The instant invention relates to combinations of the compound of formula (I) or pharmaceutically acceptable salts thereof with other active pharmaceutical ingredients (I), pharmaceutical compositions comprising them, and their use as medicaments, particularly for the treatment of hematological malignancies.

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Disclosed herein is the compound (R)-1-(4-(6-(2-(4-(3,3-difluorocyclobutoxy)-6-methylpyridin-2-yl)acetamido) pyridazin-3-yl)-2-fluorobutyl)-N-methyl-1H-1,2,3-triazole-4-carboxamide, and salt forms and polymorphs thereof demonstrating improved exposure after oral dosing. Methods of inhibition GLS1 activity in a human or animal subject are also provided.

Disclosed herein is the compound (R)-1-(4-(6-(2-(4-(3,3-difluorocyclobutoxy)-6-methylpyridin-2-yl)acetamido) pyridazin-3-yl)-2-fluorobutyl)-N-methyl-1H-1,2,3-triazole-4-carboxamide, and salt forms and polymorphs thereof demonstrating improved exposure after oral dosing. Methods of inhibition GLS1 activity in a human or animal subject are also provided.

Disclosed herein is the compound (R)-1-(4-(6-(2-(4-(3,3-difluorocyclobutoxy)-6-methylpyridin-2-yl)acetamido) pyridazin-3-yl)-2-fluorobutyl)-N-methyl-1H-1,2,3-triazole-4-carboxamide, and salt forms and polymorphs thereof demonstrating improved exposure after oral dosing. Methods of inhibition GLS1 activity in a human or animal subject are also provided.

Described herein is a method of sensitizing a cancer in a subject and methods of treating, slowing the progression of, reducing the severity of, preventing the recurrence of, and/or reducing the recurrence likelihood of a cancer in a subject. The invention further provides for a method of preventing the recurrence of and/or reducing the recurrence likelihood of a cancer in a subject who has been treated with a cancer therapy.

Described herein is a method of sensitizing a cancer in a subject and methods of treating, slowing the progression of, reducing the severity of, preventing the recurrence of, and/or reducing the recurrence likelihood of a cancer in a subject. The invention further provides for a method of preventing the recurrence of and/or reducing the recurrence likelihood of a cancer in a subject who has been treated with a cancer therapy.

The present invention related to a brain tumor-targeting peptide, a coding nucleic acid thereof, and a vector and host cell comprising the coding nucleic acid. The targeting peptide linked to a diagnostic marker can be used in brain tumor diagnosis, especially in brain tumor imaging; and the targeting peptide when linked to a therapeutic drug can carry the drug directly to a brain tumor lesion so as to achieve brain tumor treatment.

The present invention related to a brain tumor-targeting peptide, a coding nucleic acid thereof, and a vector and host cell comprising the coding nucleic acid. The targeting peptide linked to a diagnostic marker can be used in brain tumor diagnosis, especially in brain tumor imaging; and the targeting peptide when linked to a therapeutic drug can carry the drug directly to a brain tumor lesion so as to achieve brain tumor treatment.

The current disclosure relates to therapeutic treatments and diagnostic methods for esophageal cancer based on the expression level of biomarker miRNAs. Aspects of the disclosure relate to a method of treating esophageal cancer (EC) in a patient, said method comprising: diagnosing the patient with esophageal cancer when the patient is determined to have an elevated or decreased level of expression of one or more miRNAs selected from mir-15b, miR-17, mir-18a, mir-21, mir-23a, mir-24-2, mir-25, mir-27a, mir-93, mir-103, mir-106b, mir-129-2, mir-139, mir-146b, mir-148a, mir-151, miR-155, mir-181a-1, mir-181a, mir-181b-1, mir-181b, mir-182, mir-183, mir-192, mir-194-1, mir-194-2, mir-196a-1, mir-196a-2, mir-196b, mir-205, mir-215, mir-223, mir-224, mir-335, mir-338, mir-375, mir-421, mir-484, mir-505, mir-769, mir-944, mir-1468, mir-3648, and let-7i in a sample from a patient relative to the expression level of the one or more miRNAs in a control sample; and administering an effective amount of an esophageal treatment to the diagnosed patient.

The current disclosure relates to therapeutic treatments and diagnostic methods for esophageal cancer based on the expression level of biomarker miRNAs. Aspects of the disclosure relate to a method of treating esophageal cancer (EC) in a patient, said method comprising: diagnosing the patient with esophageal cancer when the patient is determined to have an elevated or decreased level of expression of one or more miRNAs selected from mir-15b, miR-17, mir-18a, mir-21, mir-23a, mir-24-2, mir-25, mir-27a, mir-93, mir-103, mir-106b, mir-129-2, mir-139, mir-146b, mir-148a, mir-151, miR-155, mir-181a-1, mir-181a, mir-181b-1, mir-181b, mir-182, mir-183, mir-192, mir-194-1, mir-194-2, mir-196a-1, mir-196a-2, mir-196b, mir-205, mir-215, mir-223, mir-224, mir-335, mir-338, mir-375, mir-421, mir-484, mir-505, mir-769, mir-944, mir-1468, mir-3648, and let-7i in a sample from a patient relative to the expression level of the one or more miRNAs in a control sample; and administering an effective amount of an esophageal treatment to the diagnosed patient.