The present disclosure relates generally to therapeutic agents that may be useful as modulators of Integrated Stress Response (ISR) pathway.

The present disclosure relates generally to therapeutic agents that may be useful as modulators of Integrated Stress Response (ISR) pathway.

To provide a medicament for safely treating a patient in need of treatment with pemafibrate, a salt thereof, or a solvate of any of these (hereinafter also referred to as pemafibrate therapy). A medicament for treating a patient in need of pemafibrate therapy, the medicament comprising the step of avoiding or suspending concomitant use of pemafibrate, a salt thereof, or a solvate of any of these as an active ingredient in order to suppress an increase in plasma concentration of pemafibrate when the treatment is combined with a medicament containing an OATP1B inhibitor, or the step of reducing the dose of pemafibrate, a salt thereof, or a solvate of any of these.

To provide a medicament for safely treating a patient in need of treatment with pemafibrate, a salt thereof, or a solvate of any of these (hereinafter also referred to as pemafibrate therapy). A medicament for treating a patient in need of pemafibrate therapy, the medicament comprising the step of avoiding or suspending concomitant use of pemafibrate, a salt thereof, or a solvate of any of these as an active ingredient in order to suppress an increase in plasma concentration of pemafibrate when the treatment is combined with a medicament containing an OATP1B inhibitor, or the step of reducing the dose of pemafibrate, a salt thereof, or a solvate of any of these.

Provided is a bicyclic compound having an acetyl-CoA carboxylase inhibitory action. A compound represented by the formula:

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wherein each symbol is as described in the DESCRIPTION, or a salt thereof has an acetyl-CoA carboxylase inhibitory action, is useful for the prophylaxis or treatment of cancer, inflammatory diseases and the like, and has superior efficacy.

The present invention relates to a method for selecting an immunomodulatory kit, selected for an individual patient, for use in the treatment of patients suffering from myeloid leukemias. Different kits are available for selection and ex vivo testing which are composed of substances that have different immunomodulatory effects on leukemia cells. Each kit particularly contains GM-CSF and one (or two) more substances, selected from PICIBANIL, PGE.sub.1, PGE.sub.2, CALCIMYCIN and TNFα, as well as pharmaceutically acceptable adjuvants. The clinical aim is to modify, once the individually selected immunomodulatory kits were administered, blast cells in the body of the patient such that they turn into a “vaccine” which is able to activate the immunoreactive cells (of the patient or of the stem cell donor) in the body against blast cells.

The present invention relates to a method for selecting an immunomodulatory kit, selected for an individual patient, for use in the treatment of patients suffering from myeloid leukemias. Different kits are available for selection and ex vivo testing which are composed of substances that have different immunomodulatory effects on leukemia cells. Each kit particularly contains GM-CSF and one (or two) more substances, selected from PICIBANIL, PGE.sub.1, PGE.sub.2, CALCIMYCIN and TNFα, as well as pharmaceutically acceptable adjuvants. The clinical aim is to modify, once the individually selected immunomodulatory kits were administered, blast cells in the body of the patient such that they turn into a “vaccine” which is able to activate the immunoreactive cells (of the patient or of the stem cell donor) in the body against blast cells.

The present invention relates to a method for selecting an immunomodulatory kit, selected for an individual patient, for use in the treatment of patients suffering from myeloid leukemias. Different kits are available for selection and ex vivo testing which are composed of substances that have different immunomodulatory effects on leukemia cells. Each kit particularly contains GM-CSF and one (or two) more substances, selected from PICIBANIL, PGE.sub.1, PGE.sub.2, CALCIMYCIN and TNFα, as well as pharmaceutically acceptable adjuvants. The clinical aim is to modify, once the individually selected immunomodulatory kits were administered, blast cells in the body of the patient such that they turn into a “vaccine” which is able to activate the immunoreactive cells (of the patient or of the stem cell donor) in the body against blast cells.

It is provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and/or treatment of transthyretin-associated amyloidosis. It is also provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and/or treatment of transthyretin-associated amyloidosis in combination therapy with another COMT inhibitor, a benzoxazole derivative, iododiflunisal, diflunisal, resveratrol, tauroursodeoxycholic acid, doxocycline, or epigallocatechin-3-gallate.

It is provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and/or treatment of transthyretin-associated amyloidosis. It is also provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and/or treatment of transthyretin-associated amyloidosis in combination therapy with another COMT inhibitor, a benzoxazole derivative, iododiflunisal, diflunisal, resveratrol, tauroursodeoxycholic acid, doxocycline, or epigallocatechin-3-gallate.