Abstract: Provided herein are methods and compositions for inhibiting p97, for the treatment of a cancer in a subject, or a symptom thereof. Upon treatment, the cancer, or a symptom thereof is reduced in the subject. Additionally, methods for measuring sensitivity of a subject to p97 inhibition, methods of assessing a pharmaceutical agent for p97 inhibition activity, and methods of assessing the effect of a pharmaceutical agent for p97 inhibition activity in a subject are provided herein.

Abstract: Provided herein are methods and compositions for inhibiting p97, for the treatment of a motor neuron disease in a subject, or a symptom thereof. Upon treatment, the motor neuron disease, or a symptom thereof is reduced in the subject.

Abstract: Provided herein are methods and compositions for inhibiting p97, for the treatment of a coronavirus infection in a subject, or a symptom thereof. Upon treatment, the coronavirus infection, or a symptom thereof is reduced in the subject.

Abstract: The present disclosure relates generally to methods for treating multisystem degenerative diseases, hematological malignancies, solid tumors, and neurodegenerative disorders.

Abstract: The present disclosure relates to compositions and methods for treating Sanfilippo syndrome (also known as Sanfilippo disease type D, Sanfilippo D, mucopolysaccharidosis type IIID, MPS IIID). The method can entail injecting to the spinal fluid of a MPS IIID patient an effective amount of a composition comprising a recombinant human acetylglucosamine-6-sulfatase (GNS) protein comprising the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1 and having the enzymatic activity of the human GNS protein. The composition can be provided in an artificial cerebrospinal fluid. About 1 mg to about 100 mg of the recombinant polypeptide may be administered to the patient once every 2 weeks to 6 months.

Abstract: The present disclosure relates generally to methods for treating multisystem degenerative diseases, hematological malignancies, solid tumors, and neurodegenerative disorders.

Abstract: The present disclosure relates to compositions and methods for treating Sanfilippo syndrome (also known as Sanfilippo disease type D, Sanfilippo D, mucopolysaccharidosis type IIID, MPS IIID). The method can entail injecting to the spinal fluid of a MPS IIID patient an effective amount of a composition comprising a recombinant human acetylglucosamine-6-sulfatase (GNS) protein comprising the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1 and having the enzymatic activity of the human GNS protein. The composition can be provided in an artificial cerebrospinal fluid. About 1 mg to about 100 mg of the recombinant polypeptide may be administered to the patient once every 2 weeks to 6 months.

Abstract: One aspect of the invention relates to compounds that inhibit the activity of p97, such as by binding covalently to a cysteine residue in the active site. In certain embodiments, the invention relates to the treatment of disease, such as cancer, comprising administering a compound of the invention.

Abstract: Compounds of Formulas I-XLIII are identified as direct inhibitors of p97 ATPase or of the degradation of a p97-dependent ubiquitin-proteasome system (UPS) substrate. Methods and compositions are disclosed for inhibiting p97 ATPase and the degradation of a p97-dependent UPS substrate, and for identifying inhibitors thereof.

Abstract: Compounds of Formulas I-XLIII are identified as direct inhibitors of p97 ATPase or of the degradation of a p97-dependent ubiquitin-proteasome system (UPS) substrate.

Abstract: One aspect of the invention relates to compounds that inhibit the activity of p97, such as by binding covalently to a cysteine residue in the active site. In certain embodiments, the invention relates to the treatment of disease, such as cancer, comprising administering a compound of the invention.