The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyrido[3,4-d]pyrimidin-4-one derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer, melanoma, and the like.

The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma, lung cancer), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject. ##STR00001##

The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyrido[3,4-d]pyrimidin-4-one derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer, melanoma, and the like.

Compounds for inhibiting human epithelial 15-lipoxygenase-2 (h15-LOX-2) are provided. Compounds according to certain embodiments modulate ferroptosis and generation of hydroperoxy eicosatetraenoic acids (HpETEs). In some embodiments, compounds described herein modulate eicosanoid mediator biosynthesis from leukotrienes (LTs) to pro-resolving mediator class of lipoxins (LXs). Methods for treating or preventing a human epithelial 15-lipoxygenase-2(h15-LOX-2)-mediated disease are also provided. Compositions for practicing the subject methods are also described.

Compounds for inhibiting human epithelial 15-lipoxygenase-2 (h15-LOX-2) are provided. Compounds according to certain embodiments modulate ferroptosis and generation of hydroperoxy eicosatetraenoic acids (HpETEs). In some embodiments, compounds described herein modulate eicosanoid mediator biosynthesis from leukotrienes (LTs) to pro-resolving mediator class of lipoxins (LXs). Methods for treating or preventing a human epithelial 15-lipoxygenase-2(h15-LOX-2)-mediated disease are also provided. Compositions for practicing the subject methods are also described.

The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyrido[3,4-d]pyrimidin-4-one derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer, melanoma, and the like.

The present invention relates to compounds of formula (I), ##STR00001##
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are as described herein, and their prodrugs or pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.

The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyrido[3,4-d]pyrimidin-4-one derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer, melanoma, and the like.

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.

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.