Zatolmilast

Summary

Zatolmilast (CHEMBL4541964) is a phase-3 clinical-stage small molecule; indicated across 3 conditions including fragile x syndrome and alzheimer disease.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Indications: 3 conditions
• Clinical trials: 14
• Chemistry: 405.8 Da · C21H15ClF3NO2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4541964
Name	Zatolmilast
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	90111638
Molecular formula	C21H15ClF3NO2
Molecular weight	405.8
InChIKey	LTSUMTMGJHPGFX-UHFFFAOYSA-N

SMILES: C1=CC(=CC(=C1)Cl)C2=NC(=CC(=C2)CC3=CC=C(C=C3)CC(=O)O)C(F)(F)F

IUPAC name: 2-[4-[[2-(3-chlorophenyl)-6-(trifluoromethyl)-4-pyridinyl]methyl]phenyl]acetic acid

Also known as: BPN-14770, Bpn14770, BPN14770, Zatolmilast, ZATOLMILAST

Patent coverage: 56 distinct patent families (151 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 121 (80%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: 3’,5’-cyclic-AMP phosphodiesterase 4B, 3’,5’-cyclic-AMP phosphodiesterase 4D, Cytochrome P450 3A4, Cytochrome P450 2C19.

Bioactivity

ChEMBL activities: 6 potent at pChembl ≥ 5 of 8 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PDE4D	8.13	IC50	7.4	nM	CHEMBL_ACT_24984957
PDE4D	8.11	IC50	7.8	nM	CHEMBL_ACT_24776143
PDE4D	8.11	IC50	7.8	nM	CHEMBL_ACT_24984956
PDE4D	8.1	IC50	8	nM	CHEMBL_ACT_25710748
PDE4D	6.9	IC50	127	nM	CHEMBL_ACT_19231172
PDE4B	5.7	IC50	2013	nM	CHEMBL_ACT_19231006

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

3 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
fragile X syndrome	3	MONDO:0010383	MONDO:0010383
Alzheimer disease	2	MONDO:0004975	MONDO:0004975
cognitive disorder	1	MONDO:0002039	MONDO:0002039

Clinical trials

Total trials: 14.

Phase distribution

Phase	Trials
PHASE1	7
PHASE2	3
PHASE3	2
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05367960	PHASE3	ACTIVE_NOT_RECRUITING	An Open-Label Extension Study of BPN14770 in Subjects With Fragile X Syndrome
NCT05163808	PHASE2/PHASE3	COMPLETED	A Randomized Study of BPN14770 in Male Adolescents (Aged 9 to < 18 Years) With Fragile X Syndrome
NCT05358886	PHASE3	COMPLETED	A Study of BPN14770 in Male Adults (Aged 18 to 45) With Fragile X Syndrome
NCT06717438	PHASE2	ACTIVE_NOT_RECRUITING	Study of Zatolmilast (BPN14770) in Participants With PPP2R5D Neurodevelopmental Disorder (Jordan’s Syndrome [JS])
NCT03569631	PHASE2	COMPLETED	A 2-Period Crossover Study of BPN14770 in Adults Males With Fragile X Syndrome
NCT03817684	PHASE2	COMPLETED	Tetra PICASSO AD Trial: Study to Evaluate Effects of BPN14770 in Early Alzheimer’s Subjects
NCT03861000	PHASE1/PHASE2	COMPLETED	Title: Evaluation of a Novel PET Radioligand for Phosphodiesterase-4D (PDE4D)
NCT02648672	PHASE1	COMPLETED	BPN14770 Single Ascending Dose Study in Healthy Male and Female Subjects
NCT02840279	PHASE1	COMPLETED	A Multiple Ascending Dose Study of BPN14770 in Healthy Young and Elderly Male or Female Subjects
NCT03030105	PHASE1	COMPLETED	Study to Evaluate the Effects of BPN14770 on Scopolamine-induced Cognitive Impairment in Healthy Volunteers
NCT04044781	PHASE1	WITHDRAWN	A Phase 1, Open-Label, PET Study of T2310 & BPN14770
NCT07011992	PHASE1	COMPLETED	A Study to Assess the Effects of BPN14770 on Rosuvastatin
NCT07012005	PHASE1	COMPLETED	Study of BPN14770 in Participants With Severe Renal Impairment and Healthy Controls
NCT07018492	PHASE1	COMPLETED	Phase 1 Study of BPN14770 in Participants With Hepatic Impairment and Healthy Controls

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).