Abstract: The present invention relates to new compounds of formula (I): as modulators of serotonin receptor 1B (5-HTR1B) also known as 5-hydroxytryptamine receptor 1B (5-HT1B). The compounds are of potential utility in the treatment of diseases and conditions mediated by serotonin receptor type 1B (5-HTR1B), such as cancer, including blood cancer and solid tumors, respiratory diseases and hepatic disorders.

Abstract: The invention relates to a combination comprising an antineoplastic agent, e.g. an antimetabolite antineoplastic agent and a type 1 serotonin receptor (HTR 1)modulator, e.g. a HTR1 antagonist. In addition the invention relates to a pharmaceutical composition comprising a combination of the invention and a pharmaceutically acceptable excipient. The invention also relates to the combination and pharmaceutical composition according to the invention for use in medicine, particularly for use in the prevention and/or treatment of a hematological malignancy.

Abstract: The invention relates to a serotonin receptor (5-HTR) inhibitor selected from the group consisting of a type 1 5-HTR inhibitor and a type 2 5-HTR inhibitor for use in the prevention and/or treatment of a haematological malignancy. Additionally, the invention relates to in vitro methods for the identification or isolation of a malignant cell from a haematological malignancy or for diagnosing a haematological malignancy based on detecting the expression of type 1 5-HTR and/or type 2 5-HTR. Furthermore, the invention relates to in vitro methods for determining the prognosis, for monitoring the effect of a therapy or for designing a customized therapy in a subject suffering from a haematological malignancy based on determining the levels of type 1 5-HTR and or type 2 5-HTR.

Abstract: The invention relates to a combination comprising an antineoplastic agent, e.g. an antimetabolite antineoplastic agent and a type 1 serotonin receptor (HTR1) modulator, e.g. a HTR1 antagonist. In addition the invention relates to a pharmaceutical composition comprising a combination of the invention and a pharmaceutically acceptable excipient. The invention also relates to the combination and pharmaceutical composition according to the invention for use in medicine, particularly for use in the prevention and/or treatment of a hematological malignancy.

Abstract: The invention relates to a serotonin receptor (5-HTR) inhibitor selected from the group consisting of a type 1 5-HTR inhibitor and a type 2 5-HTR inhibitor for use in the prevention and/or treatment of a haematological malignancy. Additionally, the invention relates to in vitro methods for the identification or isolation of a malignant cell from a haematological malignancy or for diagnosing a haematological malignancy based on detecting the expression of type 1 5-HTR and/or type 2 5-HTR. Furthermore, the invention relates to in vitro methods for determining the prognosis, for monitoring the effect of a therapy or for designing a customized therapy in a subject suffering from a haematological malignancy based on determining the levels of type 1 5-HTR and or type 2 5-HTR.

Abstract: The invention relates to a serotonin receptor (5-HTR) inhibitor selected from the group consisting of a type 1 5-HTR inhibitor and a type 2 5-HTR inhibitor for use in the prevention and/or treatment of a haematological malignancy. Additionally, the invention relates to in vitro methods for the identification or isolation of a malignant cell from a haematological malignancy or for diagnosing a haematological malignancy based on detecting the expression of type 1 5-HTR and/or type 2 5-HTR. Furthermore, the invention relates to in vitro methods for determining the prognosis, for monitoring the effect of a therapy or for designing a customized therapy in a subject suffering from a haematological malignancy based on determining the levels of type 1 5-HTR and or type 2 5-HTR.

Abstract: The invention relates to a combination comprising an antineoplastic agent, e.g. an antimetabolite antineoplastic agent and a type 1 serotonin receptor (HTR1) modulator, e.g. a HTR1 antagonist. In addition the invention relates to a pharmaceutical composition comprising a combination of the invention and a pharmaceutically acceptable excipient. The invention also relates to the combination and pharmaceutical composition according to the invention for use in medicine, particularly for use in the prevention and/or treatment of a hematological malignancy.

Abstract: The invention relates to a serotonin receptor (5-HTR) inhibitor selected from the group consisting of a type 1 5-HTR inhibitor and a type 2 5-HTR inhibitor for use in the prevention and/or treatment of a haematological malignancy. Additionally, the invention relates to in vitro methods for the identification or isolation of a malignant cell from a haematological malignancy or for diagnosing a haematological malignancy based on detecting the expression of type 1 5-HTR and/or type 2 5-HTR. Furthermore, the invention relates to in vitro methods for determining the prognosis, for monitoring the effect of a therapy or for designing a customized therapy in a subject suffering from a haematological malignancy based on determining the levels of type 1 5-HTR and or type 2 5-HTR.

Abstract: The invention relates to a serotonin receptor (5-HTR) inhibitor selected from the group consisting of a type 1 5-HTR inhibitor and a type 2 5-HTR inhibitor for use in the prevention and/or treatment of a haematological malignancy. Additionally, the invention relates to in vitro methods for the identification or isolation of a malignant cell from a haematological malignancy or for diagnosing a haematological malignancy based on detecting the expression of type 1 5-HTR and/or type 2 5-HTR. Furthermore, the invention relates to in vitro methods for determining the prognosis, for monitoring the effect of a therapy or for designing a customized therapy in a subject suffering from a haematological malignancy based on determining the levels of type 1 5-HTR and/or type 2 5-HTR.

Abstract: The invention relates to a serotonin receptor (5-HTR) inhibitor selected from the group consisting of a type 1 5-HTR inhibitor and a type 2 5-HTR inhibitor for use in the prevention and/or treatment of a haematological malignancy. Additionally, the invention relates to in vitro methods for the identification or isolation of a malignant cell from a haematological malignancy or for diagnosing a haematological malignancy based on detecting the expression of type 1 5-HTR and/or type 2 5-HTR. Furthermore, the invention relates to in vitro methods for determining the prognosis, for monitoring the effect of a therapy or for designing a customized therapy in a subject suffering from a haematological malignancy based on determining the levels of type1 5-HTR and/or type 2 5-HTR.

Abstract: Described are methods of treating a cancer comprising administering to a subject in need thereof an effective amount of a dopamine receptor (DR) antagonist. The DR antagonist may be a phenothiazine derivative, such as thioridazine or chlorpromazine. Optionally, the cancer is acute myeloid leukemia. Also described are methods for identifying subjects with cancer, methods for providing a prognosis for a subjects with cancer and methods for identifying subjects likely to be responsive to therapy with DR receptor antagonists. Methods for identifying cancer stem cells and chemotherapeutic compounds that are DR receptor antagonists as also provided. Also described are methods for the identification and validation of agents that target cancer stem cells.

Abstract: The present disclosure provides a method of generating progenitor cells, such as hematopoietic or neural progenitor cells, from fibroblasts, such as dermal fibroblasts, comprising providing fibroblasts that express or are treated with a POU domain containing gene or protein and culturing the cells under conditions that allow production of progenitor cells, without traversing the pluripotent state. Also provided is a method of isolating a subpopulation of fibroblasts with reprogramming potential comprising providing fibroblasts that express an Oct-4-reporter and isolating cells that are positive for the reporter. Further provided is a method of generating reprogrammed fibroblast-derived induced pluripotent stem cells. Also provided are uses and assays of the cells produced by the methods of the disclosure.

Abstract: Described are methods of treating a cancer comprising administering to a subject in need thereof an effective amount of a dopamine receptor (DR) antagonist. The DR antagonist may be a phenothiazine derivative, such as thioridazine or chlorpromazine. Optionally, the cancer is acute myeloid leukemia. Also described are methods for identifying subjects with cancer, methods for providing a prognosis for a subjects with cancer and/or subjects likely to be responsive to therapy with DR receptor antagonists. Methods for identifying cancer stem cells and chemotherapeutic compounds that are DR receptor antagonists as also provided.

Abstract: Described are methods of treating a cancer comprising administering to a subject in need thereof an effective amount of a dopamine receptor (DR) antagonist. The DR antagonist may be a phenothiazine derivative, such as thioridazine or chlorpromazine. Optionally, the cancer is acute myeloid leukemia. Also described are methods for identifying subjects with cancer, methods for providing a prognosis for a subjects with cancer and methods for identifying subjects likely to be responsive to therapy with DR receptor antagonists. Methods for identifying cancer stem cells and chemotherapeutic compounds that are DR receptor antagonists as also provided. Also described are methods for the identification and validation of agents that target cancer stem cells.

Abstract: The present disclosure provides a method of generating progenitor cells, such as hematopoietic or neural progenitor cells, from fibroblasts, such as dermal fibroblasts, comprising providing fibroblasts that express or are treated with a POU domain containing gene or protein and culturing the cells under conditions that allow production of progenitor cells, without traversing the pluripotent state. Also provided is a method of isolating a subpopulation of fibroblasts with reprogramming potential comprising providing fibroblasts that express an Oct-4-reporter and isolating cells that are positive for the reporter. Further provided is a method of generating reprogrammed fibroblast-derived induced pluripotent stem cells. Also provided are uses and assays of the cells produced by the methods of the disclosure.