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Lysophosphatidic acid type 2 receptor agonists in targeted drug development offer broad therapeutic potential
- Source :
- Journal of Lipid Research, Vol 60, Iss 3, Pp 464-474 (2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- The growth factor-like lipid mediator, lysophosphatidic acid (LPA), is a potent signaling molecule that influences numerous physiologic and pathologic processes. Manipulation of LPA signaling is of growing pharmacotherapeutic interest, especially because LPA resembles compounds with drug-like features. The action of LPA is mediated through activation of multiple types of molecular targets, including six G protein-coupled receptors that are clear targets for drug development. However, the LPA signaling has been linked to pathological responses that include promotion of fibrosis, atherogenesis, tumorigenesis, and metastasis. Thus, a question arises: Can we harness, in an LPA-like drug, the many beneficial activities of this lipid without eliciting its dreadful actions? We developed octadecyl thiophosphate (OTP; subsequently licensed as Rx100), an LPA mimic with higher stability in vivo than LPA. This article highlights progress made toward developing analogs like OTP and exploring prosurvival and regenerative LPA signaling. We determined that LPA prevents cell death triggered by various cellular stresses, including genotoxic stressors, and rescues cells condemned to apoptosis. LPA(2) agonists provide a new treatment option for secretory diarrhea and reduce gastric erosion caused by nonsteroidal anti-inflammatory drugs. The potential uses of LPA(2) agonists like OTP and sulfamoyl benzoic acid-based radioprotectins must be further explored for therapeutic uses.
- Subjects :
- autotaxin
0301 basic medicine
Programmed cell death
Rx100
QD415-436
030204 cardiovascular system & hematology
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
In vivo
Drug Discovery
Lysophosphatidic acid
Animals
Humans
Amino Acid Sequence
Receptors, Lysophosphatidic Acid
Receptor
gastric erosion
radiation mitigator
Chemistry
secretory diarrhea
apoptosis
Cell Biology
Lipid signaling
JLR Perspectives
030104 developmental biology
Drug development
Apoptosis
Cancer research
lipids (amino acids, peptides, and proteins)
biological phenomena, cell phenomena, and immunity
Autotaxin
DNA Damage
Signal Transduction
Subjects
Details
- ISSN :
- 00222275
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- Journal of Lipid Research
- Accession number :
- edsair.doi.dedup.....72817fc5aff2438ec2303f6b342fb0b4