Table 3.
Ligands targeting various enzymes relevant to pain
| Target/Category | Name | Mechanism | Preclinical | Clinical status | References |
|---|---|---|---|---|---|
| SPR |
(Quartet Medicine) Sulfasalazine SPRi3 |
SPE inhibitors, BH4 pathway | Analgesia – CFA, CCI, SNI | ND | 236 |
| FAAH and monogycerol lipase |
(Various) PF-04457845 BIA 10-2474 |
endocannabinoid pathway | Analgesia in several models | several clinical trials failed | 254, 295–298 |
| mPGE synthase 1 |
(Pfizer) PF 4693627 (Eli Lily) LY3023703 |
PGE pathway | Inflammatory pain | LY3023703 in phase 2 study of post-dental surgical pain | 239, 299–301, 302 |
| iNOS |
(Pfizer) Cindunistat |
iNOS inhibitor | Significant reduction on OA lesions in rodent and canine models | No clinical efficacy in patients with OA | 303 |
| Glutamate carboxypeptidase II | E2072 2-MPPA |
inhibitors | Neuropathy, neuropathic pain | ND | 304,305 |
| D-amino acid oxidase | SUN | inhibitor | Neuropathic pain, bone cancer pain | ND | 306 |
| Leukocyte elastase |
(Ono Pharma) Sivelestat |
inhibitor | Neuropathic pain | Approved for use during acute respiratory distress, no clinical trials yet for neuropathic pain | 248 |
| p38 |
(GSK) Losmapimod |
inhibitor | Inhibition of neuropathic pain | No differentiation from placebo | 251 |
Key: OA – Osteoarthritis; ND – no data on clinical development