Tozadenant

Summary

Tozadenant (CHEMBL2105747) is a phase-3 clinical-stage small molecule targeting ADORA2A; indicated across 3 conditions including parkinson disease and liver disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (ADORA2A)
• Indications: 3 conditions
• Clinical trials: 7
• Chemistry: 406.5 Da · C19H26N4O4S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2105747
Name	Tozadenant
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11618368
Molecular formula	C19H26N4O4S
Molecular weight	406.5
InChIKey	XNBRWUQWSKXMPW-UHFFFAOYSA-N

SMILES: CC1(CCN(CC1)C(=O)NC2=NC3=C(C=CC(=C3S2)N4CCOCC4)OC)O

IUPAC name: 4-hydroxy-N-(4-methoxy-7-morpholin-4-yl-1,3-benzothiazol-2-yl)-4-methylpiperidine-1-carboxamide

Also known as: A-2A (3), A2A (3), A2A-(3), RO-4494351, RO-4494351000, RO4494351, SYN-115, SYN115, Tozadenant, TOZADENANT

Patent coverage: 257 distinct patent families (742 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 487 (66%) 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

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
ADORA2A	A2A receptor	Antagonist	8.3	0.4%	P29274

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Adenosine receptor A1, Adenosine receptor A2a, Adenosine receptor A2b, Adenosine receptor A3, Adenosine receptor A2a.

Bioactivity

ChEMBL activities: 21 potent at pChembl ≥ 5 of 21 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ADORA2A	9.52	Ki	0.3	nM	CHEMBL_ACT_18008898
ADORA2A	8.47	Ki	3.4	nM	CHEMBL_ACT_24772344
ADORA2A	8.41	Ki	3.9	nM	CHEMBL_ACT_22924930
ADORA2A	8.3	Ki	5	nM	CHEMBL_ACT_14645612
ADORA2A	8.3	Ki	5	nM	CHEMBL_ACT_22756961
ADORA2A	8.3	Ki	5	nM	CHEMBL_ACT_24772314
ADORA2A	8.08	Ki	8.3	nM	CHEMBL_ACT_22459717
ADORA2A	7.96	Ki	11	nM	CHEMBL_ACT_18008795
ADORA2A	7.96	Ki	11	nM	CHEMBL_ACT_24777228
P30543	7.73	Ki	18.7	nM	CHEMBL_ACT_22924939
ADORA2B	6.16	Ki	700	nM	CHEMBL_ACT_14644367
ADORA2B	6.16	Ki	700	nM	CHEMBL_ACT_22756956
ADORA1	5.87	Ki	1350	nM	CHEMBL_ACT_14645650
ADORA1	5.87	Ki	1350	nM	CHEMBL_ACT_22756959
ADORA3	5.8	Ki	1570	nM	CHEMBL_ACT_14645690
ADORA1	5.77	Ki	1700	nM	CHEMBL_ACT_18008961
ADORA1	5.77	Ki	1700	nM	CHEMBL_ACT_24777234
ADORA1	5.65	Ki	2240	nM	CHEMBL_ACT_22459654
ADORA1	5.47	Ki	3380	nM	CHEMBL_ACT_22924951
ADORA2B	5.3	Ki	5000	nM	CHEMBL_ACT_18008970
ADORA3	5.3	Ki	5000	nM	CHEMBL_ACT_18008976

Target pathways

Aggregated over 1 target gene(s): ADORA2A.

Top Reactome pathways

15 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	1	ADORA2A
Signaling by NTRKs	1	ADORA2A
Activation of TRKA receptors	1	ADORA2A
NGF-independant TRKA activation	1	ADORA2A
Signaling by NTRK1 (TRKA)	1	ADORA2A
Signaling by GPCR	1	ADORA2A
Class A/1 (Rhodopsin-like receptors)	1	ADORA2A
GPCR downstream signalling	1	ADORA2A
Metabolism of proteins	1	ADORA2A
Adenosine P1 receptors	1	ADORA2A
Nucleotide-like (purinergic) receptors	1	ADORA2A
G alpha (s) signalling events	1	ADORA2A
GPCR ligand binding	1	ADORA2A
Surfactant metabolism	1	ADORA2A
Signaling by Receptor Tyrosine Kinases	1	ADORA2A

Dominant GO biological processes

GO term	Targets
synaptic transmission, dopaminergic	1
G protein-coupled adenosine receptor signaling pathway	1
response to amphetamine	1
regulation of DNA-templated transcription	1
phagocytosis	1
apoptotic process	1
inflammatory response	1
cellular defense response	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
cell-cell signaling	1
synaptic transmission, cholinergic	1
central nervous system development	1
blood coagulation	1

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
Parkinson disease	3	MONDO:0005180	MONDO:0005180
liver disorder	1	MONDO:0005154	EFO:0001421
cocaine dependence	0	MONDO:0005186	EFO:0002610

Clinical trials

Total trials: 7.

Phase distribution

Phase	Trials
PHASE1	3
PHASE3	2
PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02453386	PHASE3	TERMINATED	Safety and Efficacy Study of Tozadenant to Treat End of Dose Wearing Off in Parkinson’s Patients
NCT03051607	PHASE3	TERMINATED	Safety and Tolerability of Tozadenant as Adjunctive Therapy in Levodopa-Treated Patients With Parkinson’s Disease.
NCT00605553	PHASE2	COMPLETED	Study to Evaluate SYN115 in Parkinson’s Disease
NCT02240290	PHASE1	COMPLETED	Study to Evaluate the Absorption, Distribution, Break Down and Elimination and the Safety of 14C-Labeled Tozadenant
NCT03200080	PHASE1	TERMINATED	A Study to Determine the Abuse Potential of Tozadenant Relative to D-Amphetamine and Placebo When Administered Orally in Healthy, Non-Dependent, Recreational Polydrug Users
NCT03212313	PHASE1	TERMINATED	Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Tozadenant
NCT00783276	EARLY_PHASE1	COMPLETED	An fMRI Study of SYN115 in Cocaine Dependent Subjects

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.

89 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
ADENOSINE	ChEMBL	Phase 4 (approved)	ADORA2A
ALLOPURINOL	ChEMBL	Phase 4 (approved)	ADORA2A
AMILORIDE	ChEMBL	Phase 4 (approved)	ADORA2A
AMPHETAMINE	ChEMBL	Phase 4 (approved)	ADORA2A
BALSALAZIDE	ChEMBL	Phase 4 (approved)	ADORA2A
BITHIONOL	ChEMBL	Phase 4 (approved)	ADORA2A
CAFFEINE	ChEMBL	Phase 4 (approved)	ADORA2A
CLOFARABINE	ChEMBL	Phase 4 (approved)	ADORA2A
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	ADORA2A
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	ADORA2A
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	ADORA2A
ECONAZOLE	ChEMBL	Phase 4 (approved)	ADORA2A
EPALRESTAT	ChEMBL	Phase 4 (approved)	ADORA2A
ERLOTINIB	ChEMBL	Phase 4 (approved)	ADORA2A
ETHINYL ESTRADIOL	ChEMBL	Phase 4 (approved)	ADORA2A
FEDRATINIB	ChEMBL	Phase 4 (approved)	ADORA2A
GENTIAN VIOLET	ChEMBL	Phase 4 (approved)	ADORA2A
GLAFENINE	ChEMBL	Phase 4 (approved)	ADORA2A
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	ADORA2A
IBRUTINIB	ChEMBL	Phase 4 (approved)	ADORA2A
IBUDILAST	ChEMBL	Phase 4 (approved)	ADORA2A
IMIQUIMOD	ChEMBL	Phase 4 (approved)	ADORA2A
ISTRADEFYLLINE	ChEMBL	Phase 4 (approved)	ADORA2A
MEFLOQUINE	ChEMBL	Phase 4 (approved)	ADORA2A
MICONAZOLE	ChEMBL	Phase 4 (approved)	ADORA2A
NEVIRAPINE	ChEMBL	Phase 4 (approved)	ADORA2A
NIFEDIPINE	ChEMBL	Phase 4 (approved)	ADORA2A
NIMESULIDE	ChEMBL	Phase 4 (approved)	ADORA2A
NINTEDANIB	ChEMBL	Phase 4 (approved)	ADORA2A
NISOLDIPINE	ChEMBL	Phase 4 (approved)	ADORA2A
NITAZOXANIDE	ChEMBL	Phase 4 (approved)	ADORA2A
OSIMERTINIB	ChEMBL	Phase 4 (approved)	ADORA2A
PENTOSTATIN	ChEMBL	Phase 4 (approved)	ADORA2A
PYRVINIUM	ChEMBL	Phase 4 (approved)	ADORA2A
RALOXIFENE	ChEMBL	Phase 4 (approved)	ADORA2A
REGADENOSON	ChEMBL	Phase 4 (approved)	ADORA2A
RIFAMPIN	ChEMBL	Phase 4 (approved)	ADORA2A
RIFAXIMIN	ChEMBL	Phase 4 (approved)	ADORA2A
SILDENAFIL	ChEMBL	Phase 4 (approved)	ADORA2A
SUNITINIB	ChEMBL	Phase 4 (approved)	ADORA2A
TAMOXIFEN	ChEMBL	Phase 4 (approved)	ADORA2A
THEOPHYLLINE	ChEMBL	Phase 4 (approved)	ADORA2A
THIOTHIXENE	ChEMBL	Phase 4 (approved)	ADORA2A
TRIOXSALEN	ChEMBL	Phase 4 (approved)	ADORA2A
APADENOSON	ChEMBL	Phase 3	ADORA2A
BINODENOSON	ChEMBL	Phase 3	ADORA2A
DEFACTINIB	ChEMBL	Phase 3	ADORA2A
DIACEREIN	ChEMBL	Phase 3	ADORA2A
NAMODENOSON	ChEMBL	Phase 3	ADORA2A
OTILONIUM BROMIDE	ChEMBL	Phase 3	ADORA2A
PRELADENANT	ChEMBL	Phase 3	ADORA2A
ROLOFYLLINE	ChEMBL	Phase 3	ADORA2A
TONAPOFYLLINE	ChEMBL	Phase 3	ADORA2A
TRABODENOSON	ChEMBL	Phase 3	ADORA2A
UMIFENOVIR	ChEMBL	Phase 3	ADORA2A
CEP-11981	ChEMBL	Phase 2	ADORA2A
CIFORADENANT	ChEMBL	Phase 2	ADORA2A
DENBUFYLLINE	ChEMBL	Phase 2	ADORA2A
DERENOFYLLINE	ChEMBL	Phase 2	ADORA2A
ENPROFYLLINE	ChEMBL	Phase 2	ADORA2A