Abstract: The present disclosure relates to mdm2 inhibitors for use in specific dosing schedules. It was found that if sufficiently potent or, in alternative, sufficiently high dose of a Mdm2 inhibitor is used, it can cause antineoplastic effect by triggering much longer lasting antiproliferative mechanism in cells. The long lasting effect can sustain for several weeks after a single dose, which eliminates the need for daily treatment and allows administering the Mdm2i intermittently. A treatment with the intermittent dosing schedule of a Mdm2 inhibitor can be combined with a daily treatment of the Mdm2i or with another pharmaceutically acceptable ingredient.

Abstract: The present invention relates to HDM2-p53 interaction inhibitors for use in the treatment of cancer, wherein the drug is administered by a high dose intermittent dosing regimen. The present invention relates in particular to the HDM2-p53 interaction inhibitor HDM20I and the dosing regimen di, d8 of a 4 week cycle.

Abstract: The present invention relates to HDM2-p53 interaction inhibitors for use in the treatment of cancer, wherein the drug is administered by a high dose intermittent dosing regimen. The present invention relates in particular to the HDM2-p53 interaction inhibitor HDM20I and the dosing regimen di, d8 of a 4 week cycle.

Abstract: The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

Abstract: The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

Abstract: The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

Abstract: The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

Abstract: The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

Abstract: The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

Abstract: The invention provides methods of monitoring differential gene expression of biomarkers to determine patient sensitivity to Human Double Minute inhibitors (MDM2i), methods of determining the sensitivity of a cell to an MDM2i by measuring biomarkers and methods of screening for candidate MDM2i.

Abstract: The invention provides methods of monitoring differential gene expression of biomarkers to determine patient sensitivity to Human Double Minute inhibitors (MDM2i), methods of determining the sensitivity of a cell to an MDM2i by measuring biomarkers and methods of screening for candidate MDM2i.

Abstract: The invention provides methods of monitoring differential gene expression of biomarkers to determine patient sensitivity to Human Double Minute inhibitors (MDM2i), methods of determining the sensitivity of a cell to an MDM2i by measuring biomarkers and methods of screening for candidate MDM2i.

Abstract: The invention provides methods of monitoring differential gene expression of biomarkers to determine patient sensitivity to Human Double Minute inhibitors (MDM2i), methods of determining the sensitivity of a cell to an MDM2i by measuring biomarkers and methods of screening for candidate MDM2i.

Abstract: A therapeutic composition that includes an active portion of the lysyl oxidase pro-peptide in a pharmaceutically acceptable carrier substance and methods of using such a therapeutic composition are disclosed. The active agent does not have lysyl oxidase enzymatic activity. Preferably, the active polypeptide is active in inhibiting cell growth in soft agar and active in inhibiting tumor formation. In addition, the active polypeptide preferably comprises an active portion of the amino acid sequence given in SEQ ID NO.: 1 or SEQ ID NO.: 2, or conservative substitions thereof. Alternatively, the active polypeptide comprises a polypeptide comprising an active portion of an amino acid sequence selected from the group consisting of SEQ ID NOs.: 3-8, or conservative substitions thereof.