SG11201804440XA - Chemical reprogramming of human glial cells into neurons with small molecule cocktail - Google Patents

Chemical reprogramming of human glial cells into neurons with small molecule cocktail

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Publication number
SG11201804440XA
SG11201804440XA SG11201804440XA SG11201804440XA SG11201804440XA SG 11201804440X A SG11201804440X A SG 11201804440XA SG 11201804440X A SG11201804440X A SG 11201804440XA SG 11201804440X A SG11201804440X A SG 11201804440XA SG 11201804440X A SG11201804440X A SG 11201804440XA
Authority
SG
Singapore
Prior art keywords
international
drive
neurons
glial cells
state
Prior art date
Application number
SG11201804440XA
Inventor
Gong Chen
Lei Zhang
Jiuchao Yin
Ningxin Ma
Original Assignee
Penn State Res Found
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Penn State Res Found filed Critical Penn State Res Found
Publication of SG11201804440XA publication Critical patent/SG11201804440XA/en

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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0618—Cells of the nervous system
    • C12N5/0619—Neurons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A61P25/12—Antiepileptics; Anticonvulsants for grand-mal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/05—Inorganic components
    • C12N2500/10—Metals; Metal chelators
    • C12N2500/12—Light metals, i.e. alkali, alkaline earth, Be, Al, Mg
    • C—CHEMISTRY; METALLURGY
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    • C12N2500/38—Vitamins
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    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/02—Compounds of the arachidonic acid pathway, e.g. prostaglandins, leukotrienes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
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    • C12N2501/15—Transforming growth factor beta (TGF-β)
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    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/40—Regulators of development
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    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/70—Enzymes
    • C12N2501/72—Transferases (EC 2.)
    • C12N2501/727—Kinases (EC 2.7.)
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    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/999—Small molecules not provided for elsewhere
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    • C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
    • C12N2506/08—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from cells of the nervous system

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
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  • Zoology (AREA)
  • Wood Science & Technology (AREA)
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  • Biochemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Pain & Pain Management (AREA)
  • Toxicology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property -' Organization International Bureau (43) International Publication Date .... ....r .„,„1 8 June 2017 (08.06.2017) W I P0 1 PCT ID Hit (10) WO International 2017/096123 111111111111111111IIIIII111111111111111111111111111111111111MIIIIIIIIIIIIIII Publication Number Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61P 35/00 (2006.01) A61K 31/4545 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, PCT/US2016/064553 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 2 December 2016 (02.12.2016) KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (25) Filing Language: English OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (26) Publication Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (30) Priority Data: ZW. 62/263,353 4 December 2015 (04.12.2015) US (84) Designated States (unless otherwise indicated, for every (71) Applicant: THE PENN STATE RESEARCH FOUND- kind of regional protection available): ARIPO (BW, GH, ATION [US/US]; 304 Old Main, University Park, PA GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 16802-7000 (US). TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (72) Inventors: CHEN, Gong; 2354 Autumnwood Drive, State TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, College, PA 16801 (US) ZHANG, Lei; 425 Waupelani DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, L Drive, Apt. 318, State College, PA 16801 (US). YIN, V, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, Jiuchao; 425 Waupelani Drive, Apt. N16, State College, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, PA 16801 (US). MA, Ningxin; 425 Waupelani Drive, Apt. GW, KM, ML, MR, NE, SN, TD, TG). 508, State College, PA 16801 (US). Published: 21(3)) (74) Agents: WATT, Rachel S. et al.; Hodgson Russ LLP, The — with international search report (Art Guaranty Building, 140 Pearl Street, Suite 100, Buffalo, NY 14202-4040 (US). 1-1 .4t M ei 1-1 ct\ O ir.., (54) Title: CHEMICAL REPROGRAMMING OF HUMAN GLIAL CELLS INTO NEURONS WITH SMALL MOLECULE Il COCKTAIL 0 ei (57) : Provided are compositions, articles and methods that relate to promoting neurogenesis or neuroregeneration in mam- a)malian nervous system. Embodiments relate to use of groups of compounds that contain Crizotinib (Cri), Flurbiprofen, Lithium Chloride (Li), Vitamin C (VC), Ceritinib (Cer) or Pirfenidone (PFD). In certain implementations glial cells are converted into func - 5 tional neurons.
SG11201804440XA 2015-12-04 2016-12-02 Chemical reprogramming of human glial cells into neurons with small molecule cocktail SG11201804440XA (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562263353P 2015-12-04 2015-12-04
PCT/US2016/064553 WO2017096123A1 (en) 2015-12-04 2016-12-02 Chemical reprogramming of human glial cells into neurons with small molecule cocktail

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SG11201804440XA true SG11201804440XA (en) 2018-06-28

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US (2) US9885015B2 (en)
EP (2) EP3795147B1 (en)
JP (1) JP6951336B2 (en)
KR (2) KR102102837B1 (en)
CN (2) CN111184739B (en)
AU (1) AU2016364845B2 (en)
CA (1) CA3007116A1 (en)
HK (1) HK1256307A1 (en)
SG (1) SG11201804440XA (en)
WO (1) WO2017096123A1 (en)

Cited By (1)

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Publication number Priority date Publication date Assignee Title
CN113244236A (en) * 2021-06-01 2021-08-13 上海市第一人民医院 Application of ceritinib in preparation of medicine for treating thyroid-associated ophthalmopathy

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IT201800001168A1 (en) * 2018-01-17 2019-07-17 Fond Per Listituto Oncologico Di Ricerca Ior NEW SENOLYTIC DRUGS INHIBITORS ALK
US20220193114A1 (en) * 2019-04-18 2022-06-23 Brown University Neurogenesis
AU2020392124A1 (en) * 2019-11-25 2022-06-16 The Penn State Research Foundation Composition and method for converting human glial cells into neurons
WO2021195706A1 (en) * 2020-03-31 2021-10-07 Children's Medical Research Institute New dynamin inhibitors and uses
WO2022095057A1 (en) * 2020-11-09 2022-05-12 深圳先进技术研究院 Pharmaceutical composition and medical use thereof

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BR0012327A (en) * 1999-07-09 2002-07-02 Ortho Mcneil Pharm Inc Neurotrophic pyrrolidines and piperidines, and related compositions and methods
GB0316882D0 (en) * 2003-07-18 2003-08-20 Consejo Superior Investigacion Reversible immortalization of OEG from human olfactory bulbs as a tool to promote spinal cord regeneration
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CN101732255A (en) 2010-01-07 2010-06-16 同济大学 Flurbiprofen liposome and preparation method thereof
EP3578988A1 (en) * 2010-05-25 2019-12-11 Memorial Sloan-Kettering Cancer Center Method of nociceptor differentiantion of human embryonic stem cells and uses thereof
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Publication number Priority date Publication date Assignee Title
CN113244236A (en) * 2021-06-01 2021-08-13 上海市第一人民医院 Application of ceritinib in preparation of medicine for treating thyroid-associated ophthalmopathy

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AU2016364845B2 (en) 2022-07-28
KR20200043503A (en) 2020-04-27
CA3007116A1 (en) 2017-06-08
KR102102837B1 (en) 2020-04-22
JP2018535988A (en) 2018-12-06
EP3795147A1 (en) 2021-03-24
KR102444438B1 (en) 2022-09-19
AU2016364845A1 (en) 2018-06-21
WO2017096123A1 (en) 2017-06-08
US20180148688A1 (en) 2018-05-31
JP6951336B2 (en) 2021-10-20
EP3795147B1 (en) 2023-08-30
CN108430582A (en) 2018-08-21
CN111184739B (en) 2022-06-24
CN111184739A (en) 2020-05-22
CN108430582B (en) 2020-02-21
HK1256307A1 (en) 2019-09-20
KR20180081824A (en) 2018-07-17
EP3383495A4 (en) 2019-09-04
US20170159013A1 (en) 2017-06-08
US9885015B2 (en) 2018-02-06
EP3383495A1 (en) 2018-10-10
US10253293B2 (en) 2019-04-09
EP3383495B1 (en) 2021-01-20

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