Title:
NERVE CELL ACTIVATOR
Document Type and Number:
WIPO Patent Application WO/2022/080473
Kind Code:
A1
Abstract:
The present inventors found that the indolinone compound of the present invention has excellent effect of activating nerve cells. The present inventors further found that the function mechanism of the effect of activating nerve cells is based on the promotion of the expression of a protein that relates to the BDNF signaling system and/or the VEGF signaling system. Thus, the indolinone compound of the present invention is usable as a therapeutic agent for various neuropsychiatric diseases. Moreover, this compound can protect transplanted neural progenitor cells and, therefore, is usable as an adjunct in regenerative medicine. The present inventors established a method for inducing the differentiation of induced pluripotent stem cells (iPS cells) into nerve cells at a high efficiency without through the formation of an embryonic body (cell aggregate) in a xeno-free culture system. By this method, nerve cells, which contained no factor derived from a different organism, were affected neither by unidentified components nor by interlot differences and had characteristics of a disease patient, were successfully prepared. As a result, it becomes possible to stably screen and analyze a compound for the treatment of a neurological disease for drug discovery.
Inventors:
MISAWA YUKIKO (JP)
Application Number:
PCT/JP2021/038149
Publication Date:
April 21, 2022
Filing Date:
October 14, 2021
Export Citation:
Assignee:
MISAWA YUKIKO (JP)
International Classes:
A61K31/404; A61K35/30; A61L27/36; A61L27/38; A61P9/10; A61P25/00; A61P25/04; A61P25/14; A61P25/16; A61P25/18; A61P25/22; A61P25/24; A61P25/28; A61P43/00; C12N5/074; C12N5/0793; C12N5/10; C12N15/12
Domestic Patent References:
| WO2018155620A1 | 2018-08-30 |
Foreign References:
| JPH0272158A | 1990-03-12 |
Other References:
GRAMMAS PAULA, MARTINEZ JOSEPH, SANCHEZ ALMA, YIN XIANGLING, RILEY JARRED, GAY DYLAN, DESOBRY KATHERINE, TRIPATHY DEBJANI, LUO JIN: "A New Paradigm for the Treatment of Alzheimer's Disease: Targeting Vascular Activation", JOURNAL OF ALZHEIMER`S DISEASE, vol. 40, no. 3, 23 April 2014 (2014-04-23), NL , pages 619 - 630, XP009535776, ISSN: 1387-2877, DOI: 10.3233/JAD-2014-132057
BURGER, S. ; YAFAI, Y. ; BIGL, M. ; WIEDEMANN, P. ; SCHLIEBS, R.: "Effect of VEGF and its receptor antagonist SU-5416, an inhibitor of angiogenesis, on processing of the @b-amyloid precursor protein in primary neuronal cells derived from brain tissue of Tg2576 mice", INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE., PERGAMON, OXFORD., GB, vol. 28, no. 7, 1 November 2010 (2010-11-01), GB , pages 597 - 604, XP027279033, ISSN: 0736-5748
HOFF P M ET AL: "A phase I study of escalating doses of the tyrosine kinase inhibitor semaxanib (SU5416) in combination with irinotecan in patients with advanced colorectal carcinoma", JAPANESE JOURNAL OF CLINICAL ONCOLOGY, TOKYO., JP, vol. 36, no. 2, 1 January 2006 (2006-01-01), JP , pages 100 - 103, XP008087904, ISSN: 0368-2811, DOI: 10.1093/jjco/hyi229
TANIGUCHI, YUKIMASA ET AL.: "Development of Cell Culture Substrate for Regenerative Treatments", BIOTECHNOLOGY, vol. 96, no. 6, 2018, pages 328 - 332, XP009526754
NAKAZAWA, TAKANOBU; RYOTA, HASHIMOTO: "Investigation into Molecular Cell Substrates in Nerve Cells of Patients with Schizophrenia", ANNUAL BUSINESS REPORT, vol. 58, 1 January 2017 (2017-01-01), JP, pages 78 - 79, XP009535777
BURGER, S. ; YAFAI, Y. ; BIGL, M. ; WIEDEMANN, P. ; SCHLIEBS, R.: "Effect of VEGF and its receptor antagonist SU-5416, an inhibitor of angiogenesis, on processing of the @b-amyloid precursor protein in primary neuronal cells derived from brain tissue of Tg2576 mice", INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE., PERGAMON, OXFORD., GB, vol. 28, no. 7, 1 November 2010 (2010-11-01), GB , pages 597 - 604, XP027279033, ISSN: 0736-5748
HOFF P M ET AL: "A phase I study of escalating doses of the tyrosine kinase inhibitor semaxanib (SU5416) in combination with irinotecan in patients with advanced colorectal carcinoma", JAPANESE JOURNAL OF CLINICAL ONCOLOGY, TOKYO., JP, vol. 36, no. 2, 1 January 2006 (2006-01-01), JP , pages 100 - 103, XP008087904, ISSN: 0368-2811, DOI: 10.1093/jjco/hyi229
TANIGUCHI, YUKIMASA ET AL.: "Development of Cell Culture Substrate for Regenerative Treatments", BIOTECHNOLOGY, vol. 96, no. 6, 2018, pages 328 - 332, XP009526754
NAKAZAWA, TAKANOBU; RYOTA, HASHIMOTO: "Investigation into Molecular Cell Substrates in Nerve Cells of Patients with Schizophrenia", ANNUAL BUSINESS REPORT, vol. 58, 1 January 2017 (2017-01-01), JP, pages 78 - 79, XP009535777
Attorney, Agent or Firm:
TADA Eiko et al. (JP)
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