GR-2397 (previously VL-2397, ASP2397) is a first-in-class antifungal agent for the treatment of invasive aspergillosis. This siderophore-like molecule resembles ferrichrome; however, it is differentiated by three amino acid changes and an aluminum rather than iron chelate. GR-2397 is transported into fungal cells via the Sit1 transporter, which is not found in humans, leading to fungal specificity. Although the precise mechanism of action is currently unknown, GR-2397 is active against Aspergillus spp. including azole-resistant strains, Fusarium solani, and Candida glabrata in addition to other organisms. Efficacy has been demonstrated in several animal models of invasive aspergillosis, including a 24 h delayed-treatment model where rapid fungicidal activity was observed. Phase 1 single- and multiple-ascending intravenous dose studies showed that GR-2397 was safe and well-tolerated in humans. No signs of GR-2397 accumulation were observed following IV infusions of 300, 600, and 1200 mg every 24 h (q24h) for 7 days. The favorable safety, tolerability and drug-drug interaction profile, along with good tissue distribution, support further development of GR-2397 as a new treatment option for patients with invasive aspergillosis. This systematic review summarizes the published findings of GR-2397.
Keywords: ASP2397; Aspergillus; GR-2397; Sit1; VL-2397; antifungal; ferrichrome; siderophore.