University of California

Impact Biomedicines, Inc.

Catriona Jamieson

Qingfei Jiang

Daniel Jacob Goff

Jessica Pham

Raymond Diep

Jane Isquith

John Hood

Dennis A Carson

Wolfgang J Wrasidlo

Michael D Burkart

James J La Clair

Kelly A Frazer

Tadeusz F Molinski

Christian L Barrett

Leslie Crews Robertson

Desheng Lu

Curtis L Scribner

Anil Sadarangani

Angela Court

Kelsey A Trieger

Annelie Schairer

Warren C Chan

Tymara Berry

Ifat Geron

Kristen Smith

Kim-Hien Dao

Provided herein, inter alia, are splice modulator compounds. The compounds include optically pure, stereospecific analogs of FD-895. The methods provided herein allow, for example, for scalable preparation of said compounds, and further allow, for example, use of said compounds for inhibiting spliceosome activity.

Anticancer and antifungal splice modulators

In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for treating or ameliorating a cancer by inhibiting expression or activity of Mouse Double Minute 2 homolog (MDM2), an APOBEC3G (A3G) protein, message (mRNA) or gene, and/or an ADAR1p150 protein, message (mRNA) or gene, e.g., by increasing the presence of in a cell or adding to a cell a molecule inhibitory to MDM2, APOBEC3G and/or ADAR1p150 expression, such as an miRNA that binds to MDM2, APOBEC3G and/or ADAR1p150 transcripts, or any molecule that can inhibit or destabilize the transcripts, resulting in decreased MDM2, APOBEC3G and/or ADAR1p150 expression, to treat a cancer such as leukemia, e.g., by inhibiting the propagation of a cancer cell, a leukemia cell, a leukemia stem cell (LSC) or a pre-leukemia cell stem cell (pre-LSC).

Anticancer compositions and methods for making and using them

The present disclosure provides methods of mitigating thiamine deficiency.

Methods of treating myeloproliferative disorders

The disclosure provides methods for determining the self-renewal potential of a cancer stem cell (CSC), or for predicting the drugability (susceptibility to a drug) of a CSC, and/or for predicting the progression of a cancer that corresponds to the CSC. In alternative embodiments, the disclosure provides methods for determining whether a CSC in a niche is more pro-apoptotic or more anti-apoptotic in relation to a normal stem cell or a CSC from another niche. In alternative embodiments, the disclosure provides methods for determining the prognosis or malignant potential of a cancer. In alternative embodiments, the disclosure provides methods determining the anti-apoptotic versus a pro-apoptotic potential of a cancer stem cell (CSC).

Methods for sensitizing a quiescent cancer stem cell to a BCR-ABL inhibitor

In alternative embodiments, the invention provides compositions and methods for inhibiting or ablating cancer stem cells. In alternative embodiments, the invention provides compositions and methods for inhibiting the action of double-stranded RNA-specific adenosine deaminases, or ADAR, enzymes. In alternative embodiments, the invention provides compositions and methods for treating, ameliorating or preventing diseases and conditions responsive to the inhibition of cell differentiation and/or self-renewal of dysfunctional cells, cancer cells, leukemia cells, hematopoietic stem cells or cancer stem cells, e.g., leukemia or Chronic Myeloid Leukemia (CML). In alternative embodiments, the invention provides compositions and methods for inhibiting a Sonic Hedgehog (Shh) pathway, e.g., by using a Smoothened (SMO) protein inhibitor. In alternative embodiments, the invention provides compositions and methods for measuring or determining, or predicting, chronic myelogenous leukemia (CML) progression, Leukemic Stem Cell (LSC) generation and/or tyrosine kinase inhibitor resistance. In alternative embodiments, the invention provides compositions and methods for determining or measuring the effectiveness of a treatment, a drug, a therapy or a diet for eliminating, killing or reducing the amounts of a leukemic stem cell (LSC) or cells.

Compositions and methods for cancer and cancer stem cell detection and elimination

In alternative embodiments, the invention provides compositions and methods for determining the self-renewal potential of a cancer stem cell (CSC) through analysis of the cross-talk between cell self-renewal pathways leading to deregulation and enhanced self-renewal of the CSC, or for predicting the drugability (susceptibility to a drug) of a CSC, and/or for predicting the progression of a cancer that corresponds to the CSC, the method comprising detecting and quantifying in CSCs one or more B-cell lymphoma-2 (Bcl-2) family protein isoform(s) or transcripts (mRNAs, messages) encoding one or more Bcl-2 family protein(s) or protein isoform(s) thereof. In alternative embodiments, the invention provides compositions and methods to determine and measure the levels of Wnt, glycogen synthase kinase-3 beta (GSK-3 beta), glycogen synthase kinase-3 alpha (GSK-3 alpha), and/or Sonic Hedgehog Homolog (SHH or Shh) family proteins and alternatively spliced transcripts (mRNAs), and Wnt, GSK3beta, GSK3alpha and/or Shh family protein and alternatively spliced transcript ratios in cancer cells, e.g., stem cells, e.g., CSCs, for diagnostic, drug discovery and prognostic purposes.

Compositions and methods for determining cancer stem cell self-renewal potential

The invention provides dBHD-based compositions and dBHD analog compositions, and pharmaceutical compositions comprising them, e.g., in the form of liposomes and nanoparticles comprising them, and methods of making and using them. In one embodiment, these dBHD analogs are used to inhibit a dysfunctional stem cell and/or a cancer (tumor) stem cell.

Wnt signaling inhibitors, and methods for making and using them

Growing community of inventors

La Jolla, CA, United States of America

Catriona Jamieson