Preladenant

Summary

Preladenant (CHEMBL240624) is a phase-3 clinical-stage small molecule targeting ADORA1, ADORA2A, and ADORA2B; indicated across 3 conditions including parkinson disease and liver disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 4 (ADORA1, ADORA2A, ADORA2B…)
• Indications: 3 conditions
• Clinical trials: 10
• Chemistry: 503.6 Da · C25H29N9O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL240624
Name	Preladenant
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	10117987
Molecular formula	C25H29N9O3
Molecular weight	503.6
InChIKey	DTYWJKSSUANMHD-UHFFFAOYSA-N

SMILES: COCCOC1=CC=C(C=C1)N2CCN(CC2)CCN3C4=C(C=N3)C5=NC(=NN5C(=N4)N)C6=CC=CO6

IUPAC name: 4-(furan-2-yl)-10-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-1-yl]ethyl]-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-7-amine

Also known as: MK-3814, Preladenant, SCH 420814, Sch-420814, SCH-420814, preladenant, PRELADENANT

Parent form; salt/anhydrous children: CHEMBL540115

Patent coverage: 359 distinct patent families (1,077 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
ADORA1	A1 receptor	Antagonist	6	0.3%	P30542
ADORA2A	A2A receptor	Antagonist	9.05	0.4%	P29274
ADORA2B	A2B receptor	Antagonist	6	0.5%	P29275
ADORA3	A3 receptor	Antagonist	6	0%	P0DMS8

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: Adenosine receptor A1, Adenosine receptor A2a, Adenosine receptor A2a, Adenosine receptor A1.

Bioactivity

ChEMBL activities: 24 potent at pChembl ≥ 5 of 24 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ADORA2A	9.5	Kd	0.32	nM	CHEMBL_ACT_6284475
ADORA2A	9.3	Ki	0.5	nM	CHEMBL_ACT_18694862
ADORA2A	9.3	Ki	0.5	nM	CHEMBL_ACT_24710025
ADORA2A	9.3	Ki	0.5	nM	CHEMBL_ACT_24772320
ADORA2A	9.22	Ki	0.6	nM	CHEMBL_ACT_14645602
P30543	9.18	Ki	0.66	nM	CHEMBL_ACT_13299735
ADORA2A	9.06	Ki	0.88	nM	CHEMBL_ACT_24354310
ADORA2A	9.05	Ki	0.88	nM	CHEMBL_ACT_13299673
ADORA2A	9	Ki	1	nM	CHEMBL_ACT_13863092
ADORA2A	8.96	Ki	1.1	nM	CHEMBL_ACT_14645603
ADORA2A	8.96	Ki	1.1	nM	CHEMBL_ACT_19125754
ADORA2A	8.96	Ki	1.1	nM	CHEMBL_ACT_2019609
ADORA2A	8.96	Ki	1.1	nM	CHEMBL_ACT_22757018
ADORA2A	8.89	Ki	1.3	nM	CHEMBL_ACT_28831331
ADORA2A	8.8	Ki	1.58	nM	CHEMBL_ACT_6284467
P30543	8.6	Ki	2.5	nM	CHEMBL_ACT_2019634
P30543	8.6	IC50	2.5	nM	CHEMBL_ACT_28802834
ADORA2A	8.3	Ki	5	nM	CHEMBL_ACT_3424227
ADORA2A	8.3	Ki	5	nM	CHEMBL_ACT_5207186
P25099	7.16	Ki	68.7	nM	CHEMBL_ACT_13299765
ADORA1	6.53	Ki	295	nM	CHEMBL_ACT_13299704
ADORA1	6.53	Ki	295	nM	CHEMBL_ACT_24354294
ADORA1	6.47	Ki	337	nM	CHEMBL_ACT_28831328
ADORA1	5.83	Ki	1474	nM	CHEMBL_ACT_14645641

Target pathways

Aggregated over 4 target gene(s): ADORA1, ADORA2A, ADORA2B, ADORA3.

Top Reactome pathways

23 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	4	ADORA1, ADORA2A, ADORA2B, ADORA3
Signaling by GPCR	4	ADORA1, ADORA2A, ADORA2B, ADORA3
Class A/1 (Rhodopsin-like receptors)	4	ADORA1, ADORA2A, ADORA2B, ADORA3
GPCR downstream signalling	4	ADORA1, ADORA2A, ADORA2B, ADORA3
Adenosine P1 receptors	4	ADORA1, ADORA2A, ADORA2B, ADORA3
Nucleotide-like (purinergic) receptors	4	ADORA1, ADORA2A, ADORA2B, ADORA3
GPCR ligand binding	4	ADORA1, ADORA2A, ADORA2B, ADORA3
Metabolism of proteins	2	ADORA2A, ADORA2B
G alpha (s) signalling events	2	ADORA2A, ADORA2B
G alpha (i) signalling events	2	ADORA1, ADORA3
Surfactant metabolism	2	ADORA2A, ADORA2B
Disease	1	ADORA2B
Signaling by NTRKs	1	ADORA2A
Activation of TRKA receptors	1	ADORA2A
NGF-independant TRKA activation	1	ADORA2A
Signaling by NTRK1 (TRKA)	1	ADORA2A
Infectious disease	1	ADORA2B
Signaling by Receptor Tyrosine Kinases	1	ADORA2A
Leishmania infection	1	ADORA2B
ADORA2B mediated anti-inflammatory cytokines production	1	ADORA2B
Anti-inflammatory response favouring Leishmania parasite infection	1	ADORA2B
Leishmania parasite growth and survival	1	ADORA2B
Parasitic Infection Pathways	1	ADORA2B

Dominant GO biological processes

GO term	Targets
signal transduction	4
G protein-coupled receptor signaling pathway	4
G protein-coupled adenosine receptor signaling pathway	4
inflammatory response	3
negative regulation of cell population proliferation	3
vasodilation	3
presynaptic modulation of chemical synaptic transmission	3
phagocytosis	2
cell-cell signaling	2
response to purine-containing compound	2
excitatory postsynaptic potential	2
apoptotic signaling pathway	2
negative regulation of inflammatory response	2
adenylate cyclase-activating G protein-coupled receptor signaling pathway	2
regulation of norepinephrine secretion	2

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
neoplasm	1	MONDO:0005070	EFO:0000616

Clinical trials

Total trials: 10.

Phase distribution

Phase	Trials
PHASE2	5
PHASE1	3
PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01215227	PHASE3	TERMINATED	An Active-Controlled Extension Study to NCT01155466 [P04938] and NCT01227265 [P07037] (P06153)
NCT01227265	PHASE3	COMPLETED	Placebo Controlled Study of Preladenant in Participants With Moderate to Severe Parkinson’s Disease (P07037)
NCT00406029	PHASE2	COMPLETED	Dyskinesia in Parkinson’s Disease (Study P04501)
NCT00537017	PHASE2	COMPLETED	Follow Up Safety Study of SCH 420814 in Subjects With Parkinson’s Disease (P05175)
NCT00686699	PHASE2	TERMINATED	Study of Preladenant for the Treatment of Antipsychotic Induced Movement Disorders in Participants With Schizophrenia (Study P04628)
NCT00693472	PHASE2	TERMINATED	Study of Preladenant for the Treatment of Neuroleptic Induced Akathisia (Study P05145)
NCT01294800	PHASE2	COMPLETED	A Dose Finding Study of Preladenant (SCH 420814) for the Treatment of Parkinson’s Disease (PD) in Japanese Patients (P06402)
NCT01323855	PHASE1	COMPLETED	A Study to Assess Pharmacokinetics (PK) of Preladenant in Participants With Chronic Renal Impairment (CRI) (P06512)
NCT01465412	PHASE1	COMPLETED	A Study to Assess Pharmacokinetics of Preladenant in Participants With Chronic Hepatic Impairment (P06513)
NCT03099161	PHASE1	TERMINATED	Study of Preladenant (MK-3814) Alone and With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3814A-062)

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.

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

Molecule	Source	Status	Shared targets
ADENOSINE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA2B, ADORA3
CAFFEINE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA2B, ADORA3
ISTRADEFYLLINE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA2B, ADORA3
REGADENOSON	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA2B, ADORA3
THEOPHYLLINE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA2B, ADORA3
BINODENOSON	ChEMBL	Phase 3	ADORA1, ADORA2A, ADORA2B, ADORA3
ROLOFYLLINE	ChEMBL	Phase 3	ADORA1, ADORA2A, ADORA2B, ADORA3
TONAPOFYLLINE	ChEMBL	Phase 3	ADORA1, ADORA2A, ADORA2B, ADORA3
TOZADENANT	ChEMBL	Phase 3	ADORA1, ADORA2A, ADORA2B, ADORA3
TRABODENOSON	ChEMBL	Phase 3	ADORA1, ADORA2A, ADORA2B, ADORA3
CIFORADENANT	ChEMBL	Phase 2	ADORA1, ADORA2A, ADORA2B, ADORA3
DERENOFYLLINE	ChEMBL	Phase 2	ADORA1, ADORA2A, ADORA2B, ADORA3
ENPROFYLLINE	ChEMBL	Phase 2	ADORA1, ADORA2A, ADORA2B, ADORA3
IMARADENANT	ChEMBL	Phase 2	ADORA1, ADORA2A, ADORA2B, ADORA3
TECADENOSON	ChEMBL	Phase 2	ADORA1, ADORA2A, ADORA2B, ADORA3
VIPADENANT	ChEMBL	Phase 2	ADORA1, ADORA2A, ADORA2B, ADORA3
Fidaxomicin	ChEMBL + PubChem	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
Linagliptin	ChEMBL + PubChem	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
Pyrazinamide	ChEMBL + PubChem	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
CLOFARABINE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
ECONAZOLE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
EPALRESTAT	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
FEDRATINIB	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
MEFLOQUINE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
MICONAZOLE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
NEVIRAPINE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
NIFEDIPINE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
NIMESULIDE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
NISOLDIPINE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
NITAZOXANIDE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
PENTOSTATIN	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
PYRVINIUM	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
RIFAMPIN	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
RIFAXIMIN	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
SUNITINIB	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
TAMOXIFEN	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A, ADORA3
APADENOSON	ChEMBL	Phase 3	ADORA1, ADORA2A, ADORA3
DIACEREIN	ChEMBL	Phase 3	ADORA1, ADORA2A, ADORA3
NAMODENOSON	ChEMBL	Phase 3	ADORA1, ADORA2A, ADORA3
ETRUMADENANT	ChEMBL	Phase 2	ADORA1, ADORA2A, ADORA2B
METRIFUDIL	ChEMBL	Phase 2	ADORA1, ADORA2A, ADORA3
SONEDENOSON	ChEMBL	Phase 2	ADORA1, ADORA2A, ADORA2B
TOFIMILAST	ChEMBL	Phase 2	ADORA1, ADORA2A, ADORA3
Afatinib	PubChem	Approved	ADORA1, ADORA2A, ADORA3
Apixaban	PubChem	Approved	ADORA1, ADORA2A, ADORA3
Binimetinib	PubChem	Approved	ADORA1, ADORA2A, ADORA3
Bosentan	PubChem	Approved	ADORA1, ADORA2A, ADORA3
chenodiol	PubChem	Approved	ADORA1, ADORA2A, ADORA3
Dihydroergotamine	PubChem	Approved	ADORA1, ADORA2A, ADORA3
Fulvestrant	PubChem	Approved	ADORA1, ADORA2A, ADORA3
Imipenem	PubChem	Approved	ADORA1, ADORA2A, ADORA3
Propoxyphene	PubChem	Approved	ADORA1, ADORA2A, ADORA3
ALPIDEM	ChEMBL	Phase 4 (approved)	ADORA1, ADORA3
AMPHETAMINE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A
BALSALAZIDE	ChEMBL	Phase 4 (approved)	ADORA2A, ADORA3
BITHIONOL	ChEMBL	Phase 4 (approved)	ADORA2A, ADORA3
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	ADORA2A, ADORA3
ENASIDENIB	ChEMBL	Phase 4 (approved)	ADORA1, ADORA3