Supergen, Inc

Astex Pharmaceuticals, Inc.

Otsuka Pharmaceutical Company, Limited

Intas Pharmaceuticals Limited

Mayne Pharma LLC

Sanjeev Redkar

Pasit Phiasivongsa

Rajashree Joshi-Hangal

Ashok Y Gore

Hariprasad Vankayalapati

David J Bearss

Chunlin Tang

Harish Ravivarapu

Xichen Zhang

Stephanie Gong

William Alexander Denny

Xiao-Hui Liu

Swarna Gamage

Darby Brooke

Yong Xu

Joseph Rubinfeld

Krzysztof Swierczek

The invention provides derivatives of decitabine with superior chemical stability and shelf life, with similar physiological activity. The derivatives are provided in a non-aqueous formulation, which further stabilizes the derivatives. Methods of treating one or more myelodysplastic syndromes, leukemia, or solid tumours using the formulations are described.

Drug formulations

Oligonucleotide analogues are provided that incorporate 5-aza-cytosine in the oligonucleotide sequence, e.g., in the form of 5-aza-2'-deoxycytidine (decitabine) or 5-aza-cytidine. In particular, oligonucleotide analogues rich in decitabine-deoxyguanosine islets (DpG and GpD) are provided to target the CpG islets in the human genome, especially in the promoter regions of genes susceptible to aberrant hypermethylation. Such analogues can be used for modulation of DNA methylation, such as effective inhibition of methylation of cytosine at the C-5 position. Methods for synthesizing these oligonucleotide analogues and for modulating nucleic acid methylation are provided. Also provided are phosphoramidite building blocks for synthesizing the oligonucleotide analogues, methods for synthesizing, formulating and administering these compounds or compositions to treat conditions, such as cancer and hematological disorders.

Oligonucleotide analogues incorporating 5-aza-cytosine therein

The invention provides a method of preparing a lyophilized pharmaceutical composition containing a dinucleotide compound or a pharmaceutically-acceptable salt thereof. The process comprises dissolving the dinucleotide compound in a solvent comprising dimethylsulfoxide and optionally one or more co-solvents to form a solution, and then removing the solvent and any co-solvents by a freeze-drying process. Also provided by the invention are lyophilized pharmaceutical compositions and their use in medicine and in particular in the treatment of cancer.

Lyophilized pharmaceutical compositions

Oligonucleotide analogs are provided that incorporate 5-aza-cytosine in the oligonucleotide sequence, e.g., in the form of 5-aza-2'-deoxycytidine (decitabine) or 5-aza-cytidine. In particular, oligonucleotide analogs rich in decitabine-deoxyguanosine islets (DpG and GpD) are provided to target the CpG islets in the human genome, especially in the promoter regions of genes susceptible to aberrant hypermethylation. Such analogs can be used for modulation of DNA methylation, such as effective inhibition of methylation of cytosine at the C-5 position. Methods for synthesizing these oligonucleotide analogs and for modulating nucleic acid methylation are provided. Also provided are phosphoramidite building blocks for synthesizing the oligonucleotide analogs, methods for synthesizing, formulating and administering these compounds or compositions to treat conditions, such as cancer and hematological disorders.

The invention provides derivatives of decitabine with superior chemical stability and shelf life, with similar physiological activity. The derivatives are provided in a non-aqueous formulation, which further stabilizes the derivatives. Methods of treating one or more myelodysplastic syndromes, leukemia, or solid tumors using the formulations are described.

The present invention relates to pharmaceutical formulations comprising the protein kinase inhibitor, MP470, and methods of using same in treating conditions involving undesirable cell proliferation, such as cancer.

Pharmaceutical formulations comprising salts of a protein kinase inhibitor and methods of using same

Quinoline derivatives, particularly 4-(4-(4-(quinolin-4-ylamino)benzamido)phenylthio)pyrrolidine-2-carboxylic acid; 3-(4-(4-(quinolin-4-ylamino)benzamido)phenylthio)pyrrolidine; N-(4-(piperidin-4-ylthio)phenyl)-4-(quinolin-4-ylamino)-benzamide; and N-(4-(piperidin-3-ylthio)phenyl)-4-(quinolin-4-ylamino)-benzamide, or a physiologically acceptable salt thereof, are provided. Such quinoline derivatives can be used for modulation of DNA methylation, such as effective inhibition of methylation of cytosine at the C-5 position, for example via selective inhibition of DNA methyltransferase DNMT1. Methods for synthesizing numerous 4-anilinoquinoline derivatives and for modulating DNA methylation are provided. Also provided are methods for formulating and administering these compounds or compositions to treat conditions such as cancer and hematological disorders.

Quinoline derivatives for modulating DNA methylation

Quinoline derivatives, particularly 4-anilinoquinoline derivatives of formula (I), are provided: Such quinoline derivatives can be used for modulation of DNA methylation, such as effective inhibition of methylation of cytosine at the C-5 position, for example via selective inhibition of DNA methyltransferase DNMT 1. Methods for synthesizing numerous 4-anilinoquinoline derivatives and for modulating DNA methylation are provided. Also provided are methods for formulating and administering these compounds or compositions to treat conditions such as cancer and hematological disorders.

Growing community of inventors

Hayward, CA, United States of America

Sanjeev Redkar