|
|
|
|
| LEADER |
01000caa a22002652 4500 |
| 001 |
NLM270770291 |
| 003 |
DE-627 |
| 005 |
20240610235705.0 |
| 007 |
cr uuu---uuuuu |
| 008 |
231224s2017 xx |||||o 00| ||eng c |
| 024 |
7 |
|
|a 10.1016/j.clim.2017.03.014
|2 doi
|
| 028 |
5 |
2 |
|a pubmed24n1436.xml
|
| 035 |
|
|
|a (DE-627)NLM270770291
|
| 035 |
|
|
|a (NLM)28389388
|
| 035 |
|
|
|a (PII)S1521-6616(16)30620-9
|
| 040 |
|
|
|a DE-627
|b ger
|c DE-627
|e rakwb
|
| 041 |
|
|
|a eng
|
| 100 |
1 |
|
|a Tanner, Mark R
|e verfasserin
|4 aut
|
| 245 |
1 |
0 |
|a Prolonged immunomodulation in inflammatory arthritis using the selective Kv1.3 channel blocker HsTX1[R14A] and its PEGylated analog
|
| 264 |
|
1 |
|c 2017
|
| 336 |
|
|
|a Text
|b txt
|2 rdacontent
|
| 337 |
|
|
|a ƒaComputermedien
|b c
|2 rdamedia
|
| 338 |
|
|
|a ƒa Online-Ressource
|b cr
|2 rdacarrier
|
| 500 |
|
|
|a Date Completed 29.08.2017
|
| 500 |
|
|
|a Date Revised 10.06.2024
|
| 500 |
|
|
|a published: Print-Electronic
|
| 500 |
|
|
|a Citation Status MEDLINE
|
| 520 |
|
|
|a Copyright © 2017 Elsevier Inc. All rights reserved.
|
| 520 |
|
|
|a Effector memory T lymphocytes (TEM cells) that lack expression of CCR7 are major drivers of inflammation in a number of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. The Kv1.3 potassium channel is a key regulator of CCR7- TEM cell activation. Blocking Kv1.3 inhibits TEM cell activation and attenuates inflammation in autoimmunity, and as such, Kv1.3 has emerged as a promising target for the treatment of TEM cell-mediated autoimmune diseases. The scorpion venom-derived peptide HsTX1 and its analog HsTX1[R14A] are potent Kv1.3 blockers and HsTX1[R14A] is selective for Kv1.3 over closely-related Kv1 channels. PEGylation of HsTX1[R14A] to create a Kv1.3 blocker with a long circulating half-life reduced its affinity but not its selectivity for Kv1.3, dramatically reduced its adsorption to inert surfaces, and enhanced its circulating half-life in rats. PEG-HsTX1[R14A] is equipotent to HsTX1[R14A] in preferential inhibition of human and rat CCR7- TEM cell proliferation, leaving CCR7+ naïve and central memory T cells able to proliferate. It reduced inflammation in an active delayed-type hypersensitivity model and in the pristane-induced arthritis (PIA) model of rheumatoid arthritis (RA). Importantly, a single subcutaneous dose of PEG-HsTX1[R14A] reduced inflammation in PIA for a longer period of time than the non-PEGylated HsTX1[R14A]. Together, these data indicate that HsTX1[R14A] and PEG-HsTX1[R14A] are effective in a model of RA and are therefore potential therapeutics for TEM cell-mediated autoimmune diseases. PEG-HsTX1[R14A] has the additional advantages of reduced non-specific adsorption to inert surfaces and enhanced circulating half-life
|
| 650 |
|
4 |
|a Journal Article
|
| 650 |
|
4 |
|a Disulfide rich peptide
|
| 650 |
|
4 |
|a Effector memory T lymphocyte
|
| 650 |
|
4 |
|a Immunomodulation
|
| 650 |
|
4 |
|a KCNA3
|
| 650 |
|
4 |
|a PEGylated Kv1.3 blocker
|
| 650 |
|
4 |
|a Voltage-gated channel
|
| 650 |
|
7 |
|a Allergens
|2 NLM
|
| 650 |
|
7 |
|a Kv1.3 Potassium Channel
|2 NLM
|
| 650 |
|
7 |
|a Peptides
|2 NLM
|
| 650 |
|
7 |
|a Potassium Channel Blockers
|2 NLM
|
| 650 |
|
7 |
|a Scorpion Venoms
|2 NLM
|
| 650 |
|
7 |
|a TX1 toxin, Heterometrus spinnifer
|2 NLM
|
| 650 |
|
7 |
|a Terpenes
|2 NLM
|
| 650 |
|
7 |
|a pristane
|2 NLM
|
| 650 |
|
7 |
|a 26HZV48DT1
|2 NLM
|
| 650 |
|
7 |
|a Polyethylene Glycols
|2 NLM
|
| 650 |
|
7 |
|a 3WJQ0SDW1A
|2 NLM
|
| 650 |
|
7 |
|a Ovalbumin
|2 NLM
|
| 650 |
|
7 |
|a 9006-59-1
|2 NLM
|
| 700 |
1 |
|
|a Tajhya, Rajeev B
|e verfasserin
|4 aut
|
| 700 |
1 |
|
|a Huq, Redwan
|e verfasserin
|4 aut
|
| 700 |
1 |
|
|a Gehrmann, Elizabeth J
|e verfasserin
|4 aut
|
| 700 |
1 |
|
|a Rodarte, Kathia E
|e verfasserin
|4 aut
|
| 700 |
1 |
|
|a Atik, Mustafa A
|e verfasserin
|4 aut
|
| 700 |
1 |
|
|a Norton, Raymond S
|e verfasserin
|4 aut
|
| 700 |
1 |
|
|a Pennington, Michael W
|e verfasserin
|4 aut
|
| 700 |
1 |
|
|a Beeton, Christine
|e verfasserin
|4 aut
|
| 773 |
0 |
8 |
|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 180(2017) vom: 15. Juli, Seite 45-57
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnns
|
| 773 |
1 |
8 |
|g volume:180
|g year:2017
|g day:15
|g month:07
|g pages:45-57
|
| 856 |
4 |
0 |
|u http://dx.doi.org/10.1016/j.clim.2017.03.014
|3 Volltext
|
| 912 |
|
|
|a GBV_USEFLAG_A
|
| 912 |
|
|
|a SYSFLAG_A
|
| 912 |
|
|
|a GBV_NLM
|
| 912 |
|
|
|a GBV_ILN_11
|
| 912 |
|
|
|a GBV_ILN_24
|
| 912 |
|
|
|a GBV_ILN_350
|
| 951 |
|
|
|a AR
|
| 952 |
|
|
|d 180
|j 2017
|b 15
|c 07
|h 45-57
|