The present disclosure is directed to methods of screening a compound for modulating activity at a TNF-like weak inducer of apoptosis (TWEAK) binding site on a cysteine-rich domain (CRD) of fibroblast growth factor-inducible 14 (Fn14). The present disclosure also provides heterocyclic compounds and pharmaceutically acceptable salts thereof and methods for the prevention, treatment, and amelioration of cell proliferative disorders with these compounds.

Provided are labeling reagents and methods of using the reagents for cell uptake measurements. The labeling reagents can be quinone-masked probes including fluorophores and/or luminophores.

The invention relates to the nucleotide and amino acid sequences, and to the activity and use, of the luciferases LuAL, Lu164, Lu16, Lu39, Lu45, Lu52 and Lu22.

The invention relates to prophylaxis and therapy of cancer. In particular there is provided a protein Tryptophan2,3-di-oxygenase (TDO) or peptide fragments here of that are capable of eliciting anti-cancer immune responses. Specifically, the invention relates to the use of TDO or peptides derived thereof or TDO specific T-cells for treatment of cancer. The invention thus relates to an anti-cancer vaccine which optionally may be used in combination with other immunotherapies and to TDO specific T-cells adoptively transferred or induced in vivo by vaccination as a treatment of cancer. It is an aspect of the invention that the medicaments herein provided may be used in combination with cancer chemotherapy treatment. A further aspect relates to the prophylaxis and therapy of infections by the same means as described above.

Described are coelenterazine analogues, methods for making the analogues, kits comprising the analogues, and methods of using the compounds for the detection of luminescence in luciferase-based assays.

Provided herein are isolated polynucleotide encoding modified click beetle luciferase polypeptides that have enhanced luminescence and longer wavelength near-infrared signals. The disclosure also relates to near-infrared bioluminescence systems that include said modified click beetle luciferase polypeptides and novel luciferin derivatives, as well as methods of using said modified click beetle luciferase polypeptides and bioluminescence systems.

The present application provides novel inhibitors of indoleamine 2,3-dioxygenase-1 and/or indoleamine 2,3-dioxygenase-2 and/or tryptophan 2,3-dioxygenase, metabolites thereof, and pharmaceutically acceptable salts or prodrugs thereof. Also provided are methods for preparing these compounds. A therapeutically effective amount of one or more of the compounds of formula (I) is useful in treating diseases resulting from dysregulation of the kynurenine pathway. Compounds of formula (I) act by inhibiting the enzymatic activity or expression of indoleamine 2,3-dioxygenase-1 and/or indoleamine 2,3-dioxygenase-2 and/or tryptophan 2,3-dioxygenase.

The present invention includes a method of inhibiting or reducing mTOR signaling or inhibition of indoleamine dioxygenase-1 (IDO1) in a subject with a proliferative disease, which comprises administering to the subject having or suspected to have the proliferative disease, a therapeutically or prophylactically effective amount of the compound of Formula I:

##STR00001##

or a pharmaceutically acceptable salt or solvate thereof.

Disclosed herein are methods, compositions, apparatus, systems and kits for performing polynucleotide amplification utilizing a pure polynucleotide polymerase. In some cases, disclosed herein are methods, compositions, apparatus, systems and kits for sequencing polynucleotides.

The disclosure provides antibodies that specifically bind human IDO and methods of use thereof. In some aspects, the disclosure is directed to methods of detecting IDO in a biological sample comprising contacting the biological sample with an antibody described herein.