PMID- 28629736
OWN - NLM
STAT- MEDLINE
DCOM- 20180405
LR  - 20181202
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 810
DP  - 2017 Sep 5
TI  - KFP-H008 blocks gastric acid secretion through inhibiting H(+)-K(+)-ATPase.
PG  - 112-119
LID - S0014-2999(17)30428-4 [pii]
LID - 10.1016/j.ejphar.2017.06.020 [doi]
AB  - 1-(5-(1H-indol-5-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine 
      (KFP-H008)，a novel and potent potassium-competitive acid blocker for the 
      treatment of acid secretion related diseases, has not been reported previously. 
      In this study, we demonstrated that KFP-H008 inhibits basal acid secretion, 
      2-deoxy-D-glucose- (2DG-) stimulated gastric acid secretion in rats. KFP-H008 
      blocked histamine-stimulated acid secretion in rats and heidenhain pouch dogs and 
      reversed acid output in isolated gastric perfusion under histamine stimulation. 
      In all the animal experiments, KFP-H008 exerted a more effective, potent and 
      longer-lasting inhibitory action in comparison with lansoprazole, a proton pump 
      inhibitor (PPI) commonly used in clinic. KFP-H008 inhibited H(+)-K(+)-ATPase 
      activity both at pH 6.5 and pH 7.5, and was unaffected by pH. The inhibitory 
      action was reversible and was achieved in a K(+)-competitive manner. Furthermore, 
      KFP-H008 did not affect Na(+)-K(+)-ATPase activity, thus exhibiting high 
      selectivity, which is different from PPIs. In all, KFP-H008, a novel 
      potassium-competitive acid blocker, may provide new option for the patients with 
      acid-related diseases and provide longer-lasting inhibitory action than drugs 
      commonly used in clinical treatment.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Li, Cheng-Yuan
AU  - Li CY
AD  - State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical 
      Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
FAU - Su, Mei
AU  - Su M
AD  - State Key Laboratory of Natural Medicines, School of Pharmacy, China 
      Pharmaceutical University, Nanjing 210009, PR China.
FAU - Yan, Yun-Yi
AU  - Yan YY
AD  - State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical 
      Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
FAU - Zhou, Lin
AU  - Zhou L
AD  - State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical 
      Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
FAU - Ao, Lu-Yao
AU  - Ao LY
AD  - State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical 
      Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
FAU - Fang, Wei-Rong
AU  - Fang WR
AD  - State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical 
      Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. Electronic 
      address: weirongfang@163.com.
FAU - Li, Yun-Man
AU  - Li YM
AD  - State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical 
      Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. Electronic 
      address: yunmanlicpu@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20170616
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 
      (1-(5-(1H-indol-5-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine)
RN  - 0 (Indoles)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (Pyrroles)
RN  - 820484N8I3 (Histamine)
RN  - EC 3.6.3.10 (H(+)-K(+)-Exchanging ATPase)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Animals
MH  - Gastric Acid/*metabolism
MH  - H(+)-K(+)-Exchanging ATPase/*metabolism
MH  - Histamine/pharmacology
MH  - Indoles/*pharmacology
MH  - Male
MH  - Potassium/metabolism
MH  - Proton Pump Inhibitors/*pharmacology
MH  - Pyridines/*pharmacology
MH  - Pyrroles/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - Gastric acid secretion
OT  - H(+)-K(+)-ATPase
OT  - Potassium-competitive acid blocker
OT  - Proton pump inhibitor
EDAT- 2017/06/21 06:00
MHDA- 2018/04/06 06:00
CRDT- 2017/06/21 06:00
PHST- 2017/02/27 00:00 [received]
PHST- 2017/06/14 00:00 [revised]
PHST- 2017/06/15 00:00 [accepted]
PHST- 2017/06/21 06:00 [pubmed]
PHST- 2018/04/06 06:00 [medline]
PHST- 2017/06/21 06:00 [entrez]
AID - S0014-2999(17)30428-4 [pii]
AID - 10.1016/j.ejphar.2017.06.020 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2017 Sep 5;810:112-119. doi: 10.1016/j.ejphar.2017.06.020. Epub 
      2017 Jun 16.