Fosigotifator

Fosigotifator
Clinical data
Other namesABBV-CLS-7262; Fosigotifator sodium tromethamine
Legal status
Legal status
  • Investigational
Identifiers
  • [(2S)-1,4-Bis[[2-(4-chloro-3-fluorophenoxy)acetyl]amino]-2-bicyclo[2.2.2]octanyl]oxymethyl dihydrogen phosphate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC25H27Cl2F2N2O9P
Molar mass639.37 g·mol−1
3D model (JSmol)
  • C1CC2(CCC1(C[C@@H]2OCOP(=O)(O)O)NC(=O)COC3=CC(=C(C=C3)Cl)F)NC(=O)COC4=CC(=C(C=C4)Cl)F
  • InChI=1S/C25H27Cl2F2N2O9P/c26-17-3-1-15(9-19(17)28)37-12-22(32)30-24-5-7-25(8-6-24,21(11-24)39-14-40-41(34,35)36)31-23(33)13-38-16-2-4-18(27)20(29)10-16/h1-4,9-10,21H,5-8,11-14H2,(H,30,32)(H,31,33)(H2,34,35,36)/t21-,24?,25?/m0/s1
  • Key:IURMHIZNAHLQRX-ANYOXOOPSA-N

Fosigotifator is an experimental small-molecule related to ISRIB that activates the eukaryotic initiation factor eIF2; it was licensed by Calico from University of California, San Francisco and partnered with AbbVie.[1][2][3] Abbvie and Calico ran clinical trials to determine if the drug can treat amyotrophic lateral sclerosis (ALS)[4][5][6] and major depressive disorder.[1] A formulation of fosigotifator, as its monosodium phosphate salt mixed with tromethamine, is known as ABBV-CLS-7262. Fosigotifator has been patented by AbbVie and Calico as a prodrug for modulation of the integrated stress response pathway.[7]

In January 2025 Abbvie and Calico announced that the drug had failed a Phase 2/3 trial in ALS; in November 2025 Abbvie ended its partnership with Calico.[1]

References

  1. ^ a b c "Fosigotifator". alzforum.org. 21 Nov 2025. Retrieved 24 November 2025.
  2. ^ Masson, Gabrielle (13 November 2025). "AbbVie to end Calico collab, lays off researchers: Stat". www.fiercebiotech.com. Retrieved 24 November 2025.
  3. ^ "Fosigotifator - AbbVie/Calico - AdisInsight". Adisinsight. Retrieved 24 November 2025.
  4. ^ Arnold, F. J.; Nguyen, A. D.; Bedlack, R. S.; Bennett, C. L.; La Spada, A. R. (1 August 2023). "Intercellular transmission of pathogenic proteins in ALS: Exploring the pathogenic wave". Neurobiology of Disease. 184 106218. doi:10.1016/j.nbd.2023.106218. ISSN 0969-9961. PMID 37394036. S2CID 259300396.
  5. ^ Martinez-Gonzalez, Loreto; Martinez, Ana (1 February 2023). "Emerging clinical investigational drugs for the treatment of amyotrophic lateral sclerosis". Expert Opinion on Investigational Drugs. 32 (2): 141–160. doi:10.1080/13543784.2023.2178416. hdl:10261/308825. ISSN 1354-3784. PMID 36762798. S2CID 256738008.
  6. ^ Cho, William; Jeong, Anna; Malik, Paul; Boiser, Joey; Huang, Xiu; Rosebraugh, Matthew (25 April 2023). "A Phase 1 First-in-human Study to Investigate the Safety, Tolerability and Food Effect of ABBV-CLS-7262 (P6-4.002)". Neurology. 100 (17 Supplement 2): 4188. doi:10.1212/WNL.0000000000203810. ISSN 0028-3878. S2CID 258416815.
  7. ^ WO 2020077217, "Prodrug Modulators of the Integrated Stress Pathway", published 2020-04-16 


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