Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits

Wenhui Hu; Hantamalala Ralay Ranaivo; Saktimayee M. Roy; Heather A. Behanna; Laura K. Wing; Lenka Munoz; Ling Guo; Linda J. Van Eldik; D. Martin Watterson

doi:10.1016/j.bmcl.2006.10.028

Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits

Wenhui Hu, Hantamalala Ralay Ranaivo, Saktimayee M. Roy, Heather A. Behanna, Laura K. Wing, Lenka Munoz, Ling Guo, Linda J. Van Eldik, D. Martin Watterson

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

We report the development of a novel, aqueous-soluble, safe, small molecule, experimental therapeutic that suppresses injury-induced, proinflammatory cytokine increases in the brain, with resultant attenuation of synaptic protein biomarker loss and improvement in hippocampus-dependent behavioral deficits. A GMP production scheme for the active pharmaceutical ingredient, compound 17, is presented. The development and large-scale availability of this novel compound allow exploration of new, potentially disease-modifying, therapeutic approaches to CNS disorders.

Original language	English
Pages (from-to)	414-418
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2006.10.028
State	Published - Jan 15 2007

Bibliographical note

Funding Information:
This work was supported in part by NIH Grants AG028561, NS047586, and AG000260.

Funding

This work was supported in part by NIH Grants AG028561, NS047586, and AG000260.

Funders	Funder number
National Institutes of Health (NIH)	NS047586, AG028561
National Institute on Aging	T32AG000260

Keywords

Alzheimer's disease
Neurodegeneration
Process chemistry
Proinflammatory cytokine
Pyridazine

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2006.10.028

Cite this

Hu, W., Ralay Ranaivo, H., Roy, S. M., Behanna, H. A., Wing, L. K., Munoz, L., Guo, L., Van Eldik, L. J., & Watterson, D. M. (2007). Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits. Bioorganic and Medicinal Chemistry Letters, 17(2), 414-418. https://doi.org/10.1016/j.bmcl.2006.10.028

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abstract = "We report the development of a novel, aqueous-soluble, safe, small molecule, experimental therapeutic that suppresses injury-induced, proinflammatory cytokine increases in the brain, with resultant attenuation of synaptic protein biomarker loss and improvement in hippocampus-dependent behavioral deficits. A GMP production scheme for the active pharmaceutical ingredient, compound 17, is presented. The development and large-scale availability of this novel compound allow exploration of new, potentially disease-modifying, therapeutic approaches to CNS disorders.",

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note = "Funding Information: This work was supported in part by NIH Grants AG028561, NS047586, and AG000260. ",

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doi = "10.1016/j.bmcl.2006.10.028",

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Hu, W, Ralay Ranaivo, H, Roy, SM, Behanna, HA, Wing, LK, Munoz, L, Guo, L, Van Eldik, LJ & Watterson, DM 2007, 'Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits', Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 2, pp. 414-418. https://doi.org/10.1016/j.bmcl.2006.10.028

Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits. / Hu, Wenhui; Ralay Ranaivo, Hantamalala; Roy, Saktimayee M. et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 2, 15.01.2007, p. 414-418.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits

AU - Hu, Wenhui

AU - Ralay Ranaivo, Hantamalala

AU - Roy, Saktimayee M.

AU - Behanna, Heather A.

AU - Wing, Laura K.

AU - Munoz, Lenka

AU - Guo, Ling

AU - Van Eldik, Linda J.

AU - Watterson, D. Martin

N1 - Funding Information: This work was supported in part by NIH Grants AG028561, NS047586, and AG000260.

PY - 2007/1/15

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N2 - We report the development of a novel, aqueous-soluble, safe, small molecule, experimental therapeutic that suppresses injury-induced, proinflammatory cytokine increases in the brain, with resultant attenuation of synaptic protein biomarker loss and improvement in hippocampus-dependent behavioral deficits. A GMP production scheme for the active pharmaceutical ingredient, compound 17, is presented. The development and large-scale availability of this novel compound allow exploration of new, potentially disease-modifying, therapeutic approaches to CNS disorders.

AB - We report the development of a novel, aqueous-soluble, safe, small molecule, experimental therapeutic that suppresses injury-induced, proinflammatory cytokine increases in the brain, with resultant attenuation of synaptic protein biomarker loss and improvement in hippocampus-dependent behavioral deficits. A GMP production scheme for the active pharmaceutical ingredient, compound 17, is presented. The development and large-scale availability of this novel compound allow exploration of new, potentially disease-modifying, therapeutic approaches to CNS disorders.

KW - Alzheimer's disease

KW - Neurodegeneration

KW - Process chemistry

KW - Proinflammatory cytokine

KW - Pyridazine

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JO - Bioorganic and Medicinal Chemistry Letters

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Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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