Table 1.
Clinical perspectives on the regulation of inflammation resolution.
| Group | Expected Beneficial Effect | Members | Prospects for Use in Atherosclerosis. Data on the Results of Research (ClinicalTrials.Gov Identifier) | Reference |
|---|---|---|---|---|
| PUFAs | Precursors for the biosynthesis of SPMs; other beneficial effects. |
ω-3 PUFAs | Numerous clinical trials have been conducted (NCT01310270, NCT00764010, NCT01367145, etc.). Additional research is required. |
[68,311,312] |
| Medications involved in the biosynthesis of SPMs | Production of aspirin-triggered SPMs; other beneficial clinical effects (antiplatelet activity; hypolipidemic effect; improvement of insulin resistance) |
- Aspirin - Statins - Pioglitazone |
Aspirin and statins have proven efficacy in treating patients with atherosclerosis. Additional research is required. | [95,268,269,272,274,313] |
| Synthetic analogues of SPMs | Anti-inflammatory effects; Pro-resolving actions; |
Lipoxin analogues (4 generation) |
It is the subject of studies on efficacy and safety. Many issues about pharmacodynamics and pharmacokinetics are unresolved. | [276,277,278] [285,286] |
| Anti-inflammatory effect; attenuation of neutrophil infiltration and stimulation of phagocytosis; attenuation of VSMC migration and neointimal hyperplasia | Resolvin analogues | It is the subject of studies on efficacy and safety. Many issues about pharmacodynamics and pharmacokinetics are unresolved. | ||
| Synthetic FPR2 agonists | Anti-inflammatory effects; pro-resolving action; cardioprotective properties |
Compound 43 (Cmpd43) Compound 17B |
Cmpd43 and Cmpd17b have shown positive effects in preclinical trials. | [189,291,292,314,315,316] |
| BMS-986235/ LAR-1219 |
BMS-986235 demonstrated positive effects in preclinical trials. BMS-986235 is in phase I clinical trials (NCT03335553) | |||
| ACT-389949 | ACT-389949 is in phase I clinical trials (NCT02099071, NCT02099201). No data on studies to evaluate efficacy in atherosclerosis. Additional research is required. |
|||
| 5-LOX inhibitors | Reduces the production of leukotriene | VIA-2291/ Atreleuton/ Abbott-85761 |
Atreleuton had been in phase II clinical trials for the treatment of acute coronary syndrome and atherosclerosis (NCT00352417, NCT00358826, NCT00552188). The research was discontinued |
[297,298,299,300,301,317,318] |
| Zileuton | Studied in patients with asthma and COPD; there are studies in coronary heart disease. | |||
| Setileuton/ MK 0633 |
Setileuton has been in phase II clinical trials for the treatment of atherosclerosis (NCT00421278). Further clinical trial discontinued | |||
| FLAP inhibitors | Inhibition of leukotriene biosynthesis | AZD5718/ Atuliflapon |
Phase II clinical trial in patients with acute coronary syndrome (NCT04601467) | [302,305,308,319,320,321,322,323,324,325] |
| Induces a switch in the formation of pro-inflammatory 5-LOX derivative LT towards inflammation-resolving 12/15-LOX derivative SPMs | BRP-201 | No data on studies to evaluate efficacy in atherosclerosis | ||
| Inhibited LT biosynthesis; inhibited microsomal prostaglandin E2 synthase-1 | BRP-187 | No data on studies to evaluate efficacy in atherosclerosis | ||
| Inhibition of leukotriene biosynthesis | BAY X 1005/ veliflapon | Studied in patients with acute coronary syndrome (Phase 3, NCT00353067). Participant enrollment has been suspended. |