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hERG1a/1b channels are less sensitive to ITP‐2. (A) Family of current traces showing reduced sensitivity of hERG1a/1b channels to ITP‐2. Currents were elicited as in Figure 1A. (B, C) Corresponding current–voltage relationships for hERG1a/1b steady‐state currents and tail currents before and after 3 μM ITP‐2. ITP‐2 selectively increases test pulse currents, similar to hERG1a channels. Data shown are means±SEM; n = 5. *P < 0.05; significantly different from control; two‐way ANOVA. (D, E) Bar graphs showing reduced sensitivity of hERG1a/1b channels to ITP‐2 (nearly sixfold); n = 13 for hERG1a; n = 8 for hERG1a/1b channels and <t>ICA‐105574</t> at +20 mV (nearly threefold); n = 5 for hERG1a; n = 8 for hERG1a/1b channels. *P < 0.05, significantly different from hERG1a channels.
Ica‐105574, supplied by Millipore, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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hERG1a/1b channels are less sensitive to ITP‐2. (A) Family of current traces showing reduced sensitivity of hERG1a/1b channels to ITP‐2. Currents were elicited as in Figure 1A. (B, C) Corresponding current–voltage relationships for hERG1a/1b steady‐state currents and tail currents before and after 3 μM ITP‐2. ITP‐2 selectively increases test pulse currents, similar to hERG1a channels. Data shown are means±SEM; n = 5. *P < 0.05; significantly different from control; two‐way ANOVA. (D, E) Bar graphs showing reduced sensitivity of hERG1a/1b channels to ITP‐2 (nearly sixfold); n = 13 for hERG1a; n = 8 for hERG1a/1b channels and <t>ICA‐105574</t> at +20 mV (nearly threefold); n = 5 for hERG1a; n = 8 for hERG1a/1b channels. *P < 0.05, significantly different from hERG1a channels.
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ica-105574  (Kanto Chemical)
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hERG1a/1b channels are less sensitive to ITP‐2. (A) Family of current traces showing reduced sensitivity of hERG1a/1b channels to ITP‐2. Currents were elicited as in Figure 1A. (B, C) Corresponding current–voltage relationships for hERG1a/1b steady‐state currents and tail currents before and after 3 μM ITP‐2. ITP‐2 selectively increases test pulse currents, similar to hERG1a channels. Data shown are means±SEM; n = 5. *P < 0.05; significantly different from control; two‐way ANOVA. (D, E) Bar graphs showing reduced sensitivity of hERG1a/1b channels to ITP‐2 (nearly sixfold); n = 13 for hERG1a; n = 8 for hERG1a/1b channels and <t>ICA‐105574</t> at +20 mV (nearly threefold); n = 5 for hERG1a; n = 8 for hERG1a/1b channels. *P < 0.05, significantly different from hERG1a channels.
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ica-105574  (Mitsubishi Tanabe)
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hERG1a/1b channels are less sensitive to ITP‐2. (A) Family of current traces showing reduced sensitivity of hERG1a/1b channels to ITP‐2. Currents were elicited as in Figure 1A. (B, C) Corresponding current–voltage relationships for hERG1a/1b steady‐state currents and tail currents before and after 3 μM ITP‐2. ITP‐2 selectively increases test pulse currents, similar to hERG1a channels. Data shown are means±SEM; n = 5. *P < 0.05; significantly different from control; two‐way ANOVA. (D, E) Bar graphs showing reduced sensitivity of hERG1a/1b channels to ITP‐2 (nearly sixfold); n = 13 for hERG1a; n = 8 for hERG1a/1b channels and <t>ICA‐105574</t> at +20 mV (nearly threefold); n = 5 for hERG1a; n = 8 for hERG1a/1b channels. *P < 0.05, significantly different from hERG1a channels.
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ica-105574  (Gaussian inc)
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hERG1a/1b channels are less sensitive to ITP‐2. (A) Family of current traces showing reduced sensitivity of hERG1a/1b channels to ITP‐2. Currents were elicited as in Figure 1A. (B, C) Corresponding current–voltage relationships for hERG1a/1b steady‐state currents and tail currents before and after 3 μM ITP‐2. ITP‐2 selectively increases test pulse currents, similar to hERG1a channels. Data shown are means±SEM; n = 5. *P < 0.05; significantly different from control; two‐way ANOVA. (D, E) Bar graphs showing reduced sensitivity of hERG1a/1b channels to ITP‐2 (nearly sixfold); n = 13 for hERG1a; n = 8 for hERG1a/1b channels and <t>ICA‐105574</t> at +20 mV (nearly threefold); n = 5 for hERG1a; n = 8 for hERG1a/1b channels. *P < 0.05, significantly different from hERG1a channels.
Ica 105574, supplied by Gaussian inc, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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hERG1a/1b channels are less sensitive to ITP‐2. (A) Family of current traces showing reduced sensitivity of hERG1a/1b channels to ITP‐2. Currents were elicited as in Figure 1A. (B, C) Corresponding current–voltage relationships for hERG1a/1b steady‐state currents and tail currents before and after 3 μM ITP‐2. ITP‐2 selectively increases test pulse currents, similar to hERG1a channels. Data shown are means±SEM; n = 5. *P < 0.05; significantly different from control; two‐way ANOVA. (D, E) Bar graphs showing reduced sensitivity of hERG1a/1b channels to ITP‐2 (nearly sixfold); n = 13 for hERG1a; n = 8 for hERG1a/1b channels and ICA‐105574 at +20 mV (nearly threefold); n = 5 for hERG1a; n = 8 for hERG1a/1b channels. *P < 0.05, significantly different from hERG1a channels.

Journal: British Journal of Pharmacology

Article Title: Modulation of K v 11.1 (hERG) channels by 5‐(((1H–indazol‐5‐yl)oxy)methyl)‐N‐(4‐(trifluoromethoxy)phenyl)pyrimidin‐2‐amine (ITP‐2), a novel small molecule activator

doi: 10.1111/bph.13859

Figure Lengend Snippet: hERG1a/1b channels are less sensitive to ITP‐2. (A) Family of current traces showing reduced sensitivity of hERG1a/1b channels to ITP‐2. Currents were elicited as in Figure 1A. (B, C) Corresponding current–voltage relationships for hERG1a/1b steady‐state currents and tail currents before and after 3 μM ITP‐2. ITP‐2 selectively increases test pulse currents, similar to hERG1a channels. Data shown are means±SEM; n = 5. *P < 0.05; significantly different from control; two‐way ANOVA. (D, E) Bar graphs showing reduced sensitivity of hERG1a/1b channels to ITP‐2 (nearly sixfold); n = 13 for hERG1a; n = 8 for hERG1a/1b channels and ICA‐105574 at +20 mV (nearly threefold); n = 5 for hERG1a; n = 8 for hERG1a/1b channels. *P < 0.05, significantly different from hERG1a channels.

Article Snippet: ICA‐105574 was purchased from Sigma (Bangalore, India).

Techniques:

ITP‐2 activates a trafficking‐deficient LQT2 mutant channel. (A, B) ITP‐2 and ICA‐105574 activated the LQT2 mutant G601S channel but with reduced potency. (C) ITP‐2 failed to activate the N470D LQT2 mutant channel, while ICA‐105574 could activate but again with reduced potency. (D) Bar graph showing comparison of ITP‐2 effects on wild type hERG (n = 13) and LQT2 mutant channels (n = 4) with those of ICA‐105574 (wild type, n = 5; mutantchannels, n = 4). Experiments were carried out at +20 mV.

Journal: British Journal of Pharmacology

Article Title: Modulation of K v 11.1 (hERG) channels by 5‐(((1H–indazol‐5‐yl)oxy)methyl)‐N‐(4‐(trifluoromethoxy)phenyl)pyrimidin‐2‐amine (ITP‐2), a novel small molecule activator

doi: 10.1111/bph.13859

Figure Lengend Snippet: ITP‐2 activates a trafficking‐deficient LQT2 mutant channel. (A, B) ITP‐2 and ICA‐105574 activated the LQT2 mutant G601S channel but with reduced potency. (C) ITP‐2 failed to activate the N470D LQT2 mutant channel, while ICA‐105574 could activate but again with reduced potency. (D) Bar graph showing comparison of ITP‐2 effects on wild type hERG (n = 13) and LQT2 mutant channels (n = 4) with those of ICA‐105574 (wild type, n = 5; mutantchannels, n = 4). Experiments were carried out at +20 mV.

Article Snippet: ICA‐105574 was purchased from Sigma (Bangalore, India).

Techniques: Mutagenesis