Abstract: This disclosure is in the field of medicinal chemistry, and relates to a new class of small-molecules having the Formula I, or a pharmaceutically acceptable salt or solvate thereof, or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, or an isotopic variant thereof, wherein the variables Ring A, X, R1a, R1b, R2, R3, R4, m, n, and p are described herein, which function as dual inhibitors of EGFR proteins and PI3K proteins. The disclosure further relates to the use of the compounds described herein as therapeutics for the treatment of diseases and conditions mediated by EGFR proteins and/or PI3K proteins, such as cancer and other diseases.

Abstract: This disclosure is in the field of medicinal chemistry, and relates to a new class of small-molecules having the Formula I, or a pharmaceutically acceptable salt or solvate thereof, or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, or an isotopic variant thereof, wherein the variables Ring A, X, R1a, R1b, R2, R3, R4, m, n, and p are described herein, which function as dual inhibitors of EGFR proteins and PI3K proteins. The disclosure further relates to the use of the compounds described herein as therapeutics for the treatment of diseases and conditions mediated by EGFR proteins and/or PI3K proteins, such as cancer and other diseases.

Abstract: The present invention relates to the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinazoline structure or a quinoline structure according to Formula I, wherein L, R1, R2, X1, X2, and X3 are described herein, which function as dual inhibitors of EGFR proteins and PI3K proteins. The invention further relates to their use as therapeutics for the treatment of EGFR and/or PI3K mediated diseases or conditions.

Abstract: This disclosure is in the field of medicinal chemistry, and relates to a new class of small-molecules having the Formula I, or a pharmaceutically acceptable salt or solvate thereof, or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, or an isotopic variant thereof, wherein the variables Ring A, X, R1a, R1b, R2, R3, R4, m, n, and p are described herein, which function as dual inhibitors of EGFR proteins and PI3K proteins. The disclosure further relates to the use of the compounds described herein as therapeutics for the treatment of diseases and conditions mediated by EGFR proteins and/or PI3K proteins, such as cancer and other diseases.

Abstract: A combination comprising a compound of Formula (I) and/or Formula (Ia), or a pharmaceutically acceptable salt thereof, and at least one immune checkpoint modulator. Methods for the prevention and treatment of a cancer comprises administering to a subject in need thereof, a therapeutically effective amount of a combination, the combination comprising: a compound of Formula (I) and/or Formula (Ia), or a pharmaceutically acceptable salt thereof, and at least one immune checkpoint modulator.

Abstract: This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a pyrido-pyrimidin-amine structure, a thieno-pyrimidin-amine structure, a thiazolo-pyrimidin-amine structure, a furo-pyrimidin-amine structure, an oxazolo-pyrimidin-amine structure, a purin-amine structure, a pyrrolo-pyrimidin-amine structure, an amino-naphthyridine-carbonitrile structure, an amino-thieno-pyridine-carbonitrile structure, an amino-thiazo-pyridine-carbonitrile structure, an amino-furo-pyridine-carbonitrile structure, an amino-oxazolo-pyridine-carbonitrile structure, an amino-imidazo-pyridine-carbonitrile structure, or an amino-pyrrolo-pyridine-carbonitrile structure which function as dual inhibitors of EGFR proteins and PI3K proteins, and their use as therapeutics for the treatment of cancer and other diseases.

Abstract: Modified MEK1 peptides and modified MEK2 peptides, polynucleotides encoding those peptides, and methods for purifying the peptides and crystallizing them as peptide: cofactor: ligand complexes have been discovered. The three-dimensional structures of MEK1 peptide and MEK2 peptide, including the cofactor- and ligand-binding pockets, and uses of this information, for example, in molecular replacement and the modification, design and screening of compounds that may associate with MEK1, MEK2, or peptides structurally related thereto, have also been discovered.