Provided are methods and compositions for treating cancers in patients carrying an IDH1 mutation using a combination of an inhibitor of a mutant IDH1 enzyme and an AML induction and consolidation therapy.

Disclosed are compounds to the treatment of infectious diseases and methods of treating such diseases. The compounds are derivatives of clevudine.

Disclosed are compounds to the treatment of infectious diseases and methods of treating such diseases. The compounds are derivatives of clevudine.

The present invention provides a compound having the structure: ##STR00001## wherein X is a therapeutic agent containing at least one amine nitrogen and the amine nitrogen on the therapeutic agent covalently bonds directly to carbon ; Z is CH.sub.3 or CF.sub.3; R.sub.1 is H, NR.sub.2R.sub.3, NHC(O)R.sub.4, NHC(O)OR.sub.4, CH.sub.2C(O)NR.sub.5R.sub.6, OR.sub.7, CO.sub.2R.sub.7, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, aryl, or heteroaryl, wherein R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6 and R.sub.7 are each, independently, H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, an amino acid or an oligopeptide; wherein an amine of the amino acid or oligopeptide is substituted or unsubstituted; and n is an integer from 0 to 6;
or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

The present invention provides a compound having the structure: ##STR00001## wherein X is a therapeutic agent containing at least one amine nitrogen and the amine nitrogen on the therapeutic agent covalently bonds directly to carbon ; Z is CH.sub.3 or CF.sub.3; R.sub.1 is H, NR.sub.2R.sub.3, NHC(O)R.sub.4, NHC(O)OR.sub.4, CH.sub.2C(O)NR.sub.5R.sub.6, OR.sub.7, CO.sub.2R.sub.7, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, aryl, or heteroaryl, wherein R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6 and R.sub.7 are each, independently, H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, an amino acid or an oligopeptide; wherein an amine of the amino acid or oligopeptide is substituted or unsubstituted; and n is an integer from 0 to 6;
or a diastereomer, enantiomer or pharmaceutically acceptable salt of the compound.

Methods and compositions are provided for oligonucleotides that bind targets of interest. The targets include cells and microvesicles, such as those derived from various diseases. The oligonucleotides can be used for diagnostic and therapeutic purposes. The target of the oligonucleotides can be a target such as PARP1, HIST1H1B, HIST1H1D, NCL, FBL, SFPQ, RPL12, ACTB, HIST1H4A, SSBP1, NONO, H2AFJ, and DDX21, or a complex, subunit or fragment thereof.

Methods and compositions are provided for oligonucleotides that bind targets of interest. The targets include cells and microvesicles, such as those derived from various diseases. The oligonucleotides can be used for diagnostic and therapeutic purposes. The target of the oligonucleotides can be a target such as PARP1, HIST1H1B, HIST1H1D, NCL, FBL, SFPQ, RPL12, ACTB, HIST1H4A, SSBP1, NONO, H2AFJ, and DDX21, or a complex, subunit or fragment thereof.

Disclosed is an oligonucleotide-modified nucleic acid containing at least one 1--D-arabinofuranosylcytosine as a modified nucleic acid having therapeutic efficacies and guanosine. More particularly, a novel oligonucleotide-modified nucleic acid containing at least one modified nucleic acid (N) having therapeutic efficacies and being rich in guanosine (G) is synthesized and the fact that the novel oligonucleotide-modified nucleic acid has excellent apoptotic activities on blood cancer cells and drug-resistant blood cancer cells is identified. Based on this, provided is a composition for preventing, ameliorating or treating blood cancer, containing the novel oligonucleotide-modified nucleic acid, and the novel oligonucleotide-modified nucleic acid or a pharmaceutically acceptable salt thereof as an active ingredient.

Among other things, the present disclosure provides designed oligonucleotides, compositions, and methods of use thereof. In some embodiments, the present disclosure provides technologies useful for reducing levels of transcripts. In some embodiments, the present disclosure provides technologies useful for modulating transcript splicing. In some embodiments, provided technologies can alter splicing of a dystrophin (DMD) transcript. In some embodiments, the present disclosure provides methods for treating diseases, such as Duchenne muscular dystrophy, Becker's muscular dystrophy, etc.

Among other things, the present disclosure provides designed oligonucleotides, compositions, and methods of use thereof. In some embodiments, the present disclosure provides technologies useful for reducing levels of transcripts. In some embodiments, the present disclosure provides technologies useful for modulating transcript splicing. In some embodiments, provided technologies can alter splicing of a dystrophin (DMD) transcript. In some embodiments, the present disclosure provides methods for treating diseases, such as Duchenne muscular dystrophy, Becker's muscular dystrophy, etc.