Zatolmilast

Zatolmilast
Clinical data
Other names	BPN-14770
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name 2-[4-[[2-(3-chlorophenyl)-6-(trifluoromethyl)pyridin-4-yl]methyl]phenyl]acetic acid;
CAS Number	1606974-33-7;
PubChem CID	90111638;
IUPHAR/BPS	10451;
DrugBank	DB14790;
ChemSpider	75533972;
UNII	G786V328X6;
KEGG	D12173;
ChEMBL	ChEMBL4541964;
PDB ligand	KR7 (PDBe, RCSB PDB);
Chemical and physical data
Formula	C21H15ClF3NO2
Molar mass	405.80 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1=CC(=CC(=C1)Cl)C2=NC(=CC(=C2)CC3=CC=C(C=C3)CC(=O)O)C(F)(F)F;
	InChI InChI=1S/C21H15ClF3NO2/c22-17-3-1-2-16(12-17)18-9-15(10-19(26-18)21(23,24)25)8-13-4-6-14(7-5-13)11-20(27)28/h1-7,9-10,12H,8,11H2,(H,27,28); Key:LTSUMTMGJHPGFX-UHFFFAOYSA-N;

Zatolmilast is a investigational new drug that is being evaluated to treat fragile X syndrome.^[1] It is a PDE4D allosteric inhibitor.^[2]

It works by inhibiting breakdown of cyclic AMP (cAMP), with increased cAMP levels thought to increase neuronal connectivity. It has shown increased caregiver symptoms ratings and cognitive scores in a small clinical trial of 30 adults with fragile X syndrome.^[3]

References

↑ "Zatolmilast - Tetra Therapeutics". AdisInsight. Springer Nature Switzerland AG.
↑ Blauvelt A, Langley RG, Gordon KB, Silverberg JI, Eyerich K, Sommer MO, et al. (December 2023). "Next Generation PDE4 Inhibitors that Selectively Target PDE4B/D Subtypes: A Narrative Review". Dermatology and Therapy. 13 (12): 3031–3042. doi:10.1007/s13555-023-01054-3. PMC 10689637. PMID 37924462.
↑ Hagerman RJ, Hagerman PJ (17 July 2025). "The Spectrum of Fragile X Disorders". New England Journal of Medicine. 393 (3): 281–288. doi:10.1056/NEJMra2300487. PMID 40673587.

[1] "Zatolmilast - Tetra Therapeutics". AdisInsight. Springer Nature Switzerland AG.

[Blauvelt_2023-2] Blauvelt A, Langley RG, Gordon KB, Silverberg JI, Eyerich K, Sommer MO, et al. (December 2023). "Next Generation PDE4 Inhibitors that Selectively Target PDE4B/D Subtypes: A Narrative Review". Dermatology and Therapy. 13 (12): 3031–3042. doi:10.1007/s13555-023-01054-3. PMC 10689637. PMID 37924462.

[Hagerman_2025-3] Hagerman RJ, Hagerman PJ (17 July 2025). "The Spectrum of Fragile X Disorders". New England Journal of Medicine. 393 (3): 281–288. doi:10.1056/NEJMra2300487. PMID 40673587.

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