The present invention is directed to compounds having the Formulae (Ia), (Ib), (Ic), or (Id); or the Formulae (II), (IIa), (IIb), or (IIc); or the Formulae (III), (IIIa), (IIIb), (IIIc), (IIId), or (IIIe), and pharmaceutically acceptable salts, solvates, clathrates and prodrugs of any Formula thereof, compositions thereof, and methods for the treatment of a condition associated with a dysfunction in proteostasis.

A bioorthogonal molecule can include a molecule having a structure according the above wherein R.sup.1-R.sup.8 are independently selected from H, a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group, COOH, COOR.sup.9, COR.sup.9, CONR.sup.9R.sup.10, CN, CF.sub.3, and SO.sub.2R.sup.9, and where R.sup.9 and R.sup.10 are independently selected from H and a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group, with the proviso that one of R.sup.3-R.sup.8 comprises a leaving group, and wherein X is O, S, N, SO, SO.sub.2, SR.sup.+, Se, PO.sub.2.sup.−, or NRR′.sup.+, and where R and R′ are independently selected from H or a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group. ##STR00001##

A bioorthogonal molecule can include a molecule having a structure according the above wherein R.sup.1-R.sup.8 are independently selected from H, a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group, COOH, COOR.sup.9, COR.sup.9, CONR.sup.9R.sup.10, CN, CF.sub.3, and SO.sub.2R.sup.9, and where R.sup.9 and R.sup.10 are independently selected from H and a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group, with the proviso that one of R.sup.3-R.sup.8 comprises a leaving group, and wherein X is O, S, N, SO, SO.sub.2, SR.sup.+, Se, PO.sub.2.sup.−, or NRR′.sup.+, and where R and R′ are independently selected from H or a substituted or unsubstituted C.sub.1-C.sub.4 alkyl or alkylene group. ##STR00001##

The present disclosure provides a compound represented by structural formula (I-0):

##STR00001##

or a pharmaceutically acceptable salt thereof useful for treating a cancer.

The present disclosure provides a compound represented by structural formula (I-0):

##STR00001##

or a pharmaceutically acceptable salt thereof useful for treating a cancer.

The present invention relates to compounds that inhibit Son of sevenless homolog 1 (SOS1) activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of treating cancer using the compounds and pharmaceutical compositions of the present invention.

The present invention relates to compounds that inhibit Son of sevenless homolog 1 (SOS1) activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of treating cancer using the compounds and pharmaceutical compositions of the present invention.

The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.

The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.

Compounds of Formula (I), methods of using said compounds singly or in combination with additional agents and compositions of said compounds for the treatment of cancer are disclosed.