Wayne State University

University of California

University of Hawai'i

Advanced Research & Technology Institute

Purdue Research Foundation

Indiana University

Henry Ford Health System

Frederick A Valeriote

Thomas Hughes Corbett

D James Morre

Paul A Grieco

Richard E Moore

Trimurtulu Golakoti

William H Gerwick

Gregory M Patterson

Susan L Mooberry

Charles D Smith

Jian Wen Liang

Marcus A Tius

Phillip Crews

Sheng Lin

Bradley S Moore

Thomas K Hemscheidt

Alban R Pereira-Badilla

Nicholas Lorig-Roach

Tara Byrum

Michael Kenneth Gilson

Russell A Barrow

Karen Tenney

Andrew T Fenley

Andrew Kale

Erin P McCauley

Hosana Debonsi

Kevin Tidgewell

Provided are pyrroloquinolin compounds of formula (1) or (II). In certain aspects, the pyrroloquinolin compounds are therapeutic, e.g., for treating a cell proliferative disorder. Also provided are conjugates that include the pyrroloquinolin compounds of the present disclosure. Compositions, e.g., pharmaceutical compositions, that include the pyrroloquinolin compounds and conjugates of the present disclosure are also provided. Further provided are therapeutic methods involving the administration of the pyrroloquinolin compounds, conjugates or compositions of the present disclosure. Kits that include the pyrroloquinolin compounds, conjugates or compositions are also provided. 

Pyrroloquinolin compounds and methods of using same

In particular, in alternative embodiments, the invention provides pharmaceutical compounds and formulations comprising a family of epoxyketone compounds, which include racemic mixtures or racemates, isomers, stereoisomers, diastereoisomers, derivatives and analogs, and methods for making and using them. In alternative embodiments, pharmaceutical compositions and formulations of the invention are administered to an individual in need thereof in an amount sufficient to treat, prevent, reverse and/or ameliorate an infection, disease or condition that can be ameliorated, treated, prevented or reversed by partially or completely inhibiting a chymotrypsin-like protease or a proteasome activity, including e.g., a retroviral infection such as human immunodeficiency virus-1 (HIV-1) infection, an immune disorder, a neurodegenerative disease or condition, or a cancer such as a myeloma or multiple myeloma, an adenocarcinoma such as a lung adenocarcinoma, a pancreatic cancer, a B-cell related cancer, and lymphomas such as non-Hodgkin's lymphoma.

Compositions and methods for inhibiting proteases

In alternative embodiments, the invention provides apratoxin F and apratoxin G compounds, which include apratoxin F and apratoxin G stereoisomers, derivatives and analogs compositions and methods. In alternative embodiments, the invention provides pharmaceutical compositions and formulations comprising apratoxin F (compound 6 of FIG.) and apratoxin G (compound 7 of FIG.) and their stereoisomers, derivatives and analogs. In alternative embodiments, pharmaceutical compositions and formulations of the invention are administered in an amount sufficient to treat, prevent and/or ameliorate a disease or condition that can be ameliorated by decreasing or inhibiting cell growth, e.g., pathological, uncontrolled or unwanted cell growth, e.g., a cancer or a metastases, or any disease or condition (e.g., allergy) or infection having a hyperproliferative cell growth component.

Compositions for ameliorating cell proliferative disorders and methods of making and using them

The present invention includes purified and isolated quassinoids and synthetically derived quassinoid analogs based on a picrasane carbon skeleton. Novel sidechains at C-15 incorporating water solubilizing agents such as glycine are discussed. Therapeutic methods taking advantage of anticancer, antiviral, and herbistatic properties of these quassinoids are disclosed, including use against solid tumors and human immunodeficiency virus infected cells.

Therapeutic quassinoid preparations with antineoplastic, antiviral, and herbistatic activity

A cryptophycin compound is provided having the structure: ##STR1## Further provided are methods of producing cryptophycins by total synthesis and methods of using cryptophycins in pharmaceuticals. It is a further object of this invention to use cryptophycins to inhibit the proliferation of mammalian cells. Moreover, methods of using cryptophycins to treat neoplasia is also provided.

Cryptophycins from synthesis

Therapeutic Quassinoid preparations with antineoplastic, antiviral, and

A cryptophycin compound is provided having the structure: ##STR1## Further provided are methods for producing novel cryptophycins from the Nostoc sp. of blue-green algae (cyanobacteria). Pharmaceutical compositions comprising novel cryptophycins are also provided, as are methods for using cryptophycins to inhibit the proliferation of hyperproliferative cells. Further provided are methods for using cryptophycins to inhibit the proliferation of hyperproliferative cells with drug resistant phenotypes, and to treat pathological conditions, such as neoplasia.

Cryptophycins

Therapeutic quassinoid preparations with antineoplastic antiviral, and

Quassinoid compounds, compositions, and methods of using them for treating cells and solid tumors, and inhibiting plant growth. The quassinoid derivatives herein are 11,20-epoxy-1,11,12-trihydroxypicras-3-ene-2,16 diones: ##STR1##

Therapeutic quassinoid preparations with antineoplastic, antiviral, and

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Shelby Township, MI, United States of America

Frederick A Valeriote