HCMV US11 based therapeutics that can be used to target and reduce the activity of the FcRn protein are provided. Methods of treating auto-immune mediated and albumin-mediated diseases in a subject are provided that comprise administration of HCMV US11 protein, polypeptide fragments, or variants thereof, as well as methods for preventing, or treating, infections of HCMV through administration of a US11 inhibitor. US11 protein containing vaccine compositions are also provided for stimulation of an anti-US11 immune response for protection against HCMV infection.

The present invention is related to a method for detecting and identifying protein-protein or protein-small molecule interactions using a bait and prey system. It is also related to bait and prey proteins, small molecules and constructs that are used for the methods described herein.

Provided herein are methods for identifying pairs of protein binding partners, mutations of which may inform the discovery of pharmaceutically useful small molecules. The methods disclosed herein may allow for the adaptation of the native protein degradation system to modulate specific disease targets at the protein level, in particular, for targets that have long been considered undruggable.

The invention pertains to a heterobifunctional molecule comprising a first and a second binding domain, wherein i) the first binding domain is capable of specific binding to a transmembrane E3 ubiquitin ligase; and ii) the second binding domain is capable of specific binding to a transmembrane protein, wherein simultaneous binding of the heterobifunctional molecule to the transmembrane E3 ubiquitin ligase and the transmembrane protein results in ubiquitination and internalisation of the transmembrane protein. The invention further pertains to the heterobifunctional molecule for use in the treatment of a disease, wherein preferably the disease is at least one of cancer, an auto-immune disease, an inflammatory disease, an infectious disease and a hereditary disease.

The present invention relates to the use of an inhibitor of Rad18 expression or activity, in treating a tumor or in sensitizing a patient affected with a tumor, to a treatment with an antineoplastic agent that is a DNA damaging chemotherapeutic agent so to both reduce the self renewal of cancer stem cells and increase the DNA damage response thus boosting apoptotic cell death.

The invention relates to compounds and compositions capable of silencing, in a specific manner, the mRNA of isoform beta of the PIAS2 protein, as well as to the use thereof for the treatment of cancer, and particularly anaplastic carcinoma of the thyroid.

Provided herein are methods for identifying pairs of protein binding partners, mutations of which may inform the discovery of pharmaceutically useful small molecules. The methods disclosed herein may allow for the adaptation of the native protein degradation system to modulate specific disease targets at the protein level, in particular, for targets that have long been considered undruggable.

The invention pertains to a method to identify an effective combination of a transmembrane E3 ubiquitin ligase and a membrane-bound protein, wherein the combination is effective when the transmembrane E3 ubiquitin ligase is capable of decreasing the surface level of the membrane-bound protein upon forced dimerization, preferably by ubiquitination of the membrane-bound protein. The method of the invention comprises a step of exposing a cell to a heterobifunctional molecule, wherein the heterobifunctional molecule comprises a first binding domain capable of specific binding to an extracellular portion of the transmembrane E3 ubiquitin ligase, and a second binding domain capable of specific binding to an extracellular portion of the membrane-bound protein. The method further comprises a step of determining the decrease in surface level of the membrane-bound protein. The invention additionally pertains to a heterobifunctional molecule targeting an effective combination of a transmembrane E3 ubiquitin ligase and a membrane-bound protein.

The present disclosure is drawn to HCMV US11 based therapeutics that can be used to target and reduce the activity of the FcRn protein. The disclosure provides a method of treating auto-immune mediated and albumin-mediated diseases in a subject comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising HCMV US11 (herein after referred to as “US11”) polypeptide, polypeptide fragments, or variants thereof. The disclosure also provides methods for preventing, or treating, infections of HCMV through administration of a US11 inhibitor. US11 containing vaccine compositions are also provided for stimulation of an anti-US11 immune response for protection against HCMV infection.

The present invention provides compounds, compositions thereof, and methods of using the same.