Abstract: Provided is a clutch engaging arrangement for a clutch of a transmission arrangement. The clutch engaging arrangement includes a spring-loaded connecting rod having a connecting portion arranged at a distance from an engaging member of the clutch engaging arrangement when the engaging member assumes the first disengaged position.

Abstract: Use of lenvatinib, or a pharmaceutically acceptable salt thereof in combination with a compound of the formula MIV-818: or pharmaceutically acceptable salt thereof, in the treatment of liver cancer or liver metastases. The respective dosage regimes of the compounds can be delivered concurrently or alternately.

Abstract: The invention provides compounds of the formula: R1 is OR11, or NR5R5?; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(?O)R6, O(C?O)R6 or O(C?O)OR6; R5? is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.

Abstract: The invention provides compounds of the formula: R1 is OR11, or NR5R5?; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(?O)R6, O(C?O)R6 or O(C?O)OR6; R5? is H or C1-C6alkyl; R6 is C1-C6or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.

Abstract: The invention provides compounds of the formula: R1 is OR11, or NR5R5?; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(?O)R6, O(C?O)R6 or O(C?O)OR6; R5? is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.

Abstract: Combination therapy with sorafenib or regorafenib and a phosphoramidate prodrug of troxacitabine with the formula: where Y is C1-C8 straight or branched chain alkyl, X is H, halo, C3-C4cycloalkyl or C1-C4alkyl and Z is H or fluoro, or a pharmaceutically acceptable salt thereof, shows surprising utility in the treatment of liver cancer or liver metastasis.

Abstract: The invention provides compounds of the formula: R1 is OR11, or NR5R5?; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(?O)R6, O(C?O)R6 or O(C?O)OR6; R5? is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.

Abstract: The invention provides a compound of formula (I) wherein B is a nucleobase; U is O or S; Rx is —OC(?O)Ry, —OC(?O)CH(Ry)NH2, —OCH2OC(?O)Ry; Ry is optionally substituted alkyl or alkenyl or the side chain of a natural or unnatural amino acid R1 is H, or optionally substituted phenyl, benzyl, naphthyl, pyridyl or indolyl, or Rx and R1 together define a bond thus forming a cyclic phosphate; R2 and R2? together define the side chain of a natural or unnatural amino acid; R3 is optionally substituted alkyl, cycloalkyl, phenyl or benzyl; and pharmaceutically acceptable salts and compositions thereof which are useful in the treatment of cancer, especially leukemias.

Abstract: The invention provides compounds of the formula: R1 is OR11, or NR5R5?; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(?O)R6, O(C?O)R6 or O(C?O)OR6; R5? is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.

Abstract: The invention provides compounds of the formula: R1 is OR11, or NR5R5?; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(?O)R6, O(C?O)R6 or O(C?O)OR6; R5? is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.

Abstract: The invention provides compounds of the formula: R1 is OR11, or NR5R5?; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(?O)R6, O(C?O)R6 or O(C?O)OR6; R5? is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.

Abstract: The present invention relates to novel applications for inhibitors, notably small molecule inhibitors, of the protease in which the inhibitors are used in an immunooncology setting to treat certain cancers. This in turn means that the compounds are directed to immune components and not to the tumour tissue directly.

Abstract: Combination therapy with sorafenib or regorafenib and a phosphoramidate prodrug of troxacitabine with the formula: where Y is C1-C8 straight or branched chain alkyl, X is H, halo, C3-C4cycloalkyl or C1-C4alkyl and Z is H or fluoro, or a pharmaceutically acceptable salt thereof, shows surprising utility in the treatment of liver cancer or liver metastasis.

Abstract: The invention provides compounds of the formula: R1 is OR11, or NR5R5?; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(?O)R6, O(C?O)R6 or O(C?O)OR6; R5? is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.

Abstract: Combination therapy with sorafenib or regorafenib and a phosphoramidate prodrug of troxacitabine with the formula: where Y is C1-C8 straight or branched chain alkyl, X is H, halo, C3-C4cycloalkyl or C1-C4alkyl and Z is H or fluoro, or a pharmaceutically acceptable salt thereof, shows surprising utility in the treatment of liver cancer or liver metastasis.

Abstract: The invention provides compounds of the formula: R1 is OR11, or NR5R5?; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(?O)R6, O(C?O)R6 or O(C?O)OR6; R5 is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.

Abstract: The invention provides compounds of the formula: R1 is OR11, or NR5R5?; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(?O)R6, O(C?O)R6 or O(OQ)OR6; R5? is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.

Abstract: Combination therapy with sorafenib or regorafenib and a phosphoramidate prodrug of troxacitabine with the formula: where Y is C1-C8 straight or branched chain alkyl, X is H, halo, C3-C4cycloalkyl or C1-C4alkyl and Z is H or fluoro, or a pharmaceutically acceptable salt thereof, shows surprising utility in the treatment of liver cancer or liver metastasis.

Abstract: The invention provides compounds of the formula: R1 is OR11, or NR5R5?; R2 is H or F; R5 is H, OH, C1-C6 alkyl, OH, C(?O)R6, O(C?O)R6 or O(C?O)OR6; R5? is H or C1-C6 alkyl; R6 is C1-C6 alkyl or C3-C7 cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.

Abstract: A genetically modified Saccharomyces cerevisiae including an active fermentation pathway producing 3-HP expresses an exogenous gene expressing the aminotransferase YhxA from Bacillus cereus AH1272 catalyzing a transamination reaction between beta-alanine and pyruvate to produce malonate semialdehyde. The yeast may also express a 3-hydroxyisobutyrate dehydrogenase (HIBADH) and a 3-hydroxypropanoate dehydrogenase (3-HPDH) and aspartate 1-decarboxylase. Additionally the yeast may express pyruvate carboxylase and aspartate aminotransferase.