ChanTest pioneered development of the hERG
assay as a preclinical predictor of impaired repolarization due to non-cardiac drugs.
consists of 16 exons and spans 55 kb of genomic Sequence. The predicted topology of HERG
is shown in Figure 2 and is similar to KVLQT1.
PECO GLGU HERG
BLKI TBMU PIGU CRAU PAAU HOPU & COMU & LEAU 1 0.15 0.1 - 0.5 1.0 0.3 - + + 2 0.05 0.1 + 0.25 2.5 0.1 - + + 3 - - - 0.1 - + - + 0.1 4 0.2 + + 0.5 0.2 0.2 - + 0.5 5 1.5 + + 8.0 12.0 0.1 50.0 + 3.0 6 0.04 + + 0.15 0.45 0.07 - + 0.8 7 0.1 + + 0.11 - 0.11 - + 0.15 8 0.003 0.011 ?
To test that theory, they first demonstrated that HERG
lies within the expected region of chromosome 7.
In addition, other studies have also shown that it could inhibit the human ether-a-gogo-related gene (hERG
) potassium channel, prolong myocardial APD, and improve tachyarrhythmia in a concentration-dependent manner .
A561P KCNH2 mutation caused a trafficking defect of the HERG
This effect was evaluated by the probability of producing a positive Ames Test outcome (Ames test against Salmonella typhimurium TA97a, TA98, TA100, TA102, TA104, TA1535, TA1537 and TA1538), a positive endocrine disruptor test outcome, hERG
inhibition and irritant effects.
For instance cyclovirobuxine-D and dauricine inhibit HERG
[K.sup.+] channel, preferentially when the channel is found on its open state (Zhao et al.
Inside medicinal and synthetic chemistry themselves, I'd suggest thinking of better ways to do the things we already know are valuable: fluorination for making things more metabolically stable, to pick one, alternatives to basic tertiary amines when you run into hERG
channel and potential cardiovascular problems, good general ways to make compounds more soluble and easier to formulate (and good reactions to accomplish these things).
Vigneault ve arkadaslarinin calismasinda paliperidonun; kardiyak potasyum (K+) kanallari ile iliskili bir proteini kodlayan human ether-a-go-gorelated gene (HERG
) blokaji ile QT uzamasi meydana getirdigi ve potansiyel olarak kardiyak acidan guvensiz oldugu bildirilmistir (7).
Korolkova et al., "Probing the outer mouth structure of the hERG
channel with peptide toxin footprinting and molecular modeling," Biophysical Journal, vol.
Development of binary classification models for prediction of hERG
potassium channel blockage," Molecular Pharmaceutics, vol.