According to the invention there is provided a compound of formula A1 which may be useful in the treatment of a condition or disorder ameliorated by the inhibition of the A.sub.1-A.sub.2b or, particularly, the A.sub.2a receptor wherein the compound of formula A1 has the structure, wherein, A represents Cy.sup.1 or Het.sup.A; Cy.sup.1 represents a 5- to 14-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one, two or three rings, which Cy.sup.1 group is optionally substituted by one or more R.sup.4a substituents; Het.sup.A represents a 5- to 14-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more hetermatoms selected from O, S and N, which heterocyclic group may comprise one, two or three rings and which HetA group is optionally substituted by one or more R4b substituents; B represents a Cy.sup.2 or Het.sup.B; Cy.sup.2 represents a 3- to 10-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one or two rings, which Cy.sup.2 group is optionally substituted by one or more R.sup.4c substituents; Het.sup.B represents a 3- to 10-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more heteroatoms selected from O, S and N, which heterocyclic group may comprise one or two rings and which Het.sup.B group is optionally substituted by one or more R.sup.4d substituents.

##STR00001##

According to the invention there is provided a compound of formula A1 which may be useful in the treatment of a condition or disorder ameliorated by the inhibition of the A.sub.1-A.sub.2b or, particularly, the A.sub.2a receptor wherein the compound of formula A1 has the structure, wherein, A represents Cy.sup.1 or Het.sup.A; Cy.sup.1 represents a 5- to 14-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one, two or three rings, which Cy.sup.1 group is optionally substituted by one or more R.sup.4a substituents; Het.sup.A represents a 5- to 14-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more hetermatoms selected from O, S and N, which heterocyclic group may comprise one, two or three rings and which HetA group is optionally substituted by one or more R4b substituents; B represents a Cy.sup.2 or Het.sup.B; Cy.sup.2 represents a 3- to 10-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one or two rings, which Cy.sup.2 group is optionally substituted by one or more R.sup.4c substituents; Het.sup.B represents a 3- to 10-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more heteroatoms selected from O, S and N, which heterocyclic group may comprise one or two rings and which Het.sup.B group is optionally substituted by one or more R.sup.4d substituents.

##STR00001##

This invention relates to combination therapies comprising an EZH2 inhibitor and a chemotherapeutic agent, and associated pharmaceutical compositions, methods of treatment, and pharmaceutical uses.

This invention relates to combination therapies comprising an EZH2 inhibitor and a chemotherapeutic agent, and associated pharmaceutical compositions, methods of treatment, and pharmaceutical uses.

Among the various aspects of the present disclosure is the provision of OXTR chaperones and methods of use thereof. An aspect of the present disclosure provides for a method of increasing the display of oxytocin receptor (OXTR) on a plasma membrane in a cell of a subject comprising: administering an OXTR chaperone, wherein the OXTR chaperone increases OXTR on a cell surface. Another aspect of the present disclosure provides for a method of increasing or restoring oxytocin sensitivity in a subject comprising: administering an OXTR chaperone, wherein the OXTR chaperone increases OXTR on a cell surface. Yet another aspect of the present disclosure provides for a method of increasing the efficacy of oxytocin or synthetic oxytocin in a subject comprising: administering an OXTR chaperone, wherein the OXTR chaperone increases OXTR on a cell surface.

Among the various aspects of the present disclosure is the provision of OXTR chaperones and methods of use thereof. An aspect of the present disclosure provides for a method of increasing the display of oxytocin receptor (OXTR) on a plasma membrane in a cell of a subject comprising: administering an OXTR chaperone, wherein the OXTR chaperone increases OXTR on a cell surface. Another aspect of the present disclosure provides for a method of increasing or restoring oxytocin sensitivity in a subject comprising: administering an OXTR chaperone, wherein the OXTR chaperone increases OXTR on a cell surface. Yet another aspect of the present disclosure provides for a method of increasing the efficacy of oxytocin or synthetic oxytocin in a subject comprising: administering an OXTR chaperone, wherein the OXTR chaperone increases OXTR on a cell surface.

The present invention relates to methods and pharmaceutical compositions for the treatment of lung cancer. The inventors showed that FHIT (also known as bis(5-adenosyl)-triphosphatase) regulates HER2 activity in lung tumor cells and that HER2 inhibitors reduce invasion induced by FHIT inhibition. In particular, the present invention relates to a method of treating lung cancer in a patient in need thereof comprising the steps of i) determining the expression level of FHIT in a tumor tissue sample obtained from the patient, ii) comparing the expression level determined at step i) with a predetermined reference value and iii) administering to the patient a therapeutically effective amount of at least one HER2 inhibitor when the expression level determined at step i) is lower than the predetermined reference level.

The present invention relates to methods and pharmaceutical compositions for the treatment of lung cancer. The inventors showed that FHIT (also known as bis(5-adenosyl)-triphosphatase) regulates HER2 activity in lung tumor cells and that HER2 inhibitors reduce invasion induced by FHIT inhibition. In particular, the present invention relates to a method of treating lung cancer in a patient in need thereof comprising the steps of i) determining the expression level of FHIT in a tumor tissue sample obtained from the patient, ii) comparing the expression level determined at step i) with a predetermined reference value and iii) administering to the patient a therapeutically effective amount of at least one HER2 inhibitor when the expression level determined at step i) is lower than the predetermined reference level.

The present disclosure provides pharmaceutical combinations comprising at least one spliceosome modulator and at least one inhibitor chosen from BCL2, BCL2/BCLxL, and BCLxL inhibitors. Also provided are methods of treating cancer comprising administering a therapeutically effective amount of at least one spliceosome modulator and a therapeutically effective amount of at least one inhibitor chosen from BCL2, BCL2/BCLxL, and BCLxL inhibitors.

The present disclosure provides pharmaceutical combinations comprising at least one spliceosome modulator and at least one inhibitor chosen from BCL2, BCL2/BCLxL, and BCLxL inhibitors. Also provided are methods of treating cancer comprising administering a therapeutically effective amount of at least one spliceosome modulator and a therapeutically effective amount of at least one inhibitor chosen from BCL2, BCL2/BCLxL, and BCLxL inhibitors.