# US 9,243,281 B2 · Neuroprotective chemicals and methods for identifying and using same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,243,281 B2 - Document ID: US9243281B2 - Status: Granted - Kind: B2 - Application number: 14/540,006 - Filed: 2014-11-12 - Published: 2015-05-14 - Granted: 2016-01-26 - Earliest claimed: 2013-11-11 - Assignees: Board of Regents, The University of Texas System - Applicants: Board of Regents of The University of Texas System - Inventors: Steven L. McKnight; Joseph M. Ready; Andrew A. Pieper; Gelin Wang; Ting Han - Web page: https://patentgrep.com/patent/US9243281B2 ## CPC - G01N 33/5058: {Neurological cells} - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - C12Q 1/48: involving transferase - G01N 33/5014: {for testing toxicity} - G01N 33/5038: {involving detection of metabolites per se} - G01N 2333/91142: Pentosyltransferases (2.4.2) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES ## Abstract Provided herein are methods for identifying a compound having cell-protective (e.g., neuroprotective) activity. Compounds identified therefrom are also provided. These compounds can be used to treat various diseases, disorders, or conditions associated with, for example, unwanted cell death. ## Claims ### Claim 1 A method for identifying a compound having cell-protective activity, comprising: exposing a population of cells to a test compound and a DNA-damaging agent; determining survival rate of the population of cells; wherein an increase in the survival rate compared to a control that is not treated with the test compound is indicative of cell-protective activity of the test compound; and incubating the test compound with nicotinamide phosphoribosyltransferase (NAMPT) and measuring an activity of the NAMPT, wherein an increase in the activity of the NAMPT additionally confirms the cell-protective activity of the test compound. ### Claim 2 (depends on 1) The method of claim 1, wherein the exposing step comprises incubating the population of cells with the test compound and the DNA-damaging agent. ### Claim 3 (depends on 1) The method of claim 1, wherein the exposing step comprises incubating the population of cells with the test compound first, followed by the DNA-damaging agent. ### Claim 4 (depends on 1) The method of claim 1, wherein the exposing step comprises incubating the population of cells with the DNA-damaging agent first, followed by the test compound. ### Claim 5 (depends on 1) The method of claim 1, wherein the DNA-damaging agent activates poly-ADP-ribose polymerase (PARP). ### Claim 6 (depends on 5) The method of claim 5, wherein the DNA-damaging agent leads to decline in nicotinamide adenine dinucleotide (NAD) level. ### Claim 7 (depends on 1) The method of claim 1, wherein the DNA-damaging agent is an anthracycline. ### Claim 8 (depends on 7) The method of claim 7, wherein the anthracycline is one or more of daunorubicin, doxorubicin, epirubicin, idarubicin, valrubicin and mitoxantrone. ### Claim 9 (depends on 8) The method of claim 8, wherein the anthracycline is doxorubicin. ### Claim 10 (depends on 1) The method of claim 1, wherein the cells are mammalian cells. ### Claim 11 (depends on 1) The method of claim 1, wherein the test compound is provided at about 1-20 uM, or about 2-10 uM or about 5 uM. ### Claim 12 (depends on 1) The method of claim 1, wherein the test compound is a small molecule. ### Claim 13 (depends on 1) The method of claim 1, wherein the DNA-damaging agent is provided at about 0.01-20 uM, or about 0.05-10 uM, or about 0.1-1.5 uM, or about 0.5 uM. ### Claim 14 (depends on 1) The method of claim 1, further comprising determining the test compound having said cell-protective activity protects the cells from toxicity mediated by the DNA-damaging agent. ### Claim 15 (depends on 1) The method of claim 1, further comprising determining the test compound having said cell-protective activity does not protect the cells from toxicity induced by a toxin selected from the group consisting of bortezomib, staurosporine, taxol, brefeldin, cytochalasin D, TNFa and TRAIL. ### Claim 16 (depends on 12) The method of claim 12, further comprising determining the test compound having said cell-protective activity increases nicotinamide adenine dinucleotide (NAD) level. ### Claim 17 (depends on 1) The method of claim 1, further comprising determining the test compound having said cell-protective activity binds and/or activates the NAMPT. ### Claim 18 (depends on 1) The method of claim 1, wherein the cell-protective activity is neuroprotective activity which includes one or more of: promoting survival, health, integrity, growth, development and/or function of neurons, protecting neurons from cell death, apoptosis and/or degeneration, and stimulating neurogenesis.