The invention provides novel LRP5-binding polypeptides, and more specifically novel LRP5-binding immunoglobulin single variable domain constructs which can inhibit Wnt signaling pathways. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as cancer.

The invention provides novel LRP5-binding polypeptides, and more specifically novel LRP5-binding immunoglobulin single variable domain constructs which can inhibit Wnt signaling pathways. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as cancer.

Some embodiments of the disclosure include inventive compounds (e.g., compounds of Formula (I)) and compositions (e.g., pharmaceutical compositions) which inhibit IRAK and/or FLT3 and which can be used for treating, for example, certain diseases. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as hematopoietic cancers, myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), etc.), Additional embodiments provide disease treatment using combinations of the inventive IRAK and/or FLT3 inhibiting compounds with other therapies, such as cancer therapies.

The invention provides novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.

The present invention provides, in part, compounds of Formula I:

##STR00001##

and pharmaceutically acceptable salts thereof and N-oxides thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds and the uses of such compounds for the treatment of D1-mediated (or D1-associated) disorders including cognitive and motivational impairments and negative symptoms associated with illnesses such as schizophrenia, depression, bipolar disorder, Parkinson's disease, Mild cognitive impairment (MCI), Alzheimer's disease, lupus, Huntington's disease, Parkinson's, dyskinesia, ADHD, post-traumatic stress disorder, autism spectrum disorder, treatment-resistant depression, major depressive disorder (MDD), drug dependence, Tourette's syndrome, tardive dyskinesias as well as impairments associated with age, chronic stress, sleep deprivation, combat, chronic fatigue; endocrine or metabolic diseases such as hyperglycemia, dislipidemia, diabetes, obesity, and sepsis; and cardiovascular disorder such as hypertension.

The present invention relates to a dosage form comprising an aqueous solution of a vinca alkaloid drug or its pharmaceutically acceptable salt in a flexible infusion container, and a light protective secondary packaging containing the flexible infusion container, wherein the dosage form is ready-to-infuse and wherein the aqueous solution is stable at room temperature.

The present invention relates to a dosage form comprising an aqueous solution of a vinca alkaloid drug or its pharmaceutically acceptable salt in a flexible infusion container, and a light protective secondary packaging containing the flexible infusion container, wherein the dosage form is ready-to-infuse and wherein the aqueous solution is stable at room temperature.

The present invention provides, in part, compounds of Formula I:

##STR00001##

and pharmaceutically acceptable salts thereof and N-oxides thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds (N-oxides thereof or or pharmaceutically acceptable salts of the compound or the N-oxides) and the uses of such compounds (N-oxides thereof or or pharmaceutically acceptable salts of the compound or the N-oxides) for the treatment of D1-mediated (or D1-associated) disorders including cognitive and motivational impairments and negative symptoms associated with illnesses such as schizophrenia, depression, bipolar disorder, Parkinson's disease, Mild cognitive impairment (MCI), Alzheimer's disease, lupus, Huntington's disease, Parkinson's, dyskinesia, ADHD, post-traumatic stress disorder, autism spectrum disorder, treatment-resistant depression, major depressive disorder (MDD), drug dependence, Tourette's syndrome, tardive dyskinesias as well as impairments associated with age, chronic stress, sleep deprivation, combat, chronic fatigue; endocrine or metabolic diseases such as hyperglycemia, dislipidemia, diabetes, obesity, and sepsis; and cardiovascular disorder such as hypertension. The present invention further provides a D1 agonist with reduced D1R desensitization, a D1 agonist with a reduced -arrestin recruitment activity relative to Dopamine, a D1 agonist interacting significantly with the Ser188 but not significantly with the Ser202 of a D1R when binding to the D1R, a D1 agonist interacting less strongly the Asp103 and interacting less strongly with the Ser198 of a D1R when binding to the D1R, and their uses.

The present invention provides, in part, compounds of Formula I: ##STR00001##
and pharmaceutically acceptable salts thereof and N-oxides thereof; processes and intermediates for preparation of; and compositions and uses thereof. The present invention further provides D1 agonists with reduced D1R desensitization, D1 agonists with a reduced -arrestin recruitment activity relative to Dopamine, D1 agonists interacting significantly with the Ser188 but not significantly with the Ser202 of a D1R when binding to the D1R, D1 agonists interacting less strongly with the Asp103 and interacting less strongly with the Ser198 of a D1R when binding to the D1R, and their uses.

The present invention provides, in part, compounds of Formula I: ##STR00001##
and pharmaceutically acceptable salts thereof and N-oxides thereof; processes and intermediates for preparation of; and compositions and uses thereof. The present invention further provides D1 agonists with reduced D1R desensitization, D1 agonists with a reduced -arrestin recruitment activity relative to Dopamine, D1 agonists interacting significantly with the Ser188 but not significantly with the Ser202 of a D1R when binding to the D1R, D1 agonists interacting less strongly with the Asp103 and interacting less strongly with the Ser198 of a D1R when binding to the D1R, and their uses.