition, these compounds are anti-neoplastic agents useful in the treatment of various forms of cancer.

Growing community of inventors

North Potomac, MD, United States of America

Christopher J Michejda