Abstract: The invention provides TRF1 inhibitors and compositions comprising them for the treatment of a brain cancer, such as a glioblastoma, and particularly a glioblastoma multiforme (GBM). PI3K inhibitors can be among the TRF1 inhibitors used. The compositions can comprise more than one TRF1 inhibitor, being particularly advantageous that at least one of the inhibitors is a PI3K inhibitor and that at least a second possible TRF1 inhibitor present is selected from the group an RTK inhibitor, a MEK inhibitor, an ERK inhibitor, an HSP90 inhibitor, docetaxel and gemcitabine, because such compositions show a synergic effect. The invention also relates to a method for identifying compounds candidates to be used for treating glioblastoma or other cancers, which method is based on the identification of the compound as a TRF1 inhibitor.

Abstract: There is provided compounds of formula I, wherein R1, R2, R3 R4, R5, R6, R7a and R7b have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. CDK8 and/or Haspin kinase) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.

Abstract: There is provided compounds of formula I, wherein R1, R2, R3 R4, R5, R6, R7a and R7b have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. CDK8 and/or Haspin kinase) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.

Abstract: There is provided compounds of formula I, wherein R1, R2a, R2b, R2c, X, Y, Z, R3 and ring A/B have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K, PIM family kinase and/or mTOR) is desired and/or required, and particularly in the treatment of cancer. The invention also relates to combinations containing such compounds.

Abstract: There is provided compounds of formula (I), wherein R1, R2, R3 and R4 have meanings given in the description (and which compounds are optionally substituted as indicated in the description), and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PIM family kinase, such as PIM-1, PIM-2 and/or PIM-3) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease. There is also provided combinations comprising the compounds of formula (I).

Abstract: There is provided compounds of formula I, wherein R1, R2a, R2b, R2c, X, Y, Z, R3 and ring A/B have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K, PIM family kinase and/or mTOR) is desired and/or required, and particularly in the treatment of cancer. The invention also relates to combinations containing such compounds.

Abstract: Provided are chemical entities selected from compounds of formula (I), wherein R1, R2 and m have meanings given in the description, and pharmaceutically acceptable salts, solvates and stereoisomers thereof, which are inhibitors of ATR and are potentially useful in the treatment of cancer. Further provided are pharmaceutical compositions of the chemical entities, combination products containing the chemical entities, the use of the compositions as therapeutic agents, and methods of treatment using these compositions.

Abstract: There is provided compounds of formula I, wherein R1, R2a, R2b, R2c, X, Y, Z, R3 and ring A/B have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K, PIM family kinase and/or mTOR) is desired and/or required, and particularly in the treatment of cancer. The invention also relates to combinations containing such compounds.

Abstract: Provided are chemical entities selected from compounds of formula (I), wherein R1, R2 and m have meanings given in the description, and pharmaceutically acceptable salts, solvates and stereoisomers thereof, which are inhibitors of ATR and are potentially useful in the treatment of cancer. Further provided are pharmaceutical compositions of the chemical entities, combination products containing the chemical entities, the use of the compositions as therapeutic agents, and methods of treatment using these compositions.

Abstract: There is provided compounds of formula I, wherein R1, R2a, R2b, R2c, X, Y, Z, R3 and ring A/B have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K, PIM family kinase and/or mTOR) is desired and/or required, and particularly in the treatment of cancer. The invention also relates to combinations containing such compounds.

Abstract: There is provided compounds of formula (I), wherein R1, R2, R3 and R4 have meanings given in the description (and which compounds are optionally substituted as indicated in the description), and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PIM family kinase, such as PIM-1, PIM-2 and/or PIM-3) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease. There is also provided combinations comprising the compounds of formula (I).

Abstract: There is provided compounds of formula (I), wherein R1, R2, R3 and R4 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PIM family kinase, such as PIM-1, PIM-2 and/or PIM-3, and/or Flt3) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.

Abstract: The present invention relates to metalocarboxypeptidase inhibitors and to their natural protein variants or protein variants redesigned by engineering, as well as to peptidomimetic molecules derived from the above and used as antitumor agents.