PMID- 33255197
OWN - NLM
STAT- MEDLINE
DCOM- 20210409
LR  - 20210409
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 25
IP  - 23
DP  - 2020 Nov 24
TI  - Small Molecule Soluble Epoxide Hydrolase Inhibitors in Multitarget and 
      Combination Therapies for Inflammation and Cancer.
LID - 10.3390/molecules25235488 [doi]
LID - 5488
AB  - The enzyme soluble epoxide hydrolase (sEH) plays a central role in metabolism of 
      bioactive lipid signaling molecules. The substrate-specific hydrolase activity of 
      sEH converts epoxyeicosatrienoic acids (EETs) to less bioactive 
      dihydroxyeicosatrienoic acids. EETs exhibit anti-inflammatory, analgesic, 
      antihypertensive, cardio-protective and organ-protective properties. Accordingly, 
      sEH inhibition is a promising therapeutic strategy for addressing a variety of 
      diseases. In this review, we describe small molecule architectures that have been 
      commonly deployed as sEH inhibitors with respect to angiogenesis, inflammation 
      and cancer. We juxtapose commonly used synthetic scaffolds and natural products 
      within the paradigm of a multitarget approach for addressing inflammation and 
      inflammation induced carcinogenesis. Structural insights from the inhibitor 
      complexes and novel strategies for development of sEH-based multitarget 
      inhibitors are also presented. While sEH inhibition is likely to suppress 
      inflammation-induced carcinogenesis, it can also lead to enhanced angiogenesis 
      via increased EET concentrations. In this regard, sEH inhibitors in combination 
      chemotherapy are described. Urea and amide-based architectures feature 
      prominently across multitarget inhibition and combination chemotherapy 
      applications of sEH inhibitors.
FAU - Das Mahapatra, Amarjyoti
AU  - Das Mahapatra A
AUID- ORCID: 0000-0002-4411-6844
AD  - Department of Chemistry, Indian Institute of Technology Gandhinagar, Palaj, 
      Gandhinagar 382355, India.
FAU - Choubey, Rinku
AU  - Choubey R
AD  - Department of Chemistry, Indian Institute of Technology Gandhinagar, Palaj, 
      Gandhinagar 382355, India.
FAU - Datta, Bhaskar
AU  - Datta B
AD  - Department of Chemistry, Indian Institute of Technology Gandhinagar, Palaj, 
      Gandhinagar 382355, India.
AD  - Department of Biological Engineering, Indian Institute of Technology Gandhinagar, 
      Palaj, Gandhinagar 382355, India.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20201124
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Enzyme Inhibitors)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/chemistry/pharmacology/*therapeutic use
MH  - Antineoplastic Agents/chemistry/pharmacology/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use
MH  - Biomarkers
MH  - Catalysis
MH  - Cell Transformation, Neoplastic/drug effects/genetics/metabolism
MH  - Drug Therapy, Combination
MH  - Enzyme Inhibitors/chemistry/pharmacology/*therapeutic use
MH  - Epoxide Hydrolases/*antagonists & inhibitors/chemistry
MH  - Humans
MH  - Inflammation/complications/*drug therapy/etiology/metabolism
MH  - Molecular Targeted Therapy
MH  - Neoplasms/*drug therapy/etiology/metabolism
MH  - Neovascularization, Pathologic/drug therapy/metabolism
MH  - Solubility
PMC - PMC7727688
OTO - NOTNLM
OT  - combination chemotherapy
OT  - inflammation
OT  - multitarget therapy
OT  - soluble epoxide hydrolase (sEH) inhibitors
OT  - urea derivatives
COIS- The authors declare no conflict of interest.
EDAT- 2020/12/02 06:00
MHDA- 2021/04/10 06:00
PMCR- 2020/11/24
CRDT- 2020/12/01 01:08
PHST- 2020/10/28 00:00 [received]
PHST- 2020/11/13 00:00 [revised]
PHST- 2020/11/19 00:00 [accepted]
PHST- 2020/12/01 01:08 [entrez]
PHST- 2020/12/02 06:00 [pubmed]
PHST- 2021/04/10 06:00 [medline]
PHST- 2020/11/24 00:00 [pmc-release]
AID - molecules25235488 [pii]
AID - molecules-25-05488 [pii]
AID - 10.3390/molecules25235488 [doi]
PST - epublish
SO  - Molecules. 2020 Nov 24;25(23):5488. doi: 10.3390/molecules25235488.