biostudies-literatureTarcha EJNIAID NIH HHSNINDS NIH HHS642-53https://www.ebi.ac.uk/biostudies/studies/S-EPMC3422530biostudies-literatureUnknown342(3)The Kv1.3 channel is a recognized target for pharmaceutical development to treat autoimmune diseases and organ rejection. ShK-186, a specific peptide inhibitor of Kv1.3, has shown promise in animal models of multiple sclerosis and rheumatoid arthritis. Here, we describe the pharmacokinetic-pharmacodynamic relationship for ShK-186 in rats and monkeys. The pharmacokinetic profile of ShK-186 was evaluated with a validated high-performance liquid chromatography-tandem mass spectrometry method to measure the peptide's concentration in plasma. These results were compared with single-photon emission computed tomography/computed tomography data collected with an ¹¹¹In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugate of ShK-186 to assess whole-blood pharmacokinetic parameters as wThe Journal of pharmacology and experimental therapeuticsDurable pharmacological responses from the peptide ShK-186, a specific Kv1.3 channel inhibitor that suppresses T cell mediators of autoimmune disease.PMC3422530R01 NS048252R43-AI085691R43 AI085691R01-NS48252Bailey DSlauter RNorton KMunoz-Elias EJTjong IHu XBeeton CHansen ZTarcha EJBoley SESams JNguyen HRuppert GWKnapp BUpadhyay SKPennington MWKentala DChandy KGBanks AChi VIadonato SPLondono LMfalseDurable pharmacological responses from the peptide ShK-186, a specific Kv1.3 channel inhibitor that suppresses T cell mediators of autoimmune disease.The Kv1.3 channel is a recognized target for pharmaceutical development to treat autoimmune diseases and organ rejection. ShK-186, a specific peptide inhibitor of Kv1.3, has shown promise in animal models of multiple sclerosis and rheumatoid arthritis. Here, we describe the pharmacokinetic-pharmacodynamic relationship for ShK-186 in rats and monkeys. The pharmacokinetic profile of ShK-186 was evaluated with a validated high-performance liquid chromatography-tandem mass spectrometry method to measure the peptide's concentration in plasma. These results were compared with single-photon emission computed tomography/computed tomography data collected with an ¹¹¹In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugate of ShK-186 to assess whole-blood pharmacokinetic parameters as w2012-01-01T00:00:00Z2012 Sep2026-05-04T00:57:08.385Z2019-03-27T00:57:00ZS-EPMC34225302263772410.1124/jpet.112.191890