Olodanrigan | Angiotensin II type 2 receptor antagonist

Olodanrigan (EMA401; CAS 1316755-16-4) is a potent (IC₅₀ = 39.5 nM) and selective (>10,000-fold selectivity AT₂R/AT₁R) antagonist of the angiotensin II type 2 receptor.¹ It produced dose-dependent relief of hindpaw sensitivity in a rat model of neuropathic pain¹ and showed efficacy in a human trial against postherpetic neuralgia².  Olodanrigan prevented paclitaxel-associated acute pain syndrome in mice.³ It blocked visceral hypersensitivity and colonic hyperpermeability in a rat model of irritable bowel syndrome.⁴ It was also able to inhibit proliferation of AT₂R-expressing glioblastoma spheroids and blocked their invasiveness and angiogenic capability.⁵

References/Citations:

1. Smith et al. (2013), Small Molecule Angiotensin II Type 2 Receptor (AT₂R) Antagonists as Novel Analgesics for Neuropathic Pain: Comparative Pharmacokinetics, Radioligand Binding, and Efficacy in Rats; Pain Med., 14 692
2. Rice et al. (2014), EMA401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: a randomized, double-blind, placebo-controlled phase 2 clinical trial; Lancet, 383 1637
3. Zanata et al. (2021), Blockade of bradykinin receptors or angiotensin II type 2 receptor prevents paclitaxel-associated acute pain syndrome in mice; Eur. J. Pain., 25 189
4. Nozu et al. (2021), EMA401, an angiotensin II type 2 receptor antagonist blocks visceral hypersensitivity and colonic hyperpermeability in rat model of irritable bowel syndrome; J. Pharmacol. Sci., 146 121
5. Perryman et al. (2022), Inhibition of the angiotensin II type 2 receptor AT2R is a novel therapeutic strategy for glioblastoma; Proc. Natl. Acad. Sci. USA, 119 e2116289119