Apabetalone

Summary

Apabetalone (CHEMBL2393130) is a phase-3 clinical-stage small molecule targeting BRD2, BRD4, and BRD3; indicated across 6 conditions including coronary artery disorder and diabetes mellitus.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 3 (BRD2, BRD4, BRD3)
• Indications: 6 conditions
• Clinical trials: 13

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2393130
Name	Apabetalone
Type	Small molecule
Max phase	3

Also known as: Apabetalona, Apabetalone, RVX-000222, RVX-208, RVX000222, APABETALONE, RVX-208(RVX-000222)

Patent coverage: 552 distinct patent families (1,350 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 1,122 (83%) 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
BRD2	bromodomain containing 2	Antagonist	7.05	39%	P25440
BRD4	bromodomain containing 4	Antagonist	7.4	94.7% (common-essential)	O60885
BRD3	bromodomain containing 3	Antagonist	6.55	0%	Q15059

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Bromodomain-containing protein 4, Bromodomain-containing protein 2, Bromodomain testis-specific protein, Bromodomain-containing protein 3, Protein deacetylase HDAC6.

Bioactivity

ChEMBL activities: 106 potent at pChembl ≥ 5 of 110 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
BRD4	7.4	IC50	40	nM	CHEMBL_ACT_19057707
BRD4	7.36	IC50	43.8	nM	CHEMBL_ACT_19195163
BRD4	7.3	IC50	50	nM	CHEMBL_ACT_29217878
BRD4	7.17	IC50	67	nM	CHEMBL_ACT_18207822
BRD4	7	IC50	100	nM	CHEMBL_ACT_19211469
BRD4	6.91	IC50	124.2	nM	CHEMBL_ACT_29310547
BRD4	6.89	Kd	130	nM	CHEMBL_ACT_18871515
BRD4	6.89	Kd	130	nM	CHEMBL_ACT_29217978
BRD4	6.88	IC50	132	nM	CHEMBL_ACT_24403855
BRD4	6.87	Kd	135	nM	CHEMBL_ACT_18201041
BRD4	6.87	IC50	135	nM	CHEMBL_ACT_18416355
BRD4	6.87	Kd	135	nM	CHEMBL_ACT_19014805
BRD4	6.87	Kd	135	nM	CHEMBL_ACT_19267658
BRD4	6.87	Kd	135	nM	CHEMBL_ACT_22397736
BRD4	6.87	Kd	135	nM	CHEMBL_ACT_24727650
BRD4	6.87	Kd	135	nM	CHEMBL_ACT_24813739
BRD4	6.87	Kd	135	nM	CHEMBL_ACT_25007377
BRD4	6.87	Ki	135	nM	CHEMBL_ACT_25572931
BRD4	6.87	Kd	135	nM	CHEMBL_ACT_25925697
BRD4	6.87	Kd	135	nM	CHEMBL_ACT_25925708
BRD4	6.87	IC50	135	nM	CHEMBL_ACT_28511186
BRD4	6.85	Kd	140	nM	CHEMBL_ACT_16493448
BRD4	6.85	Kd	140	nM	CHEMBL_ACT_16535673
BRD4	6.85	IC50	140	nM	CHEMBL_ACT_25002325
BRD3	6.72	Kd	190	nM	CHEMBL_ACT_18871525
BRD3	6.71	Kd	195	nM	CHEMBL_ACT_18201140
BRD4	6.7	Kd	200	nM	CHEMBL_ACT_24426572
BRD2	6.69	Kd	206	nM	CHEMBL_ACT_16493446
BRD3	6.69	IC50	203	nM	CHEMBL_ACT_18416371
BRD3	6.69	Kd	203	nM	CHEMBL_ACT_19267682

Target pathways

Aggregated over 3 target gene(s): BRD2, BRD4, BRD3.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
Disease	1	BRD4
Generic Transcription Pathway	1	BRD2
Infectious disease	1	BRD4
RNA Polymerase II Transcription	1	BRD2
Gene expression (Transcription)	1	BRD2
Transcriptional regulation by RUNX3	1	BRD2
RUNX3 regulates p14-ARF	1	BRD2
Potential therapeutics for SARS	1	BRD4
SARS-CoV Infections	1	BRD4
Viral Infection Pathways	1	BRD4
Regulation of PD-L1(CD274) transcription	1	BRD4

Dominant GO biological processes

GO term	Targets
chromatin remodeling	3
regulation of transcription by RNA polymerase II	3
chromatin organization	3
regulation of DNA-templated transcription	3
protein localization to chromatin	2
positive regulation of T-helper 17 cell lineage commitment	2
positive regulation of transcription by RNA polymerase II	2
neural tube closure	1
nucleosome assembly	1
spermatogenesis	1
chromatin looping	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of gene expression	1
T-helper 17 cell lineage commitment	1
DNA damage response	1

Indications & clinical

Indications

6 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
coronary artery disorder	3	MONDO:0005010	EFO:0001645
diabetes mellitus	2	MONDO:0005015	EFO:0000400
pulmonary arterial hypertension	2	MONDO:0015924	EFO:0001361
severe acute respiratory syndrome	2	MONDO:0005091	MONDO:0100096
Fabry disease	1	MONDO:0010526	MONDO:0010526
chronic kidney disease	1	MONDO:0005300	MONDO:0024327

Clinical trials

Total trials: 13.

Phase distribution

Phase	Trials
PHASE2	6
PHASE1/PHASE2	3
PHASE2/PHASE3	2
PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06590324	PHASE2/PHASE3	RECRUITING	A Study of Apabetalone in Subjects With Long -COVID
NCT02586155	PHASE3	COMPLETED	Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk T2DM Subjects With CAD
NCT04894266	PHASE2/PHASE3	TERMINATED	An Open-Label Study of Apabetalone in Covid Infection
NCT03160430	PHASE1/PHASE2	NOT_YET_RECRUITING	A Two-Part Phase 2a Study of RVX000222 in Patients With End-Stage Renal Disease Treated With Hemodialysis
NCT00768274	PHASE1/PHASE2	COMPLETED	Safety, Pharmacokinetic Study of RVX000222 in Healthy Subjects and Subjects With Low HDL Cholesterol
NCT01058018	PHASE2	COMPLETED	Clinical Trial for Dose Finding and Safety of RVX000222 in Subjects With Stable Coronary Artery Disease
NCT01067820	PHASE2	COMPLETED	ApoA-I Synthesis Stimulation and Intravascular Ultrasound for Coronary Atheroma Regression Evaluation
NCT01423188	PHASE2	COMPLETED	The Study of Quantitative Serial Trends in Lipids With ApolpoproteinA-I Stimulation
NCT01728467	PHASE2	COMPLETED	The Effects of RVX000222 on Glucose Metabolism in Individuals With Pre-diabetes
NCT01863225	PHASE2	TERMINATED	Characterization of Multi-dose RVX000222 in Combination With Statin Treatment in Dyslipidemia
NCT03228940	PHASE1/PHASE2	WITHDRAWN	Safety and Effect of Oral RVX000222 in Subjects With Fabry Disease
NCT04915300	PHASE2	UNKNOWN	Apabetalone for Pulmonary Arterial Hypertension
NCT03655704	EARLY_PHASE1	COMPLETED	Apabetalone for Pulmonary Arterial Hypertension: a Pilot Study

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.

29 molecules share ≥1 primary target. Top 29 by shared-target count:

Molecule	Source	Status	Shared targets
Acetaminophen	ChEMBL + PubChem	Phase 4 (approved)	BRD2, BRD3, BRD4
Alprazolam	ChEMBL + PubChem	Phase 4 (approved)	BRD2, BRD3, BRD4
Vorinostat	ChEMBL + PubChem	Phase 4 (approved)	BRD2, BRD3, BRD4
BIRABRESIB	ChEMBL	Phase 2	BRD2, BRD3, BRD4
EZOBRESIB	ChEMBL	Phase 2	BRD2, BRD3, BRD4
MIVEBRESIB	ChEMBL	Phase 2	BRD2, BRD3, BRD4
MOLIBRESIB	ChEMBL	Phase 2	BRD2, BRD3, BRD4
Bortezomib	PubChem	Approved	BRD2, BRD3
Estazolam	PubChem	Approved	BRD2, BRD3
methylpyrrolidone	PubChem	Approved	BRD2, BRD3
Midazolam	PubChem	Approved	BRD2, BRD3
Triazolam	PubChem	Approved	BRD2, BRD3
BELINOSTAT	ChEMBL	Phase 4 (approved)	BRD4
FEDRATINIB	ChEMBL	Phase 4 (approved)	BRD4
LENALIDOMIDE	ChEMBL	Phase 4 (approved)	BRD4
NITROXOLINE	ChEMBL	Phase 4 (approved)	BRD4
NORFLOXACIN	ChEMBL	Phase 4 (approved)	BRD4
PANOBINOSTAT	ChEMBL	Phase 4 (approved)	BRD4
ROMIDEPSIN	ChEMBL	Phase 4 (approved)	BRD4
DINACICLIB	ChEMBL	Phase 3	BRD4
PELABRESIB	ChEMBL	Phase 3	BRD4
TACEDINALINE	ChEMBL	Phase 3	BRD4
VOLASERTIB	ChEMBL	Phase 3	BRD4
7-ETHYL-10-HYDROXYCAMPTOTHECIN	ChEMBL	Phase 2	BRD4
ALOBRESIB	ChEMBL	Phase 2	BRD4
AMREDOBRESIB	ChEMBL	Phase 2	BRD4
BI-2536	ChEMBL	Phase 2	BRD4
CLOXYQUIN	ChEMBL	Phase 2	BRD4
SF-1126	ChEMBL	Phase 2	BRD4