PMID- 31233785
OWN - NLM
STAT- MEDLINE
DCOM- 20200124
LR  - 20200124
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 60
DP  - 2019 Oct
TI  - A comprehensive evaluation of anti-diabetic drugs on nuclear receptor PXR 
      platform.
PG  - 347-358
LID - S0887-2333(18)30707-0 [pii]
LID - 10.1016/j.tiv.2019.06.015 [doi]
AB  - Pregnane & Xenobiotic Receptor (PXR), one of the members of nuclear receptor 
      superfamily, acts as a 'master-regulator' of drug metabolism and disposition 
      machinery (DMD). Activation of PXR enables detoxification and elimination of 
      toxic xenobiotics/endobiotics, and defends our body against chemical insults. On 
      the contrary, PXR activation also imposes a serious concern for drug-drug 
      interactions (DDIs). Such DDIs could either decrease the efficacy or lead to 
      accumulation of co-administered drugs at toxic level. Therefore, it is desirable 
      that during drug development process the small drug molecules are screened on 
      PXR-platform prior to their clinical trial and prevent late stage failures. In 
      view of this, we have selected a group of anti-diabetic drug molecules to examine 
      if the success and potential failure of small molecule modulators can be 
      pre-assessed and judiciously correlated on PXR platform. For this purpose, we 
      have examined the PXR activation potential of the selected anti-diabetic drugs. 
      Subsequent to screening of these anti-diabetic drugs, we elaborated the study 
      further with rosiglitazone and pioglitazone (thiazolidinediones, TZDs) which are 
      oral anti-diabetic formulations and have been in controversy owing to their 
      association with cardiotoxicity and bladder cancer respectively. Our study 
      revealed that some of the selected anti-diabetic drugs possess PXR activation 
      potential, implying that these can up-regulate the expression of CYP3A4, UGT1A1, 
      MDR1 and thereby can be predicted to inflict undesirable consequences.
CI  - Copyright (c) 2019. Published by Elsevier Ltd.
FAU - Singh, Shashi Kala
AU  - Singh SK
AD  - Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 
      110067, India.
FAU - Yende, Ashutosh S
AU  - Yende AS
AD  - Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 
      110067, India.
FAU - Ponnusamy, Kalaiarasan
AU  - Ponnusamy K
AD  - School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India.
FAU - Tyagi, Rakesh K
AU  - Tyagi RK
AD  - Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 
      110067, India. Electronic address: rktyagi@yahoo.com.
LA  - eng
PT  - Journal Article
DEP - 20190621
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Pregnane X Receptor)
RN  - 0 (RNA, Small Interfering)
RN  - 05V02F2KDG (Rosiglitazone)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - EC 2.4.1.- (UGT1A1 enzyme)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics
MH  - Animals
MH  - Cell Line
MH  - Chlorocebus aethiops
MH  - Cytochrome P-450 CYP3A/genetics/metabolism
MH  - Drug Interactions
MH  - Glucuronosyltransferase/genetics
MH  - Humans
MH  - Hypoglycemic Agents/*pharmacology
MH  - Pioglitazone/pharmacology
MH  - Pregnane X Receptor/genetics/*metabolism
MH  - RNA, Small Interfering/genetics
MH  - Rosiglitazone/pharmacology
OTO - NOTNLM
OT  - Anti-diabetic drugs
OT  - Drug screening
OT  - Promoter-reporter
OT  - Small molecules
OT  - Stable cell line
EDAT- 2019/06/25 06:00
MHDA- 2020/01/25 06:00
CRDT- 2019/06/25 06:00
PHST- 2018/11/09 00:00 [received]
PHST- 2019/06/09 00:00 [revised]
PHST- 2019/06/20 00:00 [accepted]
PHST- 2019/06/25 06:00 [pubmed]
PHST- 2020/01/25 06:00 [medline]
PHST- 2019/06/25 06:00 [entrez]
AID - S0887-2333(18)30707-0 [pii]
AID - 10.1016/j.tiv.2019.06.015 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2019 Oct;60:347-358. doi: 10.1016/j.tiv.2019.06.015. Epub 2019 
      Jun 21.