Fosigotifator

Fosigotifator
Clinical data
Other names	ABBV-CLS-7262; Fosigotifator sodium tromethamine
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name [(2S)-1,4-Bis[[2-(4-chloro-3-fluorophenoxy)acetyl]amino]-2-bicyclo[2.2.2]octanyl]oxymethyl dihydrogen phosphate;
CAS Number	2415715-84-1 ; 2945073-88-9 (sodium tromethamine);
PubChem CID	153563259; 166177193;
DrugBank	DB19409;
ChemSpider	129309304;
UNII	3FQ7XKK8AY; BN9FN5629V;
KEGG	D13118; D13119;
ChEMBL	ChEMBL5315045;
Chemical and physical data
Formula	C25H27Cl2F2N2O9P
Molar mass	639.37 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES 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 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. Abbvie and Calico ran clinical trials to determine if the drug can treat amyotrophic lateral sclerosis (ALS) and major depressive disorder. 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.

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.

References

1 2 3 "Fosigotifator". alzforum.org. 21 Nov 2025. Retrieved 24 November 2025.
↑ Masson, Gabrielle (13 November 2025). "AbbVie to end Calico collab, lays off researchers: Stat". www.fiercebiotech.com. Retrieved 24 November 2025.
↑ "Fosigotifator - AbbVie/Calico - AdisInsight". Adisinsight. Retrieved 24 November 2025.
↑ 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.
↑ 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.
↑ 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.
↑ WO 2020077217, "Prodrug Modulators of the Integrated Stress Pathway", published 2020-04-16

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[AlzForum-1] 1 2 3 "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