Phenylbutanoic Acid

Summary

Phenylbutanoic Acid (CHEMBL1469) is an approved small-molecule EC 3.5.1.98 (histone deacetylase) inhibitor; indicated across 7 conditions including hiv infectious disease and brain neoplasm.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Indications: 7 conditions
• Clinical trials: 30
• Chemistry: 164.2 Da · C10H12O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1469
Name	Phenylbutanoic Acid
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	4775
ChEBI	CHEBI:41500
Molecular formula	C10H12O2
Molecular weight	164.2
InChIKey	OBKXEAXTFZPCHS-UHFFFAOYSA-N

SMILES: C1=CC=C(C=C1)CCCC(=O)O

IUPAC name: 4-phenylbutanoic acid

ChEBI definition: A monocarboxylic acid the structure of which is that of butyric acid substituted with a phenyl group at C-4. It is a histone deacetylase inhibitor that displays anticancer activity. It inhibits cell proliferation, invasion and migration and induces apoptosis in glioma cells. It also inhibits protein isoprenylation, depletes plasma glutamine, increases production of foetal haemoglobin through transcriptional activation of the γ-globin gene and affects hPPARγ activation.

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

Also known as: Phenylbutanoic acid, Phenyl butyric acid, SID855904, Phenylbutyric acid, clt, SID67217, PHENYLBUTYRIC ACID, PHENYLBUTANOIC ACID, Phenylbutyrate, Phenylbutyric_acid sodium salt, C0164531, PHENYLBUTYRATE

Parent form; salt/anhydrous children: CHEMBL1746

Patent coverage: 11,845 distinct patent families (37,081 SureChEMBL compound mentions), from 1 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

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Survival motor neuron protein, Histone deacetylase 2, Histone deacetylase, Alpha-1A adrenergic receptor, Sodium-dependent dopamine transporter, Histone deacetylase 8, Histone deacetylase 1, Mitogen-activated protein kinase 1.

Bioactivity

ChEMBL activities: 3 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
SMN1	5.95	Potency	1122	nM	CHEMBL_ACT_3866268
HDAC3	5.55	Ki	2800	nM	CHEMBL_ACT_2998026
SLC6A3	5.5	AC50	3200	nM	CHEMBL_ACT_25124053

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

7 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
HIV infectious disease	2	MONDO:0005109	EFO:0000764
brain neoplasm	2	MONDO:0021211	EFO:0003833
pulmonary tuberculosis	2	MONDO:0006052	EFO:1000049
maple syrup urine disease	2	MONDO:0009563	MONDO:0009563
beta thalassemia	2	MONDO:0019402	MONDO:0016486
neuroblastoma	1	MONDO:0005072	EFO:0000621
inclusion body myositis	1	MONDO:0007827	EFO:0007323

Clinical trials

Total trials: 30.

Phase distribution

Phase	Trials
PHASE2	11
PHASE1	8
PHASE1/PHASE2	5
Not specified	3
PHASE4	1
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00533559	PHASE4	COMPLETED	Mechanism of Fatty Acid-induced Impairment of Glucose-simulated Insulin Secretion - Effect of Buphenyl
NCT01529060	PHASE2/PHASE3	COMPLETED	Phenylbutyrate Therapy for Maple Syrup Urine Disease
NCT06773026	PHASE2	RECRUITING	Study of Sodium Phenylbutyrate (ACER-001) for the Treatment of Pediatric and Adults Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
NCT00002796	PHASE1/PHASE2	TERMINATED	Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate in Advanced Colorectal Cancer
NCT00004767	PHASE2	COMPLETED	Phase II Study of Sodium Phenylbutyrate, Sodium Benzoate, Sodium Phenylacetate, and Dietary Intervention for Urea Cycle Disorders
NCT00006019	PHASE2	COMPLETED	Phenylbutyrate Plus Azacitidine in Treating Patients With Acute Myeloid Leukemia, Myelodysplasia, Non-Hodgkin’s Lymphoma, Multiple Myeloma, Non-small Cell Lung Cancer, or Prostate Cancer
NCT00006240	PHASE2	COMPLETED	Phenylbutyrate, Dexamethasone, and Sargramostim in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia
NCT00006450	PHASE2	COMPLETED	Phenylbutyrate to Treat Children With Progressive or Recurrent Brain Tumors
NCT00107770	PHASE1/PHASE2	COMPLETED	Safety Study of Oral Sodium Phenylbutyrate in Subjects With ALS (Amyotrophic Lateral Sclerosis)
NCT00212316	PHASE2	COMPLETED	Safety and Tolerability Study of Phenylbutyrate in Huntington’s Disease (PHEND-HD)
NCT00345605	PHASE2	COMPLETED	Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder
NCT00387530	PHASE2	WITHDRAWN	Phenylbutyrate and Valganciclovir in Treating Patients With Relapsed or Refractory Epstein-Barr Virus-Positive Cancer
NCT00439218	PHASE1/PHASE2	TERMINATED	Clinical Trial of Sodium Phenylbutyrate in Children With Spinal Muscular Atrophy Type I
NCT00439569	PHASE1/PHASE2	TERMINATED	Clinical Trial of Sodium Phenylbutyrate in Children With Spinal Muscular Atrophy Types II or III
NCT00528268	PHASE1/PHASE2	COMPLETED	Study to Evaluate Sodium Phenylbutyrate in Pre-symptomatic Infants With Spinal Muscular Atrophy
NCT01096095	PHASE2	WITHDRAWN	Pilot Study of Safety and Efficacy of Sodium Phenylbutyrate in Spinocerebellar Ataxia Type 3
NCT03734263	PHASE2	COMPLETED	Use of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency.
NCT06069375	PHASE2	SUSPENDED	Study of Sodium Phenylbutyrate (ACER-001) for the Treatment of Patients With Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
NCT07125066	PHASE1	ENROLLING_BY_INVITATION	An Individual Patient, Open Label Study to Use ACER-001 to Treat Combined D,L-2 Hydroxyglutaric Aciduria (C-2HGA)
NCT00001565	PHASE1	COMPLETED	Phase I and Pharmacokinetic Trial of Phenylbutyrate Given as a Continuous Infusion in Pediatric Patients With Refractory Malignancy
NCT00002909	PHASE1	COMPLETED	Phenylbutyrate in Treating Patients With Refractory Solid Tumors or Lymphoma
NCT00004871	PHASE1	COMPLETED	Azacitidine Plus Phenylbutyrate in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
NCT00005639	PHASE1	COMPLETED	Azacitidine Plus Phenylbutyrate in Treating Patients With Advanced or Metastatic Solid Tumors That Have Not Responded to Previous Treatment
NCT00006239	PHASE1	COMPLETED	Phenylbutyrate and Tretinoin in Treating Patients With Hematologic Cancer
NCT04421677	PHASE1	COMPLETED	Safety and Tolerability of Phenylbutyrate in Inclusion Body Myositis
NCT05349435	PHASE1	TERMINATED	A Healthy Volunteer Study to Compare Fezagepras (PBI-4050) With Sodium Phenylbutyrate
NCT06645769	EARLY_PHASE1	NOT_YET_RECRUITING	Na-Phenylbutyrate VAscular Trial
NCT00771901	Not specified	COMPLETED	Effect of Endoplasmic Reticulum Stress on Metabolic Function
NCT02111200	Not specified	COMPLETED	Comparative Efficacy of Phenylbutyrate (PBA) vs. Benzoate in Urea Cycle Disorders
NCT05028803	Not specified	COMPLETED	The Effects of Sodium Phenylbutyrate on Circulating Branched Chain Amino Acids

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).