Discovery of a Stress-Activated Protein Kinase Inhibitor for Lymphatic Filariasis

Sreedhar R. Tummalapalli, Rohit Bhat, Agnieszka Chojnowski, Monika Prorok, Tamara Kreiss, Ronald Goldberg, Stacie Canan, Natalie Hawryluk, Deborah Mortensen, Vikram Khetani, Jerome Zeldis, John Siekierka, David Rotella

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Lymphatic filariasis infects over 120 million people worldwide and can lead to significant disfigurement and disease. Resistance is emerging with current treatments, and these therapies have dose limiting adverse events; consequently new targets are needed. One approach to achieve this goal is inhibition of parasitic protein kinases involved in circumventing host defense mechanisms. This report describes structure-activity relationships leading to the identification of a potent, orally bioavailable stress activated protein kinase inhibitor that may be used to investigate this hypothesis.

Original languageEnglish
Pages (from-to)210-214
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume9
Issue number3
DOIs
StatePublished - 8 Mar 2018

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Filarial Elephantiasis
Structure-Activity Relationship
Protein Kinase Inhibitors
Heat-Shock Proteins
Protein Kinases
Therapeutics

Keywords

  • Parasitic kinase inhibitor
  • lymphatic filariasis
  • stress-activated kinase

Cite this

Tummalapalli, Sreedhar R. ; Bhat, Rohit ; Chojnowski, Agnieszka ; Prorok, Monika ; Kreiss, Tamara ; Goldberg, Ronald ; Canan, Stacie ; Hawryluk, Natalie ; Mortensen, Deborah ; Khetani, Vikram ; Zeldis, Jerome ; Siekierka, John ; Rotella, David. / Discovery of a Stress-Activated Protein Kinase Inhibitor for Lymphatic Filariasis. In: ACS Medicinal Chemistry Letters. 2018 ; Vol. 9, No. 3. pp. 210-214.
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Tummalapalli, SR, Bhat, R, Chojnowski, A, Prorok, M, Kreiss, T, Goldberg, R, Canan, S, Hawryluk, N, Mortensen, D, Khetani, V, Zeldis, J, Siekierka, J & Rotella, D 2018, 'Discovery of a Stress-Activated Protein Kinase Inhibitor for Lymphatic Filariasis', ACS Medicinal Chemistry Letters, vol. 9, no. 3, pp. 210-214. https://doi.org/10.1021/acsmedchemlett.7b00477

Discovery of a Stress-Activated Protein Kinase Inhibitor for Lymphatic Filariasis. / Tummalapalli, Sreedhar R.; Bhat, Rohit; Chojnowski, Agnieszka; Prorok, Monika; Kreiss, Tamara; Goldberg, Ronald; Canan, Stacie; Hawryluk, Natalie; Mortensen, Deborah; Khetani, Vikram; Zeldis, Jerome; Siekierka, John; Rotella, David.

In: ACS Medicinal Chemistry Letters, Vol. 9, No. 3, 08.03.2018, p. 210-214.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Prorok, Monika

AU - Kreiss, Tamara

AU - Goldberg, Ronald

AU - Canan, Stacie

AU - Hawryluk, Natalie

AU - Mortensen, Deborah

AU - Khetani, Vikram

AU - Zeldis, Jerome

AU - Siekierka, John

AU - Rotella, David

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Tummalapalli SR, Bhat R, Chojnowski A, Prorok M, Kreiss T, Goldberg R et al. Discovery of a Stress-Activated Protein Kinase Inhibitor for Lymphatic Filariasis. ACS Medicinal Chemistry Letters. 2018 Mar 8;9(3):210-214. https://doi.org/10.1021/acsmedchemlett.7b00477