Azeliragon

Summary

Azeliragon (CHEMBL3989929) is a phase-3 clinical-stage small molecule targeting AGER; indicated across 4 conditions including alzheimer disease and diabetic kidney disease.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (AGER)
• Indications: 4 conditions
• Clinical trials: 14
• Chemistry: 532.1 Da · C32H38ClN3O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3989929
Name	Azeliragon
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11180124
Molecular formula	C32H38ClN3O2
Molecular weight	532.1
InChIKey	KJNNWYBAOPXVJY-UHFFFAOYSA-N

SMILES: CCCCC1=NC(=CN1C2=CC=C(C=C2)OC3=CC=C(C=C3)Cl)C4=CC=C(C=C4)OCCCN(CC)CC

IUPAC name: 3-[4-[2-butyl-1-[4-(4-chlorophenoxy)phenyl]imidazol-4-yl]phenoxy]-N,N-diethylpropan-1-amine

Also known as: Azeliragon, PF-04494700, TTP-488, TTP448, TTP488, AZELIRAGON, azeliragon

Patent coverage: 132 distinct patent families (300 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
AGER	advanced glycosylation end-product specific receptor	Antagonist	6	0%	Q15109

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Advanced glycosylation end product-specific receptor.

Bioactivity

ChEMBL activities: 3 potent at pChembl ≥ 5 of 4 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
AGER	7.9	Kd	12.7	nM	CHEMBL_ACT_24917599
AGER	7.9	Kd	12.7	nM	CHEMBL_ACT_28862240
AGER	6.3	Kd	500	nM	CHEMBL_ACT_18138628

Target pathways

Aggregated over 1 target gene(s): AGER.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
TAK1-dependent IKK and NF-kappa-B activation	1	AGER
Advanced glycosylation endproduct receptor signaling	1	AGER
TRAF6 mediated NF-kB activation	1	AGER

Dominant GO biological processes

GO term	Targets
response to hypoxia	1
microglial cell activation	1
regulation of T cell mediated cytotoxicity	1
DNA replication	1
DNA repair	1
phagocytosis	1
inflammatory response	1
cell surface receptor signaling pathway	1
learning or memory	1
response to wounding	1
glucose mediated signaling pathway	1
neuron projection development	1
negative regulation of interleukin-10 production	1
positive regulation of chemokine production	1
positive regulation of interleukin-1 beta production	1

Indications & clinical

Indications

4 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
Alzheimer disease	3	MONDO:0004975	MONDO:0004975
diabetic kidney disease	2	MONDO:0005016	EFO:0000401
glioblastoma	2	MONDO:0018177	EFO:0000519
severe acute respiratory syndrome	2	MONDO:0005091	MONDO:0100096

Clinical trials

Total trials: 14.

Phase distribution

Phase	Trials
PHASE2	4
PHASE1/PHASE2	4
PHASE3	2
PHASE1	2
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05815485	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study to Determine the Safety and Effectiveness of Azeliragon in the Treatment of Patients Hospitalized for Coronavirus Disease 2019 (COVID-19) or Pneumonia
NCT02080364	PHASE3	TERMINATED	Evaluation of the Efficacy and Safety of Azeliragon (TTP488) in Patients With Mild Alzheimer’s Disease
NCT02916056	PHASE3	TERMINATED	2-Year Extension Study of Azeliragon in Subjects With Alzheimer’s Disease (STEADFAST Extension)
NCT05256745	PHASE1/PHASE2	RECRUITING	RAGE Inhibition to Decrease Cardiotoxicity in Women With Early Breast Cancer
NCT05766748	PHASE1/PHASE2	RECRUITING	Study of Effect of Azeliragon in Patients Refractory to Prior Treatment of Metastatic Pancreatic Cancer
NCT05789589	PHASE1/PHASE2	RECRUITING	Effect of Azeliragon Combined With Stereotactic Radiation Therapy in Patients With Brain Metastases
NCT05986851	PHASE2	ACTIVE_NOT_RECRUITING	Azeliragon in MGMT Unmethylated Glioblastoma
NCT00287183	PHASE2	COMPLETED	6-Month Safety And Efficacy Study Of TTP488 In Patients With Type 2 Diabetes And Persistent Albuminuria
NCT00566397	PHASE2	COMPLETED	A Phase 2 Study Evaluating The Efficacy And Safety Of PF 04494700 In Mild To Moderate Alzheimer’s Disease
NCT03980730	PHASE2	TERMINATED	Study of Azeliragon in Patients With Mild Alzheimer’s Disease and Impaired Glucose Tolerance
NCT05635734	PHASE1/PHASE2	COMPLETED	Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma
NCT06724926	PHASE1	ACTIVE_NOT_RECRUITING	Concurrent Azeliragon With Craniospinal Irradiation
NCT05773664	PHASE1	WITHDRAWN	Dexamethasone and Azeliragon for Management of Post-Resection Cerebral Edema in Patients with Glioblastoma
NCT06831526	EARLY_PHASE1	RECRUITING	Neoadjuvant Chemoradiotherapy With or Without Concurrent Azeliragon in Patients With Newly Diagnosed Glioblastoma

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

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

2 molecules share ≥1 primary target. Top 2 by shared-target count:

Molecule	Source	Status	Shared targets
Matrine	PubChem	Approved	AGER
Vilazodone	PubChem	Approved	AGER