GR-2397: Review of the Novel Siderophore-like Antifungal Agent for the Treatment of Invasive Aspergillosis
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 int...
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
|
| Series: | Journal of Fungi |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2309-608X/8/9/909 |
| _version_ | 1797486255868477440 |
|---|---|
| author | Karen Joy Shaw |
| author_facet | Karen Joy Shaw |
| author_sort | Karen Joy Shaw |
| collection | DOAJ |
| description | 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 <i>Aspergillus</i> spp. including azole-resistant strains, <i>Fusarium solani</i>, and <i>Candida glabrata</i> 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. |
| first_indexed | 2024-03-09T23:31:35Z |
| format | Article |
| id | doaj.art-d8c2af738cb446de9c455ac743b65131 |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T23:31:35Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-d8c2af738cb446de9c455ac743b651312023-11-23T17:09:05ZengMDPI AGJournal of Fungi2309-608X2022-08-018990910.3390/jof8090909GR-2397: Review of the Novel Siderophore-like Antifungal Agent for the Treatment of Invasive AspergillosisKaren Joy Shaw0Hearts Consulting Group, LLC, Poway, CA 92064, USAGR-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 <i>Aspergillus</i> spp. including azole-resistant strains, <i>Fusarium solani</i>, and <i>Candida glabrata</i> 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.https://www.mdpi.com/2309-608X/8/9/909GR-2397VL-2397ASP2397Sit1siderophoreferrichrome |
| spellingShingle | Karen Joy Shaw GR-2397: Review of the Novel Siderophore-like Antifungal Agent for the Treatment of Invasive Aspergillosis Journal of Fungi GR-2397 VL-2397 ASP2397 Sit1 siderophore ferrichrome |
| title | GR-2397: Review of the Novel Siderophore-like Antifungal Agent for the Treatment of Invasive Aspergillosis |
| title_full | GR-2397: Review of the Novel Siderophore-like Antifungal Agent for the Treatment of Invasive Aspergillosis |
| title_fullStr | GR-2397: Review of the Novel Siderophore-like Antifungal Agent for the Treatment of Invasive Aspergillosis |
| title_full_unstemmed | GR-2397: Review of the Novel Siderophore-like Antifungal Agent for the Treatment of Invasive Aspergillosis |
| title_short | GR-2397: Review of the Novel Siderophore-like Antifungal Agent for the Treatment of Invasive Aspergillosis |
| title_sort | gr 2397 review of the novel siderophore like antifungal agent for the treatment of invasive aspergillosis |
| topic | GR-2397 VL-2397 ASP2397 Sit1 siderophore ferrichrome |
| url | https://www.mdpi.com/2309-608X/8/9/909 |
| work_keys_str_mv | AT karenjoyshaw gr2397reviewofthenovelsiderophorelikeantifungalagentforthetreatmentofinvasiveaspergillosis |