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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:10
Primary Accession Number DB00313
Secondary Accession Number
  • APRD00256
Name Valproic Acid
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage dependent sodium channels. [PubChem]
Synonyms
  1. DPA
  2. Di-n-propylacetic acid
  3. Di-n-propylessigsaure
  4. Dipropylacetic acid
  5. Kyselina 2-propylvalerova
  6. Myproic Acid
  7. Propylvaleric acid
  8. Sodium hydrogen divalproate
  9. Valproate semisodique [French]
  10. Valproate semisodium
  11. Valproato semisodico [Spanish]
  12. Valproatum seminatricum [Latin]
  13. n-DPA
  14. n-Dipropylacetic acid
Brand Names
  1. Alti-Valproic
  2. Avugane
  3. Baceca
  4. Convulex
  5. Delepsine
  6. Depakene
  7. Depakine
  8. Deproic
  9. Dom-Valproic
  10. Epilex
  11. Epilim
  12. Epival
  13. Ergenyl
  14. Med Valproic
  15. Mylproin
  16. Novo-Valproic
  17. Nu-Valproic
  18. PMS-Valproic Acid
  19. Penta-Valproic
  20. Sprinkle
  21. Valcote
  22. Valparin
  23. Valproic acid USP
  24. Valproic acid USP24
Brand Mixtures Not Available
Chemical IUPAC Name 2-propylpentanoic acid
Chemical Formula C8H16O2
Chemical Structure Structure
CAS Registry Number 99-66-1
InChI Identifier InChI=1/C8H16O2/c1-3-5-7(6-4-2)8(9)10/h7H,3-6H2,1-2H3,(H,9,10)/f/h9H
InChI Key NIJJYAXOARWZEE-BGGKNDAXCP
KEGG Drug D00399 Link Image
KEGG Compound Not Available
PubChem Compound 3121 Link Image
PubChem Substance 7854737 Link Image
ChEBI ID 9926 Link Image
PharmGKB ID PA451846 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02260654 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/depakene.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/dep1124.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Valproic_Acid Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Oberreit, Ber.29, 1998 (1896)
Average Molecular Weight 144.2114
Monoisotopic Molecular Weight 144.1150
State Solid
Melting Point 120 - 130 oC
Experimental Water Solubility Slightly soluble (1.3 mg/mL) Source: PhysProp
Predicted Water Solubility 2.36e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 2.7 Source: PhysProp
Predicted LogP 2.54 Calculated using ALOGPS
Experimental LogS -1.86 [ADME Research, USCD]
Predicted LogS -1.79 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 4.8
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID 1OHY Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES CCCC(CCC)C(O)=O
Canonical SMILES CCCC(CCC)C(O)=O
Drug Category
  • Anticonvulsants
  • Antimanic Agents
  • Enzyme Inhibitors
  • GABA Agents
ATC Codes
AHFS Codes
  • 28:12.92
Indication For use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types which include absence seizures.
Pharmacology Valproic Acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat migraine headaches and schizophrenia. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, and the seizures associated with Lennox-Gastaut syndrome. Valproic Acid is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain. Valproic Acid dissociates to the valproate ion in the gastrointestinal tract. Valproic acid has also been shown to be an inhibitor of an enzyme called histone deacetylase 1 (HDAC1). HDAC1 is needed for HIV to remain in infected cells. A study published in August 2005 revealed that patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a 75% reduction in latent HIV infection.
Mechanism of Action Valproic Acid binds to and inhibits GABA transaminase. The drug's anticonvulsant activity may be related to increased brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. Valproic Acid may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels.
Absorption Rapid absorption from gastrointestinal tract.
Toxicity Oral, mouse: LD50 = 1098 mg/kg; Oral, rat: LD50 = 670 mg/kg. Symptoms of overdose may include coma, extreme drowsiness, and heart problems.
Protein Binding The plasma protein binding of valproate is concentration dependent and the free fraction increases from approximately 10% at 40 µg/mL to 18.5% at 130 µg/mL.
Biotransformation Valproic Acid is metabolized almost entirely by the liver. In adult patients on monotherapy, 30-50% of an administered dose appears in urine as a glucuronide conjugate. Mitochondrial ß-oxidation is the other major metabolic pathway, typically accounting for over 40% of the dose. Usually, less than 15-20% of the dose is eliminated by other oxidative mechanisms. Less than 3% of an administered dose is excreted unchanged in urine.
Half Life 9-16 hours
Dosage Forms
Form Route
Capsule Oral
Capsule, coated Oral
Liquid Intravenous
Syrup Oral
Tablet, coated Oral
Tablet, delayed release Oral
Tablet, extended release Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Clarithromycin The macrolide antibiotic, Erythromycin, may increase the serum concentratin of Valproic acid. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Clarithromycin is initiated, discontinued or dose changed.
Erythromycin The macrolide antibiotic, Erythromycin, may increase the serum concentratin of Valproic acid. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Erythromycin is initiated, discontinued or dose changed.
Felbamate Felbamate, a CYP2C19 inhibitor, may decrease the metabolism of Valproic acid, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Felbamate is initiated, discontinued or dose changed.
Lamotrigine Valproic acid may increase the adverse effects of Lamotrigine by increasing Lamotrigine serum concentration. The Lamotrigine dose should be reduced by 50% during concomitant therapy. Monitor for changes in Lamotrigine therapeutic and adverse effects if Valproic acid is initiated, discontinued or dose changed.
Lorazepam Valproic acid may increase the serum concentration of Lorazepam by reducing Lorazepam metabolism. The Lorazepam dose should be reduced by 50% during concomitant therapy. Monitor for increased Lorazepam effects and toxicity.
Rifampin Rifampin may reduce the serum concentration of Valproic acid by increasing Valproic acid metabolism. Valproic acid dose adjustments may be required during concomitant therapy. Monitor Valproic acid serum concentrations, efficacy and toxicity if Rifampin is initiated, discontinued or dose changed.
Telithromycin The macrolide antibiotic, Erythromycin, may increase the serum concentratin of Valproic acid. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Telithromycin is initiated, discontinued or dose changed.
rufinamide Valproic acid may increase the therapeutic/toxic effects of Rufinamide. Consider alternate therapy or monitor for changes in Rufinamide serum concentrations, therapeutic and adverse effects if Valproic acid is initiated, discontinued or dose changed.
Food Interactions
  • Avoid alcohol.
  • Do not take with milk.
  • Take with food.
Pathways Not Available
General References
  1. Lehrman G, Hogue IB, Palmer S, Jennings C, Spina CA, Wiegand A, Landay AL, Coombs RW, Richman DD, Mellors JW, Coffin JM, Bosch RJ, Margolis DM: Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet. 2005 Aug 13-19;366(9485):549-55. [PubMed Link Image]
  2. Valentini A, Gravina P, Federici G, Bernardini S: Valproic acid induces apoptosis, p16INK4A upregulation and sensitization to chemotherapy in human melanoma cells. Cancer Biol Ther. 2007 Feb;6(2):185-91. Epub 2007 Feb 5. [PubMed Link Image]
  3. Schwartz C, Palissot V, Aouali N, Wack S, Brons NH, Leners B, Bosseler M, Berchem G: Valproic acid induces non-apoptotic cell death mechanisms in multiple myeloma cell lines. Int J Oncol. 2007 Mar;30(3):573-82. [PubMed Link Image]
  4. Rosenberg G: The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? Cell Mol Life Sci. 2007 Aug;64(16):2090-103. [PubMed Link Image]
  5. Drugs.com Link Image
  6. Wikipedia Link Image
  7. RxList Link Image
  8. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. 4-aminobutyrate aminotransferase, mitochondrial
  2. Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial
  3. Histone deacetylase 9
Drug Target 1 [top]
Target 1 ID 280
Target 1 Name 4-aminobutyrate aminotransferase, mitochondrial
Target 1 Synonyms
  1. (S)-3-amino-2-methylpropionate transaminase
  2. 4-aminobutyrate aminotransferase, mitochondrial precursor
  3. EC 2.6.1.19
  4. EC 2.6.1.22
  5. GABA aminotransferase
  6. GABA transaminase
  7. GABA-AT
  8. GABA-T
  9. Gamma-amino-N-butyrate transaminase
  10. L-AIBAT
Target 1 Gene Name ABAT
Target 1 Protein Sequence >4-aminobutyrate aminotransferase, mitochondrial precursor 
MASMLLAQRLACSFQHSYRLLVPGSRHISQAAAKVDVEFDYDGPLMKTEVPGPRSQELMK
QLNIIQNAEAVHFFCNYEESRGNYLVDVDGNRMLDLYSQISSVPIGYSHPALLKLIQQPQ
NASMFVNRPALGILPPENFVEKLRQSLLSVAPKGMSQLITMACGSCSNENALKTIFMWYR
SKERGQRGFSQEELETCMINQAPGCPDYSILSFMGAFHGRTMGCLATTHSKAIHKIDIPS
FDWPIAPFPRLKYPLEEFVKENQQEEARCLEEVEDLIVKYRKKKKTVAGIIVEPIQSEGG
DNHASDDFFRKLRDIARKHGCAFLVDEVQTGGGCTGKFWAHEHWGLDDPADVMTFSKKMM
TGGFFHKEEFRPNAPYRIFNTWLGDPSKNLLLAEVINIIKREDLLNNAAHAGKALLTGLL
DLQARYPQFISRVRGRGTFCSFDTPDDSIRNKLILIARNKGVVLGGCGDKSIRFRPTLVF
RDHHAHLFLNIFSDILADFK
Target 1 Number of Residues 508
Target 1 Molecular Weight 56440
Target 1 Theoretical pI 8.04
Target 1 GO Classification
Function
4-aminobutyrate transaminase activity
binding
vitamin binding
pyridoxal phosphate binding
catalytic activity
transferase activity
transferase activity, transferring nitrogenous groups
transaminase activity
Process
physiological process
metabolism
cellular metabolism
amino acid and derivative metabolism
amino acid derivative metabolism
gamma-aminobutyric acid metabolism
Component
Not Available
Target 1 General Function Amino acid transport and metabolism
Target 1 Specific Function Catalyzes the conversion of gamma-aminobutyrate and L- beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate and beta-alanine
Target 1 Pathways
Name SMPDB Link KEGG Link
Valine, leucine and isoleucine degradation SMP00032 Link Image map00280 Link Image
Target 1 Reactions
  • 4-aminobutanoate + 2-oxoglutarate = succinate semialdehyde + L-glutamate
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 602705 Link Image
Target 1 UniProtKB/Swiss-Prot ID P80404 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name GABT_HUMAN Link Image
Target 1 PDB ID 1OHY Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Mitochondrion
  • mitochondrial matrix
Target 1 Gene Sequence >1503 bp 
ATGGCCTCCATGTTGCTCGCCCAGCGGCTGGCCTGCAGCTTCCAGCACACGTACCGCCTG
CTGGTGCCTGGATCCAGACACATTAGTCAAGCTGCAGCCAAAGTCGACGTTGAATTTGAT
TATGATGGGCCTCTGATGAAGACGGAAGTCCCAGGGCCTAGATCTCAGGAGTTAATGAAA
CAGCTGAATATAATTCAGAATGCAGAGGCTGTGCATTTTTTCTGCAATTACGAAGAGAGC
CGAGGCAATTACCTGGTTGATGTGGACGGCAACCGAATGCTGGATCTTTATTCCCAGATC
TCCTCTGTTCCCATAGGTTACAGCGACCCGGCCCTCGTGAAACTCATCCAACAGCCACAA
AATGCGAGCATGTTTGTCAACAGACCCGCCCTCGAAATCCTGCCTCCGGAGAACTTTGTG
GAGAAGCTCCGGCAGTCCTTGCTCTCGGTGGCTCCCAAAGGGATGTCCCAGCTCATCACC
ATGGCCTGCGGCTCCTGCTCCAATGAAAACGCCTTAAAGACCATCTTCATGTGGTACCGG
AGCAAGGAAAGAGGGCAGAGGGGATTCTCCAAAGAGGAGCTGGAGACGTGCATGATTAAC
CAGGCCCCCTGGTGCCCCGACTACAGCATCCTCTCCTTCATGGGTTCCTTCCATGGGAGG
ACCATGGGTTGCTTAGCGACCACGCACTCTAAAGCCATTCACAAGATCGATATCCCTTCC
TTTGACTGGCCCATCGCACCGTTCCCACGGCTGAAATACCCTCTGGAAGAGTTTGTGAAA
GAGAACCAACAGGAAGAGGCCGGCTGTCTGGAAGAGGTTGAGGATCTGATTGTGAAATAT
CGAAAAAAGAAGAAGACGGTGGCCGGGATCATCGTGGAGCCCATCCAGTCCGAGGGTGGA
GACAACCATGCATCCGATGACTTCTTTCGGAAGCTGAGAGACATCGCCAGGAAGCACTGC
TGCGCCTTCTTGGTGGACGAGGTCCAGACCGGAGGAGGCTGCACGGGCAAGTTCTGGGCC
CATGAGCACTGGGGCCTGGATGACCCAGCAGACGTGATGACCTTCAGCAAGAAGATGATG
ACTGGGGGCTTCTTCCTCAAGGAGGAGTTCAGGCCTAATGCTCCCTACCGGATCTTCAAC
ACGTGGCTGGGGGACCCGTCCAAGAACCTGTTGCTGGCTGAGGTCATCAACATCATCAAG
CGGGAGGACCTGCTAAATAATGCAGCCCATGCCGGGAAGGCCCTGCTCACAGGACTGCTG
GACCTCCAGGCCCGGTACCCCCAGTTCATCAGCAGGGTGAGAGGACGAGGCACCTTTTGC
TCCTTCGATACTCCCGATGATTCCATACGGAATAAGCTCATTTTAATTGCCAGAAACAAA
GGTGTGGTGTTGGGTGGCTGTGGTGACAAATCCATTCGTTTCCGTCCCACGCTGGTGTTC
AGGGATCACCACGCTCACCTGTTCCTCAATATTTTCAGTGACATCTTAGCAGACTTCAAG
TAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID ABAT Link Image
Target 1 GenAtlas ID ABAT Link Image
Target 1 HGNC ID HGNC:23 Link Image
Target 1 Chromosome Location 16
Target 1 Locus 16p13.2
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Medina-Kauwe LK, Tobin AJ, De Meirleir L, Jaeken J, Jakobs C, Nyhan WL, Gibson KM: 4-Aminobutyrate aminotransferase (GABA-transaminase) deficiency. J Inherit Metab Dis. 1999 Jun;22(4):414-27. [PubMed Link Image]
  2. Osei YD, Churchich JE: Screening and sequence determination of a cDNA encoding the human brain 4-aminobutyrate aminotransferase. Gene. 1995 Apr 3;155(2):185-7. [PubMed Link Image]
  3. De Biase D, Barra D, Simmaco M, John RA, Bossa F: Primary structure and tissue distribution of human 4-aminobutyrate aminotransferase. Eur J Biochem. 1995 Jan 15;227(1-2):476-80. [PubMed Link Image]
Target 1 Drug References
  1. Ha JH, Lee DU, Lee JT, Kim JS, Yong CS, Kim JA, Ha JS, Huh K: 4-Hydroxybenzaldehyde from Gastrodia elata B1. is active in the antioxidation and GABAergic neuromodulation of the rat brain. J Ethnopharmacol. 2000 Nov;73(1-2):329-33. [PubMed Link Image]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  3. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
  4. Semba J, Kuroda Y, Takahashi R: Potential antidepressant properties of subchronic GABA transaminase inhibitors in the forced swimming test in mice. Neuropsychobiology. 1989;21(3):152-6. [PubMed Link Image]
  5. Loscher W: Anticonvulsant and biochemical effects of inhibitors of GABA aminotransferase and valproic acid during subchronic treatment in mice. Biochem Pharmacol. 1982 Mar 1;31(5):837-42. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 630
Target 2 Name Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial
Target 2 Synonyms
  1. 2-MEBCAD
  2. 2-methyl branched chain acyl-CoA dehydrogenase
  3. 2-methylbutyryl-CoA dehydrogenase
  4. 2-methylbutyryl-coenzyme A dehydrogenase
  5. EC 1.3.99.-
  6. SBCAD
  7. Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial precursor
Target 2 Gene Name ACADSB
Target 2 Protein Sequence >Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial precursor 
MEGLAVRLLRGSRLLRRNFLTCLSSWKIPPHVSKSSQSEALLNITNNGIHFAPLQTFTDE
EMMIKSSVKKFAQEQIAPLVSTMDENSKMEKSVIQGLFQQGLMGIEVDPEYGGTGASFLS
TVLVIEELAKVDASVAVFCEIQNTLINTLIRKHGTEEQKATYLPQLTTEKVGSFCLSEAG
AGSDSFALKTRADKEGDYYVLNGSKMWISSAEHAGLFLVMANVDPTIGYKGITSFLVDRD
TPGLHIGKPENKLGLRASSTCPLTFENVKVPEANILGQIGHGYKYAIGSLNEGRIGIAAQ
MLGLAQGCFDYTIPYIKERIQFGKRLFDFQGLQHQVAHVATQLEAARLLTYNAARLLEAG
KPFIKEASMAKYYASEIAGQTTSKCIEWMGGVGYTKDYPVEKYFRDAKIGTIYEGASNIQ
LNTIAKHIDAEY
Target 2 Number of Residues 439
Target 2 Molecular Weight 47486
Target 2 Theoretical pI 7.00
Target 2 GO Classification
Function
catalytic activity
oxidoreductase activity
oxidoreductase activity, acting on the CH-CH group of donors
acyl-CoA dehydrogenase activity
Process
physiological process
metabolism
cellular metabolism
generation of precursor metabolites and energy
electron transport
Component
Not Available
Target 2 General Function Lipid transport and metabolism
Target 2 Specific Function Has greatest activity toward short branched chain acyl- CoA derivative such as (s)-2-methylbutyryl-CoA, isobutyryl-CoA, and 2-methylhexanoyl-CoA as well as toward short straight chain acyl-CoAs such as butyryl-CoA and hexanoyl-CoA. Can use valproyl- CoA as substrate and may play a role in controlling the metabolic flux of valproic acid in the development of toxicity of this agent
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 531391 Link Image
Target 2 UniProtKB/Swiss-Prot ID P45954 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name ACDSB_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Mitochondrion
  • mitochondrial matrix
Target 2 Gene Sequence >1299 bp 
ATGGAGGGCCTGGCAGTGCGGTTGCTGCGCGGCAGCAGGCTGCTAAGAAGAAATTTCCTG
ACTTGTTTGTCTTCTTGGAAGATTCCTCCTCATGTCTCAAAATCTTCCCAGTCAGAAGCT
CTACTCAATATAACAAATAATGGAATACACTTTGCTCCCCTGCAAACATTTACAGATGAG
GAAATGATGATAAAGAGTTCAGTTAAAAAATTTGCTCAGGAACAAATTGCACCTTTGGTT
TCAACCATGGATGAAAATTCGAAAATGGAGAAATCAGTAATACAAGGATTATTTCAACAA
GGGTTGATGGGTATTGAAGTTGACCCAGAATATGGAGGCACAGGAGCTTCTTTTTTATCC
ACTGTGCTCGTGATAGAGGAATTAGCCAAAGTTGATGCATCTGTGGCTGTCTTTTGTGAG
ATCCAGAACACATTAATTAACACACTGATTAGAAAACATGGAACAGAAGAACAAAAGGCC
ACCTATTTGCCTCAGCTCACTACAGAAAAAGTAGGAAGTTTCTGCCTTTCAGAGGCTGGA
GCAGGTAGTGACTCATTTGCTTTGAAGACCAGAGCTGATAAAGAGGGAGATTATTATGTC
CTCAATGGATCAAAGATGTGGATCAGCAGTGCTGAGCATGCAGGGCTCTTTCTGGTGATG
GCAAATGTAGACCCTACCATTGGATATAAGGGAATTACCTCCTTCTTAGTAGATCGTGAT
ACTCCGGGCCTTCATATAGGGAAACCTGAAAACAAATTGGGGCTCAGAGCTTCTTCCACC
TGCCCGTTAACATTCGAAAATGTCAAGGTTCCAGAAGCCAATATCTTGGGACAAATTGGA
CATGGCTATAAGTATGCCATAGGGAGTCTCAATGAAGGTAGAATAGGAATTGCTGCACAG
ATGCTGGGACTGGCGCAAGGATGTTTTGACTACACTATTCCATATATTAAAGAAAGGATA
CAATTTGGCAAAAGACTATTTGATTTTCAGGGCCTCCAACACCAAGTGGCTCACGTGGCC
ACCCAGCTGGAAGCTGCAAGATTACTAACATACAATGCTGCTAGGCTTTTAGAAGCTGGA
AAGCCATTCATAAAAGAAGCGTCAATGGCCAAATACTATGCATCAGAGATTGCAGGACAA
ACAACGAGTAAATGTATCGAGTGGATGGGGGGAGTAGGCTACACCAAAGATTACCCTGTG
GAGAAATACTTCCGAGATGCAAAGATTGGTACGATATATGAAGGAGCTTCCAACATCCAG
TTGAACACCATTGCAAAGCATATCGATGCAGAATACTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID ACADSB Link Image
Target 2 GenAtlas ID ACADSB Link Image
Target 2 HGNC ID HGNC:91 Link Image
Target 2 Chromosome Location 10
Target 2 Locus 10q26.13
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Gibson KM, Burlingame TG, Hogema B, Jakobs C, Schutgens RB, Millington D, Roe CR, Roe DS, Sweetman L, Steiner RD, Linck L, Pohowalla P, Sacks M, Kiss D, Rinaldo P, Vockley J: 2-Methylbutyryl-coenzyme A dehydrogenase deficiency: a new inborn error of L-isoleucine metabolism. Pediatr Res. 2000 Jun;47(6):830-3. [PubMed Link Image]
  2. Andresen BS, Christensen E, Corydon TJ, Bross P, Pilgaard B, Wanders RJ, Ruiter JP, Simonsen H, Winter V, Knudsen I, Schroeder LD, Gregersen N, Skovby F: Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase deficiency: identification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in isoleucine and valine metabolism. Am J Hum Genet. 2000 Nov;67(5):1095-103. Epub 2000 Sep 29. [PubMed Link Image]
  3. Rozen R, Vockley J, Zhou L, Milos R, Willard J, Fu K, Vicanek C, Low-Nang L, Torban E, Fournier B: Isolation and expression of a cDNA encoding the precursor for a novel member (ACADSB) of the acyl-CoA dehydrogenase gene family. Genomics. 1994 Nov 15;24(2):280-7. [PubMed Link Image]
Target 2 Drug References
  1. Ito M, Ikeda Y, Arnez JG, Finocchiaro G, Tanaka K: The enzymatic basis for the metabolism and inhibitory effects of valproic acid: dehydrogenation of valproyl-CoA by 2-methyl-branched-chain acyl-CoA dehydrogenase. Biochim Biophys Acta. 1990 May 16;1034(2):213-8. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 1039
Target 3 Name Histone deacetylase 9
Target 3 Synonyms
  1. HD7
  2. HD7B
  3. HD9
  4. Histone deacetylase-related protein
  5. MEF2-interacting transcription repressor MITR
Target 3 Gene Name HDAC9
Target 3 Protein Sequence >Histone deacetylase 9 
MHSMISSVDVKSEVPVGLEPISPLDLRTDLRMMMPVVDPVVREKQLQQELLLIQQQQQIQ
KQLLIAEFQKQHENLTRQHQAQLQEHIKELLAIKQQQELLEKEQKLEQQRQEQEVERHRR
EQQLPPLRGKDRGRERAVASTEVKQKLQEFLLSKSATKDTPTNGKNHSVSRHPKLWYTAA
HHTSLDQSSPPLSGTSPSYKYTLPGAQDAKDDFPLRKTASEPNLKVRSRLKQKVAERRSS
PLLRRKDGNVVTSFKKRMFEVTESSVSSSSPGSGPSSPNNGPTGSVTENETSVLPPTPHA
EQMVSQQRILIHEDSMNLLSLYTSPSLPNITLGLPAVPSQLNASNSLKEKQKCETQTLRQ
GVPLPGQYGGSIPASSSHPHVTLEGKPPNSSHQALLQHLLLKEQMRQQKLLVAGGVPLHP
QSPLATKERISPGIRGTHKLPRHRPLNRTQSAPLPQSTLAQLVIQQQHQQFLEKQKQYQQ
QIHMNKLLSKSIEQLKQPGSHLEEAEEELQGDQAMQEDRAPSSGNSTRSDSSACVDDTLG
QVGAVKVKEEPVDSDEDAQIQEMESGEQAAFMQQPFLEPTHTRALSVRQAPLAAVGMDGL
EKHRLVSRTHSSPAASVLPHPAMDRPLQPGSATGIAYDPLMLKHQCVCGNSTTHPEHAGR
IQSIWSRLQETGLLNKCERIQGRKASLEEIQLVHSEHHSLLYGTNPLDGQKLDPRILLGD
DSQKFFSSLPCGGLGVDSDTIWNELHSSGAARMAVGCVIELASKVASGELKNGFAVVRPP
GHHAEESTAMGFCFFNSVAITAKYLRDQLNISKILIVDLDVHHGNGTQQAFYADPSILYI
SLHRYDEGNFFPGSGAPNEVGTGLGEGYNINIAWTGGLDPPMGDVEYLEAFRTIVKPVAK
EFDPDMVLVSAGFDALEGHTPPLGGYKVTAKCFGHLTKQLMTLADGRVVLALEGGHDLTA
ICDASEACVNALLGNELEPLAEDILHQSPNMNAVISLQKIIEIQSMSLKFS
Target 3 Number of Residues 1027
Target 3 Molecular Weight 111298
Target 3 Theoretical pI 6.88
Target 3 GO Classification Not Available
Target 3 General Function Involved in histone deacetylase activity
Target 3 Specific Function Isoform 3, called MITR/HDRP, lacks active site residues and therefore is catalytically inactive. Represses MEF2-dependent transcription by recruiting HDAC1 and/or HDAC3. Seems to inhibit skeletal myogenesis and to be involved in heart development. Protects neurons from apoptosis, both by inhibiting c-Jun phosphorylation by MAPK10 and by repressing c-Jun transcription via HDAC1 recruitment to c-Jun promoter
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 15590680 Link Image
Target 3 UniProtKB/Swiss-Prot ID Q9UKV0 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name HDAC9_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location Not Available
Target 3 Gene Sequence >3036 bp 
ATGCACAGTATGATCAGCTCAGTGGATGTGAAGTCAGAAGTTCCTGTGGGCCTGGAGCCC
ATCTCACCTTTAGACCTAAGGACAGACCTCAGGATGATGATGCCCGTGGTGGACCCTGTT
GTCCGTGAGAAGCAATTGCAGCAGGAATTACTTCTTATCCAGCAGCAGCAACAAATCCAG
AAGCAGCTTCTGATAGCAGAGTTTCAGAAACAGCATGAGAACTTGACACGGCAGCACCAG
GCTCAGCTTCAGGAGCATATCAAGGAACTTCTAGCCATAAAACAGCAACAAGAACTCCTA
GAAAAGGAGCAGAAACTGGAGCAGCAGAGGCAAGAACAGGAAGTAGAGAGGCATCGCAGA
GAACAGCAGCTTCCTCCTCTCAGAGGCAAAGATAGAGGACGAGAAAGGGCAGTGGCAAGT
ACAGAAGTAAAGCAGAAGCTTCAAGAGTTCCTACTGAGTAAATCAGCAACGAAAGACACT
CCAACTAATGGAAAAAATCATTCCGTGAGCCGCCATCCCAAGCTCTGGTACACGGCTGCC
CACCACACATCATTGGATCAAAGCTCTCCACCCCTTAGTGGAACATCTCCATCCTACAAG
TACACATTACCAGGAGCACAAGATGCAAAGGATGATTTCCCCCTTCGAAAAACTGCCTCT
GAGCCCAACTTGAAGGTGCGGTCCAGGTTAAAACAGAAAGTGGCAGAGAGGAGAAGCAGC
CCCTTACTCAGGCGGAAGGATGGAAATGTTGTCACTTCATTCAAGAAGCGAATGTTTGAG
GTGACAGAATCCTCAGTCAGTAGCAGTTCTCCAGGCTCTGGTCCCAGTTCACCAAACAAT
GGGCCAACTGGAAGTGTTACTGAAAATGAGACTTCGGTTTTGCCCCCTACCCCTCATGCC
GAGCAAATGGTTTCACAGCAACGCATTCTAATTCATGAAGATTCCATGAACCTGCTAAGT
CTTTATACCTCTCCTTCTTTGCCCAACATTACCTTGGGGCTTCCCGCAGTGCCATCCCAG
CTCAATGCTTCGAATTCACTCAAAGAAAAGCAGAAGTGTGAGACGCAGACGCTTAGGCAA
GGTGTTCCTCTGCCTGGGCAGTATGGAGGCAGCATCCCGGCATCTTCCAGCCACCCTCAT
GTTACTTTAGAGGGAAAGCCACCCAACAGCAGCCACCAGGCTCTCCTGCAGCATTTATTA
TTGAAAGAACAAATGCGACAGCAAAAGCTTCTTGTAGCTGGTGGAGTTCCCTTACATCCT
CAGTCTCCCTTGGCAACAAAAGAGAGAATTTCACCTGGCATTAGAGGTACCCACAAATTG
CCCCGTCACAGACCCCTGAACCGAACCCAGTCTGCACCTTTGCCTCAGAGCACGTTGGCT
CAGCTGGTCATTCAACAGCAACACCAGCAATTCTTGGAGAAGCAGAAGCAATACCAGCAG
CAGATCCACATGAACAAACTGCTTTCGAAATCTATTGAACAACTGAAGCAACCAGGCAGT
CACCTTGAGGAAGCAGAGGAAGAGCTTCAGGGGGACCAGGCGATGCAGGAAGACAGAGCG
CCCTCTAGTGGCAACAGCACTAGGAGCGACAGCAGTGCTTGTGTGGATGACACACTGGGA
CAAGTTGGGGCTGTGAAGGTCAAGGAGGAACCAGTGGACAGTGATGAAGATGCTCAGATC
CAGGAAATGGAATCTGGGGAGCAGGCTGCTTTTATGCAACAGCCTTTCCTGGAACCCACG
CACACACGTGCGCTCTCTGTGCGCCAAGCTCCGCTGGCTGCGGTTGGCATGGATGGATTA
GAGAAACACCGTCTCGTCTCCAGGACTCACTCTTCCCCTGCTGCCTCTGTTTTACCTCAC
CCAGCAATGGACCGCCCCCTCCAGCCTGGCTCTGCAACTGGAATTGCCTATGACCCCTTG
ATGCTGAAACACCAGTGCGTTTGTGGCAATTCCACCACCCACCCTGAGCATGCTGGACGA
ATACAGAGTATCTGGTCACGACTGCAAGAAACTGGGCTGCTAAATAAATGTGAGCGAATT
CAAGGTCGAAAAGCCAGCCTGGAGGAAATACAGCTTGTTCATTCTGAACATCACTCACTG
TTGTATGGCACCAACCCCCTGGACGGACAGAAGCTGGACCCCAGGATACTCCTAGGTGAT
GACTCTCAAAAGTTTTTTTCCTCATTACCTTGTGGTGGACTTGGGGTGGACAGTGACACC
ATTTGGAATGAGCTACACTCGTCCGGTGCTGCACGCATGGCTGTTGGCTGTGTCATCGAG
CTGGCTTCCAAAGTGGCCTCAGGAGAGCTGAAGAATGGGTTTGCTGTTGTGAGGCCCCCT
GGCCATCACGCTGAAGAATCCACAGCCATGGGGTTCTGCTTTTTTAATTCAGTTGCAATT
ACCGCCAAATACTTGAGAGACCAACTAAATATAAGCAAGATATTGATTGTAGATCTGGAT
GTTCACCATGGAAACGGTACCCAGCAGGCCTTTTATGCTGACCCCAGCATCCTGTACATT
TCACTCCATCGCTATGATGAAGGGAACTTTTTCCCTGGCAGTGGAGCCCCAAATGAGGTT
GGAACAGGCCTTGGAGAAGGGTACAATATAAATATTGCCTGGACAGGTGGCCTTGATCCT
CCCATGGGAGATGTTGAGTACCTTGAAGCATTCAGGACCATCGTGAAGCCTGTGGCCAAA
GAGTTTGATCCAGACATGGTCTTAGTATCTGCTGGATTTGATGCATTGGAAGGCCACACC
CCTCCTCTAGGAGGGTACAAAGTGACGGCAAAATGTTTTGGTCATTTGACGAAGCAATTG
ATGACATTGGCTGATGGACGTGTGGTGTTGGCTCTAGAAGGAGGACATGATCTCACAGCC
ATCTGTGATGCATCAGAAGCCTGTGTAAATGCCCTTCTAGGAAATGAGCTGGAGCCACTT
GCAGAAGATATTCTCCACCAAAGCCCGAATATGAATGCTGTTATTTCTTTACAGAAGATC
ATTGAAATTCAAAGTATGTCTTTAAAGTTCTCTTAA
Target 3 GenBank Gene ID
Target 3 GeneCard ID HDAC9 Link Image
Target 3 GenAtlas ID HDAC9 Link Image
Target 3 HGNC ID HGNC:14065 Link Image
Target 3 Chromosome Location 7
Target 3 Locus 7p21.1
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Sparrow DB, Miska EA, Langley E, Reynaud-Deonauth S, Kotecha S, Towers N, Spohr G, Kouzarides T, Mohun TJ: MEF-2 function is modified by a novel co-repressor, MITR. EMBO J. 1999 Sep 15;18(18):5085-98. [PubMed Link Image]
  2. Miska EA, Karlsson C, Langley E, Nielsen SJ, Pines J, Kouzarides T: HDAC4 deacetylase associates with and represses the MEF2 transcription factor. EMBO J. 1999 Sep 15;18(18):5099-107. [PubMed Link Image]
  3. Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J, Yang XJ: HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor. Mol Cell Biol. 1999 Nov;19(11):7816-27. [PubMed Link Image]
  4. Zhou X, Marks PA, Rifkind RA, Richon VM: Cloning and characterization of a histone deacetylase, HDAC9. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10572-7. Epub 2001 Sep 4. [PubMed Link Image]
  5. Petrie K, Guidez F, Howell L, Healy L, Waxman S, Greaves M, Zelent A: The histone deacetylase 9 gene encodes multiple protein isoforms. J Biol Chem. 2003 May 2;278(18):16059-72. Epub 2003 Feb 17. [PubMed Link Image]
  6. David D, Cardoso J, Marques B, Marques R, Silva ED, Santos H, Boavida MG: Molecular characterization of a familial translocation implicates disruption of HDAC9 and possible position effect on TGFbeta2 in the pathogenesis of Peters' anomaly. Genomics. 2003 May;81(5):489-503. [PubMed Link Image]
  7. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [PubMed Link Image]
  8. Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 1998 Oct 30;5(5):277-86. [PubMed Link Image]
Target 3 Drug References
  1. Ylisastigui L, Archin NM, Lehrman G, Bosch RJ, Margolis DM: Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression. AIDS. 2004 May 21;18(8):1101-8. [PubMed Link Image]
  2. Michaelis M, Kohler N, Reinisch A, Eikel D, Gravemann U, Doerr HW, Nau H, Cinatl J Jr: Increased human cytomegalovirus replication in fibroblasts after treatment with therapeutical plasma concentrations of valproic acid. Biochem Pharmacol. 2004 Aug 1;68(3):531-8. [PubMed Link Image]
  3. Kanai H, Sawa A, Chen RW, Leeds P, Chuang DM: Valproic acid inhibits histone deacetylase activity and suppresses excitotoxicity-induced GAPDH nuclear accumulation and apoptotic death in neurons. Pharmacogenomics J. 2004;4(5):336-44. [PubMed Link Image]
  4. Stockhausen MT, Sjolund J, Manetopoulos C, Axelson H: Effects of the histone deacetylase inhibitor valproic acid on Notch signalling in human neuroblastoma cells. Br J Cancer. 2005 Feb 28;92(4):751-9. [PubMed Link Image]
  5. Beutler AS, Li S, Nicol R, Walsh MJ: Carbamazepine is an inhibitor of histone deacetylases. Life Sci. 2005 May 13;76(26):3107-15. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.