Table 1.
Lipid pathway modulators/therapeutics
| Compound | Target(s) | Mechanism of action | Clinical Indications (or disease model) | Status | Effect | References |
|---|---|---|---|---|---|---|
| Rupatadine | PAFR, H1 receptor | Dual affinity receptor competitive inhibitor | AR, CIU | In clinical use, Approved (E.U.) | Reduces rhinorrhea, sneezing, nasal and ocular pruritis and nasal congestion. Also >75 % reduction in hives in CIU pts at 4 weeks. | [17, 28] |
| Montelukast | CsytL1 | Competitive inhibitor of LTC4, LTD4 | Asthma, EIB, AR | In clinical use, approved | Improves FEV1, reduces exacerbations and blood eosinophil counts. | [29, 30, 31•] |
| Zileuton | 5-LO | Competitive inhibitor | Asthma, AERD | In clinical use, approved | Improves FEV1, reduced bronchodilator use and blood eosinophil counts. | [32] |
| OC000459 | DP2(CRTH2) | Competitive antagonist | Asthma, eosinophilic esophagitis (EoE) | Clinical trials underway | Reduced late airway response, reduced drop in FEV1, decreased eosinophil count after bronchial allergen challenge; Reduced esophageal eosinophil infiltration. | [33, 34] |
| Figolimod (FTY720) | S1P1, S1P3, S1P4, S1P5 | Pro-drug, functional S1P receptor antagonist | RRMS (asthma, AD, AR) | In clinical use, approved (MS only). (Pre-clinical) | In RRMS, reduced, relapse rate by ~50 %. (In asthma mouse models, IT-treatment suppressed AHR, inflammation. In mouse AD, topical-treatment reduced epidermal hypertrophy, MCs. In mouse model of AR, IN-treatment reduced inflammation, Th2 cytokines.) | [35, 36, 37•, 38] |
| SK1-1 (BML-258) | SphK1 | Competitive inhibitor | (Asthma) | (Preclinical) | (In asthma mouse models, IN-treatment suppressed AHR, inflammation, Th2 cytokine.) | [39] |
| AAL-R | S1P1, S1P3, S1P4, S1P5 | Functional S1P receptor antagonist | (Asthma) | (Preclinical) | (In asthma mouse models, IN-treatment suppressed AHR, inflammation, Th2 cytokine.) | [40] |
For preclinical testing, the murine disease model in which the compound was evaluated is bracketed in parentheses and italicized
5-LO 5-lipoxygenase, AD atopic dermatitis, AERD Aspirin-exacerbated respiratory disease, AHR airway hyper-responsiveness, AR allergic rhinitis, CIU chronic idiopathic urticarial, EIB exercise-induced bronchoconstriction, EU European Union, IT intratracheal, MC mast cells, RRMS relapsing remitting multiple sclerosis