An antitumor formulation comprising a biphenyl compound having LSD1 inhibitory activity or a salt thereof and one or more other antitumor agents that are administered in combination, the compound being represented by Formula (I): ##STR00001##
wherein ring A, ring B, R1 to R6, l, m, and n are as defined in the specification.

A patch preparation which can produce the effect for preventing any problems due to the misuse of the patch preparation, includes a support and a plaster wherein the plaster includes a) an aliphatic compound with hydrophilic group which is in solid state at room temperature, b) a non-aqueous adhesive, and c) a solvent with a vapor pressure of 1 kPa or more at 20° C.

A patch preparation which can produce the effect for preventing any problems due to the misuse of the patch preparation, includes a support and a plaster wherein the plaster includes a) an aliphatic compound with hydrophilic group which is in solid state at room temperature, b) a non-aqueous adhesive, and c) a solvent with a vapor pressure of 1 kPa or more at 20° C.

Disclosed herein are gastrointestinal tract (G1) bacteria and methods for treating or preventing an irradiation-induced intestinal damage in a subject, the methods comprising administering a G1 bacterium to the subject, wherein the G1 bacterium comprises a vector that comprises a polynucleotide encoding IL-22 and/or IFN-P, or a functional fragment thereof.

Disclosed herein are gastrointestinal tract (G1) bacteria and methods for treating or preventing an irradiation-induced intestinal damage in a subject, the methods comprising administering a G1 bacterium to the subject, wherein the G1 bacterium comprises a vector that comprises a polynucleotide encoding IL-22 and/or IFN-P, or a functional fragment thereof.

The present invention describes a pharmaceutical composition that includes a novel molecule with neuroprotective activity, to inhibit the neuroadaptations induced by opioids (tolerance and hyperalgesia) that lead to the successive escalation of its doses in the treatment of pain. In this way, it increases its analgesic efficacy in normal conditions and in neural damage, since this favors the appearance of tolerance/hyperalgesia and resistance to opioid treatment. Likewise, reduce the spontaneous signs of withdrawal associated with its withdrawal and consequently physical dependence and possible addiction. In addition, it describes a method for the treatment of pain with a neuropathic component that is supported by drug interaction and safety studies that show its synergy for the mechanical antihypernociceptive effect.

The present invention describes a pharmaceutical composition that includes a novel molecule with neuroprotective activity, to inhibit the neuroadaptations induced by opioids (tolerance and hyperalgesia) that lead to the successive escalation of its doses in the treatment of pain. In this way, it increases its analgesic efficacy in normal conditions and in neural damage, since this favors the appearance of tolerance/hyperalgesia and resistance to opioid treatment. Likewise, reduce the spontaneous signs of withdrawal associated with its withdrawal and consequently physical dependence and possible addiction. In addition, it describes a method for the treatment of pain with a neuropathic component that is supported by drug interaction and safety studies that show its synergy for the mechanical antihypernociceptive effect.

Provided herein are methods of using (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing hematological malignancies. The second active agent is one or more of an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, an EZH2 inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor, a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, a SUV420H1/H2 inhibitor, a CARM1 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a BIRC5 inhibitor, or a chemotherapy.

Provided herein are methods of using (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing hematological malignancies. The second active agent is one or more of an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, an EZH2 inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor, a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, a SUV420H1/H2 inhibitor, a CARM1 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a BIRC5 inhibitor, or a chemotherapy.

Neuropeptide FF receptor modulators based on a proline scaffold are provided which offer NPFF receptor potencies in the nanomolar range and antagonistic selectivity for the NPFF1 receptor. Methods, compounds and compositions for modulating the function of neuropeptide FF receptors are provided for pharmacotherapies capable of influencing conditions or disorders affected by the neuropeptide FF receptors.