Rolofylline
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Also known as KW 3902KW-3902KW3902MK-7418RolofyllinaSID137275983
Summary
Rolofylline (CHEMBL52333) is a phase-3 clinical-stage small molecule targeting ADORA1, ADORA2A, and ADORA2B; indicated across 2 conditions including heart failure and congestive heart failure.
At a glance
- Status: Max clinical phase 3 (not approved)
- Modality: Small molecule
- Targets: 4 (ADORA1, ADORA2A, ADORA2B…)
- Indications: 2 conditions
- Clinical trials: 4
- Chemistry: 356.5 Da · C20H28N4O2
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL52333 |
| Name | Rolofylline |
| Type | Small molecule |
| Max phase | 3 |
| FDA approved | no |
| PubChem CID | 64627 |
| Molecular formula | C20H28N4O2 |
| Molecular weight | 356.5 |
| InChIKey | PJBFVWGQFLYWCB-UHFFFAOYSA-N |
SMILES: CCCN1C2=C(C(=O)N(C1=O)CCC)NC(=N2)C34CC5CC(C3)CC4C5
IUPAC name: 1,3-dipropyl-8-(3-tricyclo[3.3.1.03,7]nonanyl)-7H-purine-2,6-dione
Also known as: KW 3902, KW-3902, KW3902, MK-7418, Rolofyllina, Rolofylline, ROLOFYLLINE, SID137275983
Patent coverage: 156 distinct patent families (421 SureChEMBL compound mentions), from 2 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 | 9.14 | 0.3% | P30542 |
| ADORA2A | A2A receptor | Antagonist | 6.97 | 0.4% | P29274 |
| ADORA2B | A2B receptor | Antagonist | 6.53 | 0.5% | P29275 |
| ADORA3 | A3 receptor | Antagonist | 5.36 | 0% | P0DMS8 |
Broader ChEMBL bioactivity targets: 16 (assay-derived). Sample: Solute carrier family 22 member 6, Organic anion transporter 3, Solute carrier family 22 member 11, Adenosine A2 receptor, Adenosine A2 receptor, Adenosine receptor A1, Adenosine receptor A1, Sodium-dependent dopamine transporter, Adenosine receptor A2a, Adenosine receptor A2b.
Bioactivity
ChEMBL activities: 39 potent at pChembl ≥ 5 of 40 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| Q60612 | 9.84 | Ki | 0.14 | nM | CHEMBL_ACT_3117557 |
| P25099 | 9.72 | Ki | 0.19 | nM | CHEMBL_ACT_168911 |
| P28190 | 9.72 | Ki | 0.19 | nM | CHEMBL_ACT_202873 |
| P25099 | 9.72 | Ki | 0.19 | nM | CHEMBL_ACT_22459689 |
| P25099 | 9.72 | Ki | 0.19 | nM | CHEMBL_ACT_3117558 |
| ADORA1 | 9.53 | Ki | 0.29 | nM | CHEMBL_ACT_3117559 |
| ADORA1 | 9.15 | Ki | 0.7 | nM | CHEMBL_ACT_22459661 |
| ADORA1 | 9.15 | Ki | 0.7 | nM | CHEMBL_ACT_24772304 |
| ADORA1 | 9.14 | Ki | 0.72 | nM | CHEMBL_ACT_18725591 |
| ADORA1 | 9.14 | Ki | 0.72 | nM | CHEMBL_ACT_654047 |
| P47745 | 8.96 | Ki | 1.1 | nM | CHEMBL_ACT_3116865 |
| P47745 | 8.96 | Ki | 1.1 | nM | CHEMBL_ACT_654045 |
| P47745 | 8.89 | Ki | 1.3 | nM | CHEMBL_ACT_168910 |
| ADORA1 | 8.89 | Ki | 1.3 | nM | CHEMBL_ACT_24973098 |
| P47745 | 8.89 | Ki | 1.3 | nM | CHEMBL_ACT_277321 |
| P25099 | 8.89 | Ki | 1.3 | nM | CHEMBL_ACT_747021 |
| P47745 | 8.89 | Ki | 1.3 | nM | CHEMBL_ACT_847778 |
| ADORA1 | 7.94 | Kd | 11.38 | nM | CHEMBL_ACT_16914152 |
| P25099 | 7.9 | Ki | 12.6 | nM | CHEMBL_ACT_654046 |
| ADORA2A | 7.46 | Kd | 34.81 | nM | CHEMBL_ACT_16914929 |
| ADORA2A | 6.97 | Ki | 108 | nM | CHEMBL_ACT_18725596 |
| ADORA2A | 6.97 | Ki | 108 | nM | CHEMBL_ACT_22459724 |
| ADORA2A | 6.97 | Ki | 108 | nM | CHEMBL_ACT_654050 |
| ADORA2A | 6.88 | Kd | 131.2 | nM | CHEMBL_ACT_16914916 |
| P30543 | 6.77 | Ki | 170 | nM | CHEMBL_ACT_3116864 |
| P46616 | 6.64 | Ki | 230 | nM | CHEMBL_ACT_3116863 |
| ADORA2A | 6.64 | Ki | 230 | nM | CHEMBL_ACT_654048 |
| ADORA2B | 6.57 | Ki | 269 | nM | CHEMBL_ACT_18725601 |
| ADORA2B | 6.53 | Ki | 296 | nM | CHEMBL_ACT_22459783 |
| P29276 | 6.42 | Ki | 380 | nM | CHEMBL_ACT_168912 |
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
2 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 |
|---|---|---|---|
| heart failure | 3 | MONDO:0005252 | EFO:0003144 |
| congestive heart failure | 3 | MONDO:0005009 | EFO:0000373 |
Clinical trials
Total trials: 4.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE3 | 3 |
| PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00328692 | PHASE3 | COMPLETED | PROTECT-1: A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function |
| NCT00354458 | PHASE3 | COMPLETED | PROTECT-2: A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function |
| NCT00443690 | PHASE3 | COMPLETED | Placebo-Controlled Randomized Study of KW-3902 for Subjects Hospitalized With Worsening Renal Function and Heart Failure Requiring IV Therapy |
| NCT00729222 | PHASE2 | COMPLETED | Hemodynamic Effects of Rolofylline in the Treatment of Patients With Heart Failure (7418-503) |
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 |
| 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 |
| ERLOTINIB | ChEMBL | Phase 4 (approved) | ADORA2A, ADORA3 |
Related Atlas pages
- Genes: ADORA1, ADORA2A, ADORA2B, ADORA3
- Diseases: heart failure, congestive heart failure
- Drugs: Adenosine, Caffeine, Istradefylline, Regadenoson, Theophylline, Binodenoson, Tonapofylline, Tozadenant, Trabodenoson, Fidaxomicin, Linagliptin, Pyrazinamide, Clofarabine, Clotrimazole, Diethylstilbestrol, Econazole, Epalrestat, Fedratinib, Mefloquine, Miconazole, Nevirapine, Nifedipine, Nimesulide, Nisoldipine, Nitazoxanide, Pentostatin, Pyrvinium, Rifampin, Rifaximin, Sunitinib, Tamoxifen, Apadenoson, Diacerein, Namodenoson, Afatinib, Apixaban, Binimetinib, Bosentan, chenodiol, Dihydroergotamine, Fulvestrant, Imipenem, Propoxyphene, Alpidem, Amphetamine, Balsalazide, Bithionol, Daunorubicin, Enasidenib, Erlotinib