phenylbutanoic acid 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
24 1821-12-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • phenylbutyrate
  • sodium 4-phenylbutanoate
  • sodium 4-phenylbutyrate
  • phenylbutanoic acid
  • buphenyl
  • pheburane
  • benzenebutyric acid
  • 4-Phenylbutanoic acid
  • 4-Phenylbutyric acid
  • gamma-Phenylbutanoic acid
  • sodium phenylbutyrate
  • relyvrio
Approved in combination with taurursodiol, as relyvrio, for the treatment of amyotrophic lateral sclerosis (ALS) in adults.The mechanism by which relyvrio exerts its therapeutic effects in patients with ALS is unknown.
  • Molecular weight: 164.20
  • Formula: C10H12O2
  • CLOGP: 2.28
  • LIPINSKI: 0
  • HAC: 2
  • HDO: 1
  • TPSA: 37.30
  • ALOGS: -2.51
  • ROTB: 4
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
20 g O

ADMET properties:

PropertyValueReference
BA (Bioavailability) 78 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 -0.225 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.315 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 155.239 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 9.506 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 9.210 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 13.330 % High 1
herg hERG pIC50 4.282 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 9.016 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.013 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 8.680 % High 1
kinase-safety-class ACVR2A,ACVR2B,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GSK3B,ITK,JAK1,JAK2,MAP2K6,MAP3K21,MAP3K7,MAPK12,MAPK7,MAPKAPK2,MTOR,NTRK2,PDK1,PDK2,PDK4,PIK3CB,PIK3CG,PIM2,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TGFBR1,TTK,ZAP70 45
kinase-selectivity-class AXL,BRAF,EIF2AK3,EPHB4,GRK2,MAP2K6,STK33 7
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 1.384 High 1
mh-clint Mouse hepatocyte intrinsic clearance 30.974 High 1
mppb Mouse plasma protein binding (% unbound) 42.180 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 0.166 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 12.710 % High 1
rh-clint Rat hepatocyte intrinsic clearance 20.045 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 97.210 % High 1
rppb Rat plasma protein binding (% unbound) 7.360 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 801.678 uM High 1

Approvals:

DateAgencyCompanyOrphan
April 30, 1996 FDA HYPERION THERAPS INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hyperammonaemia 164.41 53.12 25 167 6450 90621805

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hyperammonaemic crisis 55.57 49.24 6 139 57 42621133
Hyperammonaemia 49.61 49.24 10 135 7856 42613334

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hyperammonaemia 148.12 50.44 26 246 13706 110575321
Hyperammonaemic crisis 83.93 50.44 9 263 113 110588914
Ammonia increased 58.50 50.44 11 261 8239 110580788

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC A16AX03 ALIMENTARY TRACT AND METABOLISM
OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS
Various alimentary tract and metabolism products
ATC N07XX19 NERVOUS SYSTEM
OTHER NERVOUS SYSTEM DRUGS
OTHER NERVOUS SYSTEM DRUGS
Other nervous system drugs
MeSH PA D000970 Antineoplastic Agents
CHEBI has role CHEBI:33231 antitubercular agent
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50266 prodrug
CHEBI has role CHEBI:61115 EC 3.5.1.98 (histone deacetylase) inhibitor
CHEBI has role CHEBI:64946 anti-HIV agent
CHEBI has role CHEBI:68495 apoptosis inducer
CHEBI has role CHEBI:63726 neuroprotective agent
CHEBI has role CHEBI:71031 orphan drug
CHEBI has role CHEBI:176497 geroprotector

Related Drugs by ATC class:

A16AX Various alimentary tract and metabolism products 23 drugs
anethole trithionedoxecitinedoxribtimineeliglustatfosdenopteringivosiranglycerol phenylbutyratelonafarniblumasiranmigalastatmiglustatnedosiran show all 23 →
N07XX Other nervous system drugs 23 drugs
amifampridinearimoclomoldeutetrabenazinedextromethorphanedaravoneeplontersenfampridineinotersen laquinimodlevacetylleucineomaveloxolonepatisiran show all 23 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Disorder of the urea cycle metabolism indication 36444000 DOID:9267
Congenital hyperammonemia, type I indication 62522004
Ornithine Carbamyltransferase Deficiency indication 80908008 DOID:9271
Amyotrophic lateral sclerosis indication 86044005 DOID:332
Citrullinemia indication 398680004 DOID:9273
Deficiency of carbamylphosphate synthetase (CPS) indication 765329008 DOID:9280
Hyperammonemia off-label use 9360008
Arginase deficiency off-label use 23501004 DOID:9278
Arginosuccinate Lyase Deficiency off-label use 41013004 DOID:14755
Isovaleryl-CoA dehydrogenase deficiency off-label use 87827003 DOID:14753
Kidney disease contraindication 90708001 DOID:557
Disease of liver contraindication 235856003 DOID:409




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.65 acidic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
3GM/PACKET; 1GM/PACKET RELYVRIO AMYLYX N216660 Sept. 29, 2022 DISCN FOR SUSPENSION ORAL 10251896 Dec. 24, 2033 TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS (ALS) IN ADULTS
3GM/PACKET; 1GM/PACKET RELYVRIO AMYLYX N216660 Sept. 29, 2022 DISCN FOR SUSPENSION ORAL 10857162 Dec. 24, 2033 TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS (ALS) IN ADULTS
3GM/PACKET; 1GM/PACKET RELYVRIO AMYLYX N216660 Sept. 29, 2022 DISCN FOR SUSPENSION ORAL 9872865 Dec. 24, 2033 TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS (ALS) IN ADULTS
0.5GM/PACKET OLPRUVA ACER N214860 Oct. 10, 2025 RX FOR SUSPENSION ORAL 11202767 Oct. 17, 2036 TREATMENT OF A UREA CYCLE DISORDER INVOLVING DEFICIENCIES OF CARBAMYLPHOSPHATE SYNTHETASE, ORNITHINE TRANSCARBAMYLASE, OR ARGININOSUCCINIC ACID SYNTHETASE
1GM/PACKET OLPRUVA ACER N214860 Oct. 10, 2025 RX FOR SUSPENSION ORAL 11202767 Oct. 17, 2036 TREATMENT OF A UREA CYCLE DISORDER INVOLVING DEFICIENCIES OF CARBAMYLPHOSPHATE SYNTHETASE, ORNITHINE TRANSCARBAMYLASE, OR ARGININOSUCCINIC ACID SYNTHETASE
2GM/PACKET OLPRUVA ACER N214860 Dec. 22, 2022 RX FOR SUSPENSION ORAL 11202767 Oct. 17, 2036 TREATMENT OF A UREA CYCLE DISORDER INVOLVING DEFICIENCIES OF CARBAMYLPHOSPHATE SYNTHETASE, ORNITHINE TRANSCARBAMYLASE, OR ARGININOSUCCINIC ACID SYNTHETASE
3GM/PACKET OLPRUVA ACER N214860 Dec. 22, 2022 RX FOR SUSPENSION ORAL 11202767 Oct. 17, 2036 TREATMENT OF A UREA CYCLE DISORDER INVOLVING DEFICIENCIES OF CARBAMYLPHOSPHATE SYNTHETASE, ORNITHINE TRANSCARBAMYLASE, OR ARGININOSUCCINIC ACID SYNTHETASE
4GM/PACKET OLPRUVA ACER N214860 Dec. 22, 2022 RX FOR SUSPENSION ORAL 11202767 Oct. 17, 2036 TREATMENT OF A UREA CYCLE DISORDER INVOLVING DEFICIENCIES OF CARBAMYLPHOSPHATE SYNTHETASE, ORNITHINE TRANSCARBAMYLASE, OR ARGININOSUCCINIC ACID SYNTHETASE
5GM/PACKET OLPRUVA ACER N214860 Dec. 22, 2022 RX FOR SUSPENSION ORAL 11202767 Oct. 17, 2036 TREATMENT OF A UREA CYCLE DISORDER INVOLVING DEFICIENCIES OF CARBAMYLPHOSPHATE SYNTHETASE, ORNITHINE TRANSCARBAMYLASE, OR ARGININOSUCCINIC ACID SYNTHETASE
6.67GM/PACKET OLPRUVA ACER N214860 Dec. 22, 2022 RX FOR SUSPENSION ORAL 11202767 Oct. 17, 2036 TREATMENT OF A UREA CYCLE DISORDER INVOLVING DEFICIENCIES OF CARBAMYLPHOSPHATE SYNTHETASE, ORNITHINE TRANSCARBAMYLASE, OR ARGININOSUCCINIC ACID SYNTHETASE
6GM/PACKET OLPRUVA ACER N214860 Dec. 22, 2022 RX FOR SUSPENSION ORAL 11202767 Oct. 17, 2036 TREATMENT OF A UREA CYCLE DISORDER INVOLVING DEFICIENCIES OF CARBAMYLPHOSPHATE SYNTHETASE, ORNITHINE TRANSCARBAMYLASE, OR ARGININOSUCCINIC ACID SYNTHETASE

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
3GM/PACKET; 1GM/PACKET RELYVRIO AMYLYX N216660 Sept. 29, 2022 DISCN FOR SUSPENSION ORAL Sept. 29, 2027 NEW CHEMICAL ENTITY
3GM/PACKET; 1GM/PACKET RELYVRIO AMYLYX N216660 Sept. 29, 2022 DISCN FOR SUSPENSION ORAL Sept. 29, 2029 TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS (ALS) IN ADULTS

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Aldose reductase Enzyme IC50 4.02 CHEMBL
Histone deacetylase 2 Enzyme IC50 4.19 CHEMBL
Histone deacetylase 1 Enzyme IC50 4.19 CHEMBL
Histone deacetylase 8 Enzyme IC50 4.03 CHEMBL

External reference:

IDSource
D05868 KEGG_DRUG
4346-18-3 SECONDARY_CAS_RN
1716-12-7 SECONDARY_CAS_RN
1545685 RXNORM
CLT PDB_CHEM_ID
CHEMBL1469 ChEMBL_ID
4775 PUBCHEM_CID
CHEMBL1746 ChEMBL_ID
C075773 MESH_SUPPLEMENTAL_RECORD_UI
DB06819 DRUGBANK_ID
C0031465 UMLSCUI
CHEBI:75316 CHEBI
8480 IUPHAR_LIGAND_ID
R9K49A127H UNII
11518 MMSL
205556 MMSL
361870 MMSL
5490 MMSL
66426 MMSL
d04070 MMSL
4021030 VANDF
C000723627 MESH_SUPPLEMENTAL_RECORD_UI
005954 NDDF
005955 NDDF
387058003 SNOMEDCT_US
782572002 SNOMEDCT_US
785624003 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Sodium Phenylbutyrate HUMAN PRESCRIPTION DRUG LABEL 1 49884-006 POWDER 0.94 g ORAL ANDA 21 sections
Sodium Phenylbutyrate HUMAN PRESCRIPTION DRUG LABEL 1 49884-170 TABLET 500 mg ORAL ANDA 12 sections
sodium phenylbutyrate HUMAN PRESCRIPTION DRUG LABEL 1 68462-853 TABLET 500 mg ORAL ANDA 20 sections
Sodium phenylbutyrate HUMAN PRESCRIPTION DRUG LABEL 1 68475-011 TABLET 500 mg ORAL ANDA 19 sections
Sodium phenylbutyrate HUMAN PRESCRIPTION DRUG LABEL 1 70710-2180 TABLET 500 mg ORAL ANDA 19 sections
PHEBURANE HUMAN PRESCRIPTION DRUG LABEL 1 71770-210 PELLET 483 mg ORAL NDA 28 sections
BUPHENYL HUMAN PRESCRIPTION DRUG LABEL 1 75987-060 TABLET 500 mg ORAL NDA 22 sections
Buphenyl HUMAN PRESCRIPTION DRUG LABEL 1 75987-070 POWDER 0.94 g ORAL NDA 22 sections