PMID- 34101862
OWN - NLM
STAT- MEDLINE
DCOM- 20220125
LR  - 20220125
IS  - 1099-0801 (Electronic)
IS  - 0269-3879 (Linking)
VI  - 35
IP  - 11
DP  - 2021 Nov
TI  - Comparative metabolomics and lipidomics study to evaluate the metabolic 
      differences between first- and second-generation mammalian or mechanistic target 
      of rapamycin inhibitors.
PG  - e5190
LID - 10.1002/bmc.5190 [doi]
AB  - Mammalian or mechanistic target of rapamycin (mTOR) drives its fundamental 
      cellular functions through two distinct catalytic subunits, mTORC1 and mTORC2, 
      and is frequently dysregulated in most cancers. To treat cancers, developed mTOR 
      inhibitors have been classified into first and second generations based on their 
      ability to inhibit single (first-generation) and dual (second-generation) mTOR 
      subunits. However, the underlying metabolic differences due to the effects of 
      first- and second-generation mTOR inhibitors have not been clearly evaluated. In 
      this study, rapamycin (sirolimus) and AZD8055 and PP242 were selected as first- 
      and second-generation mTOR inhibitors, respectively, to evaluate the metabolic 
      differences due to these two generations of mTOR inhibitors after a single oral 
      dose using untargeted metabolomics and lipidomics approaches. The metabolic 
      differences at each time point were compared using multivariate analysis. The 
      multivariate and data analyses showed that metabolic disparity was more prominent 
      within 8 h after drug administration and a broad class of metabolites were 
      affected by the administration of both generations of mTOR inhibitors. Among the 
      metabolite classes, changes in the pattern of fatty acids and 
      glycerophospholipids were opposite, specifically at 4 and 8 h between the two 
      generations of mTOR inhibitors. We speculate that the inhibition of the mTORC2 
      subunit by the second-generation mTOR inhibitor may have resulted in a distinct 
      metabolic pattern between the first- and second-generation inhibitors. Finally, 
      the findings of this study could assist in a more detailed understanding of the 
      key metabolic differences caused by first- and second-generation mTOR inhibitors.
CI  - (c) 2021 John Wiley & Sons, Ltd.
FAU - Rashid, Md Mamunur
AU  - Rashid MM
AD  - Molecular Recognition Research Center, Korea Institute of Science and Technology, 
      Seoul, South Korea.
AD  - Division of Bio-Medical Science and Technology, KIST School, Korea University of 
      Science and Technology (UST), Seoul, South Korea.
FAU - Lee, Hyunbeom
AU  - Lee H
AD  - Molecular Recognition Research Center, Korea Institute of Science and Technology, 
      Seoul, South Korea.
FAU - Park, Jinyoung
AU  - Park J
AD  - Molecular Recognition Research Center, Korea Institute of Science and Technology, 
      Seoul, South Korea.
FAU - Jung, Byung Hwa
AU  - Jung BH
AUID- ORCID: 0000-0002-7504-7132
AD  - Molecular Recognition Research Center, Korea Institute of Science and Technology, 
      Seoul, South Korea.
AD  - Division of Bio-Medical Science and Technology, KIST School, Korea University of 
      Science and Technology (UST), Seoul, South Korea.
LA  - eng
GR  - 2E30480/Korea Institute of Science and Technology/
GR  - HI18C1860/Ministry of Health & Welfare, Republic of Korea/
GR  - NRF2013M3A9C4078145/Ministry of Science, ICT and Future Planning/
PT  - Journal Article
DEP - 20210623
PL  - England
TA  - Biomed Chromatogr
JT  - Biomedical chromatography : BMC
JID - 8610241
RN  - 0 (Biomarkers)
RN  - 0 (MTOR Inhibitors)
SB  - IM
MH  - Animals
MH  - Biomarkers/blood/urine
MH  - Chromatography, High Pressure Liquid
MH  - Lipidomics/*methods
MH  - MTOR Inhibitors/*pharmacology
MH  - Male
MH  - Mass Spectrometry
MH  - Metabolome/*drug effects
MH  - Metabolomics/*methods
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - UHPLC-Orbitrap-MS
OT  - lipidomics
OT  - mTOR inhibitor
OT  - mammalian or mechanistic target of rapamycin, metabolomics
EDAT- 2021/06/09 06:00
MHDA- 2022/01/27 06:00
CRDT- 2021/06/08 17:38
PHST- 2021/05/30 00:00 [revised]
PHST- 2021/03/11 00:00 [received]
PHST- 2021/06/04 00:00 [accepted]
PHST- 2021/06/09 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/06/08 17:38 [entrez]
AID - 10.1002/bmc.5190 [doi]
PST - ppublish
SO  - Biomed Chromatogr. 2021 Nov;35(11):e5190. doi: 10.1002/bmc.5190. Epub 2021 Jun 
      23.