Pelabresib

Summary

Pelabresib (CHEMBL4303404) is a phase-3 clinical-stage small-molecule antineoplastic agent (ATC L01XX84) targeting BRD4; indicated across 6 conditions including neoplasm and peripheral nervous system neoplasm.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: L01XX84
• Targets: 1 (BRD4)
• Indications: 6 conditions
• Clinical trials: 11
• Chemistry: 365.8 Da · C20H16ClN3O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4303404
Name	Pelabresib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	57389999
ChEBI	CHEBI:189653
ATC	L01XX84
Molecular formula	C20H16ClN3O2
Molecular weight	365.8
InChIKey	GCWIQUVXWZWCLE-INIZCTEOSA-N

SMILES: CC1=NOC2=C1C3=CC=CC=C3C(=N[C@H]2CC(=O)N)C4=CC=C(C=C4)Cl

IUPAC name: 2-[(4S)-6-(4-chlorophenyl)-1-methyl-4H-[1,2]oxazolo[5,4-d][2]benzazepin-4-yl]acetamide

ChEBI definition: An organic heterotricyclic compound that is 4H-[1,2]oxazolo[5,4-d][2]benzazepine substituted by methyl, 2-amino-2-oxoethyl, and 4-chlorophenyl groups at positions 1, 4S and 6, respectively. It is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins and exhibits antineoplastic activity.

Pharmacological roles (ChEBI): antineoplastic agent, bromodomain-containing protein 4 inhibitor.

Also known as: Cpi 0610, Cpi-0610, CPI-0610, Cpi-0610 anhydrous, CPI-232, CPI-267232, Pelabresib, Pelabresib anhydrous, Pelabresib monohydrate, CPI 0610, PELABRESIB, PELABRESIB ANHYDROUS

Patent coverage: 567 distinct patent families (1,513 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,489 (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
BRD4	bromodomain containing 4	Inhibition	7.41	94.7% (common-essential)	O60885

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Bromodomain-containing protein 4.

Bioactivity

ChEMBL activities: 8 potent at pChembl ≥ 5 of 8 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
BRD4	8.52	IC50	3	nM	CHEMBL_ACT_24727648
BRD4	7.96	IC50	11	nM	CHEMBL_ACT_24727647
BRD4	7.75	IC50	18	nM	CHEMBL_ACT_18293304
BRD4	7.41	IC50	39	nM	CHEMBL_ACT_18951335
BRD4	7.41	IC50	39	nM	CHEMBL_ACT_18997188
BRD4	7.41	IC50	39	nM	CHEMBL_ACT_25007373
BRD4	7.41	IC50	39	nM	CHEMBL_ACT_25071509
BRD4	6.75	EC50	180	nM	CHEMBL_ACT_25071484

Target pathways

Aggregated over 1 target gene(s): BRD4.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Disease	1	BRD4
Infectious disease	1	BRD4
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	1
regulation of transcription by RNA polymerase II	1
DNA damage response	1
positive regulation of G2/M transition of mitotic cell cycle	1
positive regulation of transcription elongation by RNA polymerase II	1
positive regulation of canonical NF-kappaB signal transduction	1
host-mediated suppression of viral transcription	1
positive regulation of DNA-templated transcription	1
positive regulation of transcription by RNA polymerase II	1
regulation of inflammatory response	1
negative regulation of DNA damage checkpoint	1
positive regulation of T-helper 17 cell lineage commitment	1
chromatin organization	1
regulation of DNA-templated transcription	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
neoplasm	3	MONDO:0005070	EFO:0000616
peripheral nervous system neoplasm	2	MONDO:0001406	EFO:0002431
lymphoma	1	MONDO:0005062	EFO:0000574
plasma cell myeloma	1	MONDO:0009693	EFO:0001378
primary myelofibrosis	1	MONDO:0009692	MONDO:0044903

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 11.

Phase distribution

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

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04603495	PHASE3	ACTIVE_NOT_RECRUITING	Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2)
NCT06401356	PHASE3	RECRUITING	An Extension Study for Patients Previously Enrolled in Studies With Pelabresib
NCT07357727	PHASE3	RECRUITING	A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)
NCT02158858	PHASE1/PHASE2	COMPLETED	A Phase 1/2 Study of CPI-0610 With and Without Ruxolitinib in Patients With Hematologic and Myeloproliferative Malignancies
NCT02986919	PHASE2	WITHDRAWN	Study of CPI-0610 in Patients With Malignant Peripheral Nerve Sheath Tumors
NCT07340138	PHASE1	RECRUITING	Study of Pelabresib add-on to Ruxolitinib in Japanese Adult Patients With Myelofibrosis
NCT07340190	PHASE1	NOT_YET_RECRUITING	A Drug-drug Interaction Study to Evaluate the Effects of Pelabresib on the Pharmacokinetics of Repaglinide, Midazolam, and Combined Oral Contraceptive in Patients With Advanced Malignancies
NCT07422610	PHASE1	RECRUITING	Pharmacokinetics and Safety Study of Pelabresib in Patients With Advanced Malignancies and Hepatic Impairment
NCT01949883	PHASE1	COMPLETED	A Phase 1 Study Evaluating CPI-0610 in Patients With Progressive Lymphoma
NCT02157636	PHASE1	COMPLETED	A Phase 1 Study Evaluating CPI-0610 in Patients With Previously Treated Multiple Myeloma
NCT05391022	PHASE1	COMPLETED	Study Evaluating Food Effect and QTc in Patients With Advanced Malignancies

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.

24 molecules share ≥1 primary target. Top 24 by shared-target count:

Molecule	Source	Status	Shared targets
ACETAMINOPHEN	ChEMBL	Phase 4 (approved)	BRD4
ALPRAZOLAM	ChEMBL	Phase 4 (approved)	BRD4
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
VORINOSTAT	ChEMBL	Phase 4 (approved)	BRD4
APABETALONE	ChEMBL	Phase 3	BRD4
DINACICLIB	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
BIRABRESIB	ChEMBL	Phase 2	BRD4
CLOXYQUIN	ChEMBL	Phase 2	BRD4
EZOBRESIB	ChEMBL	Phase 2	BRD4
MIVEBRESIB	ChEMBL	Phase 2	BRD4
MOLIBRESIB	ChEMBL	Phase 2	BRD4
SF-1126	ChEMBL	Phase 2	BRD4