Tonapofylline

Summary

Tonapofylline (CHEMBL414157) is a phase-3 clinical-stage small molecule targeting ADORA1, ADORA2A, and ADORA2B; indicated across 4 conditions including congestive heart failure and heart failure.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 4 (ADORA1, ADORA2A, ADORA2B…)
• Indications: 4 conditions
• Clinical trials: 3
• Chemistry: 416.5 Da · C22H32N4O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL414157
Name	Tonapofylline
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	216466
Molecular formula	C22H32N4O4
Molecular weight	416.5
InChIKey	ZWTVVWUOTJRXKM-UHFFFAOYSA-N

SMILES: CCCN1C2=C(C(=O)N(C1=O)CCC)NC(=N2)C34CCC(CC3)(CC4)CCC(=O)O

IUPAC name: 3-[4-(2,6-dioxo-1,3-dipropyl-7H-purin-8-yl)-1-bicyclo[2.2.2]octanyl]propanoic acid

Also known as: BG-9928, BG9928, Tonapofilina, Tonapofylline, TONAPOFYLLINE

Parent form; salt/anhydrous children: CHEMBL535165

Patent coverage: 77 distinct patent families (216 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 211 (98%) 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
ADORA1	A1 receptor	Antagonist	8.13	0.3%	P30542
ADORA2A	A2A receptor	Antagonist	5.19	0.4%	P29274
ADORA2B	A2B receptor	Antagonist	7.05	0.5%	P29275
ADORA3	A3 receptor	Antagonist	5	0%	P0DMS8

Broader ChEMBL bioactivity targets: 6 (assay-derived). Sample: Adenosine receptor A1, Adenosine receptor A2a, Adenosine receptor A2b, Adenosine receptor A3, Adenosine receptor A2a, Adenosine receptor A1.

Bioactivity

ChEMBL activities: 11 potent at pChembl ≥ 5 of 11 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P25099	9.8	Kd	0.16	nM	CHEMBL_ACT_1781217
P25099	9	Ki	1	nM	CHEMBL_ACT_1781139
P25099	8.89	Ki	1.3	nM	CHEMBL_ACT_3116844
ADORA1	8.15	Ki	7	nM	CHEMBL_ACT_1781151
ADORA1	8.13	Ki	7.4	nM	CHEMBL_ACT_3116848
ADORA2B	7.05	Ki	90	nM	CHEMBL_ACT_1781153
ADORA2B	7.05	Ki	90	nM	CHEMBL_ACT_3116846
P30543	5.61	Ki	2440	nM	CHEMBL_ACT_3116843
ADORA2A	5.19	Ki	6400	nM	CHEMBL_ACT_1781152
ADORA2A	5.19	Ki	6410	nM	CHEMBL_ACT_3116847
ADORA3	5	Ki	10000	nM	CHEMBL_ACT_3116845

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

4 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
congestive heart failure	3	MONDO:0005009	EFO:0000373
heart failure	3	MONDO:0005252	EFO:0003144
kidney failure	3	MONDO:0001106	HP:0000083
liver disorder	1	MONDO:0005154	EFO:0001421

Clinical trials

Total trials: 3.

Phase distribution

Phase	Trials
PHASE3	1
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00709865	PHASE3	COMPLETED	Study to Assess the Safety and Tolerability of IV Tonapofylline in Subjects With Acute Decompensated Heart Failure (ADHF) and Renal Insufficiency
NCT00745316	PHASE2	TERMINATED	Oral Tonapofylline (BG9928) in Patients With Heart Failure and Renal Insufficiency
NCT00858156	PHASE1	COMPLETED	BG9928 in Subjects With Hepatic Impairment

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 100 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
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
ERLOTINIB	ChEMBL	Phase 4 (approved)	ADORA2A, ADORA3
ETHINYL ESTRADIOL	ChEMBL	Phase 4 (approved)	ADORA2A, ADORA3
GENTIAN VIOLET	ChEMBL	Phase 4 (approved)	ADORA2A, ADORA3
GLAFENINE	ChEMBL	Phase 4 (approved)	ADORA2A, ADORA3
HALOPROGIN	ChEMBL	Phase 4 (approved)	ADORA1, ADORA3
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	ADORA2A, ADORA3
HYDROXOCOBALAMIN	ChEMBL	Phase 4 (approved)	ADORA1, ADORA3
IBRUTINIB	ChEMBL	Phase 4 (approved)	ADORA2A, ADORA3
IBUDILAST	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A
INDOCYANINE GREEN ACID FORM	ChEMBL	Phase 4 (approved)	ADORA1, ADORA3
LANSOPRAZOLE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA3
LOVASTATIN	ChEMBL	Phase 4 (approved)	ADORA1, ADORA3
OSIMERTINIB	ChEMBL	Phase 4 (approved)	ADORA2A, ADORA3
PEXIDARTINIB	ChEMBL	Phase 4 (approved)	ADORA1, ADORA3
RABEPRAZOLE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA3
RALOXIFENE	ChEMBL	Phase 4 (approved)	ADORA2A, ADORA3
SILDENAFIL	ChEMBL	Phase 4 (approved)	ADORA1, ADORA2A
TOLCAPONE	ChEMBL	Phase 4 (approved)	ADORA1, ADORA3
VALDECOXIB	ChEMBL	Phase 4 (approved)	ADORA1, ADORA3
VARDENAFIL	ChEMBL	Phase 4 (approved)	ADORA1, ADORA3
DEFACTINIB	ChEMBL	Phase 3	ADORA2A, ADORA3
OTILONIUM BROMIDE	ChEMBL	Phase 3	ADORA2A, ADORA3
PRELADENANT	ChEMBL	Phase 3	ADORA1, ADORA2A
QUINFAMIDE	ChEMBL	Phase 3	ADORA1, ADORA3
DENBUFYLLINE	ChEMBL	Phase 2	ADORA2A, ADORA2B
GENISTEIN	ChEMBL	Phase 2	ADORA1, ADORA2A
NOCODAZOLE	ChEMBL	Phase 2	ADORA1, ADORA2A
PSILOCIN	ChEMBL	Phase 2	ADORA2A, ADORA2B
Selumetinib	PubChem	Approved	ADORA2A, ADORA3
Tafamidis	PubChem	Approved	ADORA1, ADORA2A
VORAPAXAR	ChEMBL + PubChem	Phase 4 (approved)	ADORA3
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	ADORA3
ACEFYLLINE	ChEMBL	Phase 4 (approved)	ADORA2B
ALECTINIB	ChEMBL	Phase 4 (approved)	ADORA3
ALFACALCIDOL	ChEMBL	Phase 4 (approved)	ADORA3
ALLOPURINOL	ChEMBL	Phase 4 (approved)	ADORA2A
AMILORIDE	ChEMBL	Phase 4 (approved)	ADORA2A
AMIODARONE	ChEMBL	Phase 4 (approved)	ADORA3
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	ADORA3
AMLODIPINE	ChEMBL	Phase 4 (approved)	ADORA3
AMOROLFINE	ChEMBL	Phase 4 (approved)	ADORA3