Compounds, tautomers and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula Ia, ##STR00001##
as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

A condensed cyclic compound represented by Formula 1: ##STR00001## wherein in Formula 1, A.sub.1, A.sub.11, X.sub.21, XY.sub.1, XY.sub.11, R.sub.4, R.sub.14, b4, b14, c1, and c11 are as described in the specification.

The present disclosure in part provides compounds (i.e., PEG lipids) which are useful in pharmaceutical compositions, cosmetic compositions, and drug delivery systems, e.g, for use in lipid nanoparticle (LNP) formulations. The present disclosure also provides LNP formulations comprising PEG lipids described herein, and methods of using the same. For example, the LNPs provided herein are useful for the delivery of an agent (e.g, therapeutic agent) to a subject. The PEG lipids and LNPs provided herein, in certain embodiments, exhibit increased PEG shedding compared to existing PEG lipids and LNP formulations.

The present disclosure relates to uses of an ERK5 inhibitor, e.g., ERK5-in-1, for treating a glioma in a pediatric human subject. In certain embodiments, the glioma can be a pediatric high-grade glioma (PHGG), e.g., a diffuse intrinsic pontine glioma (DIPG), and/or a H3.3-mutated glioma (e.g., a H3K27M-mutated glioma). The present disclosure further provides pharmaceutical compositions and kits that include an ERK5 inhibitor.

The present disclosure relates to uses of TG02, for treating a glioma in a pediatric human subject. In certain embodiments, the glioma can be a pediatric high-grade glioma (PHGG), e.g., a diffuse intrinsic pontine glioma (DIPG), and/or a H3.3-mutated glioma (e.g., a H3K27M-mutated glioma). The present disclosure further provides pharmaceutical compositions and kits that include an ERK5 inhibitor.

The present disclosure relates to uses of TG02, for treating a glioma in a pediatric human subject. In certain embodiments, the glioma can be a pediatric high-grade glioma (PHGG), e.g., a diffuse intrinsic pontine glioma (DIPG), and/or a H3.3-mutated glioma (e.g., a H3K27M-mutated glioma). The present disclosure further provides pharmaceutical compositions and kits that include an ERK5 inhibitor.

The present invention provides prodrugs and methods of use thereof.

Methods of inhibiting MMP-9 are provided. The methods of inhibiting MMP-9 include methods of inhibiting IL-6/TNF-α crosstalk mediated expression and/or secretion of MMP-9. The inhibition of the IL-6/TNF-α crosstalk pathway may be accomplished using an IL-6 signaling inhibitor, such as AG490 or SC-144. The methods may also include the treatment of dieses through the inhibition of IL-6/TNF-α crosstalk mediated production of MMP-9. In an embodiment the methods may include preventing the progression of cancer or cardiovascular disease through the inhibition of the IL-6/TNF-α crosstalk pathway.

Methods of inhibiting MMP-9 are provided. The methods of inhibiting MMP-9 include methods of inhibiting IL-6/TNF-α crosstalk mediated expression and/or secretion of MMP-9. The inhibition of the IL-6/TNF-α crosstalk pathway may be accomplished using an IL-6 signaling inhibitor, such as AG490 or SC-144. The methods may also include the treatment of dieses through the inhibition of IL-6/TNF-α crosstalk mediated production of MMP-9. In an embodiment the methods may include preventing the progression of cancer or cardiovascular disease through the inhibition of the IL-6/TNF-α crosstalk pathway.

The present invention relates to compounds of the formula I or II: (I) (II) processes for their preparation and their use as pharmaceutical agents or compositions in the treatment, of neurological disorders. ##STR00001##