Pracinostat

Summary

Pracinostat (CHEMBL1851943) is a phase-3 clinical-stage small-molecule EC 3.5.1.98 (histone deacetylase) inhibitor targeting HDAC10, HDAC3, and HDAC1; indicated across 7 conditions including acute myeloid leukemia and myelodysplastic syndrome.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 4 (HDAC10, HDAC3, HDAC1…)
• Indications: 7 conditions
• Clinical trials: 13
• Chemistry: 358.5 Da · C20H30N4O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1851943
Name	Pracinostat
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	49855250
ChEBI	CHEBI:95071
Molecular formula	C20H30N4O2
Molecular weight	358.5
InChIKey	JHDKZFFAIZKUCU-ZRDIBKRKSA-N

SMILES: CCCCC1=NC2=C(N1CCN(CC)CC)C=CC(=C2)/C=C/C(=O)NO

IUPAC name: (E)-3-[2-butyl-1-[2-(diethylamino)ethyl]benzimidazol-5-yl]-N-hydroxyprop-2-enamide

ChEBI definition: A hydroxamic acid that is N-hydroxyacrylamide which is substituted at position 3 by a 2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl group (the E isomer). An orally available pan-histone deacetylase inhibitor with demonstrated activity in the treatment of advanced solid tumours.

Pharmacological roles (ChEBI): EC 3.5.1.98 (histone deacetylase) inhibitor, antineoplastic agent, apoptosis inducer, antimalarial.

Also known as: Pracinostat, SB 939, SB-939, Sb939, PRACINOSTAT, SB939 (PRACINOSTAT), Pracinostat hydrochlorideÊ, SB939 (Pracinostat), Pracinostat hydrochlorideÂ

Parent form; salt/anhydrous children: CHEMBL3215861

Patent coverage: 790 distinct patent families (1,998 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,863 (93%) 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
HDAC10	histone deacetylase 10	Inhibition	7.4	0%	Q969S8
HDAC3	histone deacetylase 3	Inhibition	7.37	95.1% (common-essential)	O15379
HDAC1	histone deacetylase 1	Inhibition	7.31	4.5%	Q13547
HDAC5	histone deacetylase 5	Inhibition	7.33	0.5%	Q9UQL6

Broader ChEMBL bioactivity targets: 13 (assay-derived). Sample: Histone deacetylase 3, Protein deacetylase HDAC6, Histone deacetylase 2, Histone deacetylase, Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2), Histone deacetylase 5, Histone deacetylase 7, Histone deacetylase 8, Histone deacetylase 1, Histone deacetylase 11, Histone deacetylase 4, Histone deacetylase 9, Polyamine deacetylase HDAC10.

Bioactivity

ChEMBL activities: 27 potent at pChembl ≥ 5 of 27 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HDAC8	7.8	Ki	16	nM	CHEMBL_ACT_14927527
HDAC2	7.8	Ki	16	nM	CHEMBL_ACT_14927528
HDAC1	7.8	Ki	16	nM	CHEMBL_ACT_14927529
HDAC4	7.8	Ki	16	nM	CHEMBL_ACT_15656437
HDAC3	7.72	Ki	19	nM	CHEMBL_ACT_15656381
HDAC5	7.68	Ki	21	nM	CHEMBL_ACT_15656445
HDAC10	7.64	Ki	23	nM	CHEMBL_ACT_15656477
HDAC9	7.62	Ki	24	nM	CHEMBL_ACT_15656462
HDAC2	7.57	Ki	27	nM	CHEMBL_ACT_15656391
HDAC1	7.55	Ki	28	nM	CHEMBL_ACT_15656401
HDAC11	7.37	Ki	43	nM	CHEMBL_ACT_15656480
HDAC8	7.32	Ki	48	nM	CHEMBL_ACT_15656428
HDAC1	7.3	IC50	50	nM	CHEMBL_ACT_22780913
HDAC3	7.16	IC50	70	nM	CHEMBL_ACT_22780927
HDAC10	7.09	IC50	82	nM	CHEMBL_ACT_22780976
HDAC6	7.03	IC50	93	nM	CHEMBL_ACT_22780948
HDAC7	6.97	Ki	107	nM	CHEMBL_ACT_15656454
HDAC3	6.9	IC50	126	nM	CHEMBL_ACT_13513670
HDAC8	6.85	IC50	140	nM	CHEMBL_ACT_20627601
HDAC6	6.73	IC50	186.1	nM	CHEMBL_ACT_23140985
HDAC6	6.61	Ki	247	nM	CHEMBL_ACT_15656472
HDAC2	6.54	IC50	290	nM	CHEMBL_ACT_22780920
HDAC6	6.48	IC50	334	nM	CHEMBL_ACT_23140993
HDAC10	5.8	IC50	1585	nM	CHEMBL_ACT_19177252
HDAC8	5.55	IC50	2835	nM	CHEMBL_ACT_22780962
HDAC10	5.5	IC50	3162	nM	CHEMBL_ACT_19177281
HDAC5	5.29	IC50	5113	nM	CHEMBL_ACT_22780941

Target pathways

Aggregated over 4 target gene(s): HDAC10, HDAC3, HDAC1, HDAC5.

Top Reactome pathways

57 total, by targets touching each:

Pathway	Targets	Genes
NOTCH1 Intracellular Domain Regulates Transcription	4	HDAC1, HDAC10, HDAC3, HDAC5
Constitutive Signaling by NOTCH1 PEST Domain Mutants	4	HDAC1, HDAC10, HDAC3, HDAC5
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	4	HDAC1, HDAC10, HDAC3, HDAC5
Notch-HLH transcription pathway	4	HDAC1, HDAC10, HDAC3, HDAC5
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	4	HDAC1, HDAC10, HDAC3, HDAC5
HDACs deacetylate histones	3	HDAC1, HDAC10, HDAC3
Regulation of PTEN gene transcription	3	HDAC1, HDAC3, HDAC5
p75NTR negatively regulates cell cycle via SC1	2	HDAC1, HDAC3
Regulation of MECP2 expression and activity	2	HDAC1, HDAC3
STAT3 nuclear events downstream of ALK signaling	2	HDAC1, HDAC3
Transcription of E2F targets under negative control by DREAM complex	1	HDAC1
Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1	1	HDAC1
G0 and Early G1	1	HDAC1
PPARA activates gene expression	1	HDAC3
Formation of the beta-catenin:TCF transactivating complex	1	HDAC1
Transcriptional activation of mitochondrial biogenesis	1	HDAC3
Downregulation of SMAD2/3:SMAD4 transcriptional activity	1	HDAC1
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	1	HDAC1
Deactivation of the beta-catenin transactivating complex	1	HDAC1
Transcriptional regulation of white adipocyte differentiation	1	HDAC3
Association of TriC/CCT with target proteins during biosynthesis	1	HDAC3
Regulation of lipid metabolism by PPARalpha	1	HDAC3
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	1	HDAC1
NoRC negatively regulates rRNA expression	1	HDAC1
SUMOylation of chromatin organization proteins	1	HDAC1
Repression of WNT target genes	1	HDAC1
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	HDAC3
Regulation of TP53 Activity through Acetylation	1	HDAC1
G1/S-Specific Transcription	1	HDAC1
RNA Polymerase I Transcription Initiation	1	HDAC1
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	HDAC1
RUNX2 regulates osteoblast differentiation	1	HDAC3
Estrogen-dependent gene expression	1	HDAC1
Loss of MECP2 binding ability to the NCoR/SMRT complex	1	HDAC3
Loss of MECP2 binding ability to 5mC-DNA	1	HDAC1
MECP2 regulates neuronal receptors and channels	1	HDAC1
MECP2 regulates transcription of neuronal ligands	1	HDAC1
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1	HDAC3
HCMV Early Events	1	HDAC3
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1	HDAC1
Potential therapeutics for SARS	1	HDAC1
Cytoprotection by HMOX1	1	HDAC3
Heme signaling	1	HDAC3
Nuclear events stimulated by ALK signaling in cancer	1	HDAC1
Negative Regulation of CDH1 Gene Transcription	1	HDAC1
Regulation of MITF-M-dependent genes involved in apoptosis	1	HDAC1
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1	HDAC1
Factors involved in megakaryocyte development and platelet production	1	HDAC1
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	HDAC3
Regulation of endogenous retroelements by KRAB-ZFP proteins	1	HDAC1

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	4
chromatin organization	4
negative regulation of DNA-templated transcription	4
positive regulation of transcription by RNA polymerase II	3
protein deacetylation	2
response to xenobiotic stimulus	2
circadian regulation of gene expression	2
epigenetic regulation of gene expression	2
negative regulation of apoptotic process	2
rhythmic process	2
neuron differentiation	2
negative regulation of gene expression, epigenetic	2
DNA repair	1
regulation of DNA-templated transcription	1
macroautophagy	1

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
acute myeloid leukemia	3	MONDO:0018874	EFO:0000222
myelodysplastic syndrome	2	MONDO:0018881	EFO:0000198
sarcoma	2	MONDO:0005089	EFO:0000691
neoplasm	1	MONDO:0005070	EFO:0000616

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

Clinical trials

Total trials: 13.

Phase distribution

Phase	Trials
PHASE2	7
PHASE1	4
PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03151408	PHASE3	TERMINATED	An Efficacy and Safety Study Of Pracinostat In Combination With Azacitidine In Adults With Acute Myeloid Leukemia
NCT01112384	PHASE2	COMPLETED	A Study of SB939 in Patients With Translocation-Associated Recurrent/Metastatic Sarcomas
NCT01200498	PHASE2	COMPLETED	Study of SB939 in Subjects With Myelofibrosis
NCT01873703	PHASE2	COMPLETED	Phase 2 Study of Pracinostat With Azacitidine in Patients With Previously Untreated Myelodysplastic Syndrome
NCT01912274	PHASE2	COMPLETED	Safety and Efficacy Study of Pracinostat With Azacitadine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
NCT01993641	PHASE2	COMPLETED	Phase 2 Study Adding Pracinostat to a Hypomethylating Agent (HMA) in Patients With MDS Who Failed to Respond to Single Agent HMA
NCT02267278	PHASE2	COMPLETED	Ruxolitinib and Pracinostat Combination Therapy for Patients With Myelofibrosis (MF)
NCT03151304	PHASE2	TERMINATED	A Safety and Efficacy Study of Pracinostat and Azacitidine in Patients With High Risk Myelodysplastic Syndromes
NCT00741234	PHASE1	COMPLETED	A Phase I Dose Escalation Study of Oral SB939 Administered Alone or With Azacitidine
NCT01184274	PHASE1	COMPLETED	A Phase I Study of SB939 in Pediatric Patients With Refractory Solid Tumours and Leukemia
NCT02118909	PHASE1	COMPLETED	Evaluate the Effects of Itraconazole and Ciprofloxacin on Single-Dose PK of Pracinostat in Healthy Nonsmoking Subjects
NCT03495934	PHASE1	COMPLETED	A Study In Healthy Male Volunteers Designed To Investigate How A Radiolabelled Medicine Is Broken Down And Removed From The Body
NCT02058784	EARLY_PHASE1	COMPLETED	Study to Evaluate the Food Effect of Single-dose Bioavailability of Pracinostat in Healthy Adult Subjects

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.

47 molecules share ≥1 primary target. Top 47 by shared-target count:

Molecule	Source	Status	Shared targets
BELINOSTAT	ChEMBL	Phase 4 (approved)	HDAC1, HDAC10, HDAC3, HDAC5
BENDAMUSTINE	ChEMBL	Phase 4 (approved)	HDAC1, HDAC10, HDAC3, HDAC5
CELECOXIB	ChEMBL	Phase 4 (approved)	HDAC1, HDAC10, HDAC3, HDAC5
GIVINOSTAT	ChEMBL	Phase 4 (approved)	HDAC1, HDAC10, HDAC3, HDAC5
PANOBINOSTAT	ChEMBL	Phase 4 (approved)	HDAC1, HDAC10, HDAC3, HDAC5
PHENYLBUTANOIC ACID	ChEMBL	Phase 4 (approved)	HDAC1, HDAC10, HDAC3, HDAC5
ROMIDEPSIN	ChEMBL	Phase 4 (approved)	HDAC1, HDAC10, HDAC3, HDAC5
SODIUM PHENYLBUTYRATE	ChEMBL	Phase 4 (approved)	HDAC1, HDAC10, HDAC3, HDAC5
VORINOSTAT	ChEMBL	Phase 4 (approved)	HDAC1, HDAC10, HDAC3, HDAC5
ABEXINOSTAT	ChEMBL	Phase 3	HDAC1, HDAC10, HDAC3, HDAC5
CAFFEIC ACID	ChEMBL	Phase 3	HDAC1, HDAC10, HDAC3, HDAC5
CURCUMIN	ChEMBL	Phase 3	HDAC1, HDAC10, HDAC3, HDAC5
ENTINOSTAT	ChEMBL	Phase 3	HDAC1, HDAC10, HDAC3, HDAC5
TACEDINALINE	ChEMBL	Phase 3	HDAC1, HDAC10, HDAC3, HDAC5
TUCIDINOSTAT	ChEMBL	Phase 3	HDAC1, HDAC10, HDAC3, HDAC5
AR-42	ChEMBL	Phase 2	HDAC1, HDAC10, HDAC3, HDAC5
CHLOROGENIC ACID	ChEMBL	Phase 2	HDAC1, HDAC10, HDAC3, HDAC5
DACINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC10, HDAC3, HDAC5
FIMEPINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC10, HDAC3, HDAC5
NANATINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC10, HDAC3, HDAC5
QUISINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC10, HDAC3, HDAC5
RICOLINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC10, HDAC3, HDAC5
Pazopanib	PubChem	Approved	HDAC1, HDAC10, HDAC3, HDAC5
DOMATINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC10, HDAC3
TINOSTAMUSTINE	ChEMBL	Phase 2	HDAC1, HDAC3, HDAC5
BORTEZOMIB	ChEMBL	Phase 4 (approved)	HDAC1, HDAC3
BUTYRIC ACID	ChEMBL	Phase 2	HDAC1, HDAC3
CITARINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC3
MOCETINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC3
SODIUM BUTYRATE	ChEMBL	Phase 2	HDAC1, HDAC3
.gamma.-aminobutyric acid	PubChem	Approved	HDAC10, HDAC5
acetylcysteine	PubChem	Approved	HDAC10, HDAC5
Gefitinib	PubChem	Approved	HDAC10, HDAC5
ATORVASTATIN	ChEMBL	Phase 4 (approved)	HDAC1
BUFEXAMAC	ChEMBL	Phase 4 (approved)	HDAC10
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	HDAC1
EXIFONE	ChEMBL	Phase 4 (approved)	HDAC1
LOVASTATIN	ChEMBL	Phase 4 (approved)	HDAC1
MOMELOTINIB	ChEMBL	Phase 4 (approved)	HDAC1
VALPROIC ACID	ChEMBL	Phase 4 (approved)	HDAC1
EBSELEN	ChEMBL	Phase 3	HDAC5
BAICALEIN	ChEMBL	Phase 2	HDAC1
MOLIBRESIB	ChEMBL	Phase 2	HDAC1
NICOXAMAT	ChEMBL	Phase 2	HDAC1
RESMINOSTAT	ChEMBL	Phase 2	HDAC1
Crizotinib	PubChem	Approved	HDAC1
Idelalisib	PubChem	Approved	HDAC1