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Showing drug card for Hydralazine (DB01275)

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Version 2.5
Creation Date 2007-05-16 20:38:00
Update Date 2009-06-23 18:06:22
Primary Accession Number DB01275
Secondary Accession Number Not Available
Name Hydralazine
Drug Type
  • Approved
  • Small Molecule
Description A direct-acting vasodilator that is used as an antihypertensive agent. [PubChem]
Synonyms
  1. Hydralazine hydrochloride
Brand Names
  1. Apresoline
Brand Mixtures
  1. BiDil (isosorbide dinitrate + hydralazine hydrochloride)
Chemical IUPAC Name phthalazin-1-ylhydrazine
Chemical Formula C8H8N4
Chemical Structure Structure
CAS Registry Number 86-54-4
InChI Identifier InChI=1/C8H8N4/c9-11-8-7-4-2-1-3-6(7)5-10-12-8/h1-5H,9H2,(H,11,12)/f/h11H
InChI Key RPTUSVTUFVMDQK-WXRBYKJCCB
KEGG Drug D01302 Link Image
KEGG Compound C07040 Link Image
PubChem Compound 3637 Link Image
PubChem Substance 9252 Link Image
ChEBI ID Not Available
PharmGKB ID PA449894 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 00441619 Link Image
RxList Link http://www.rxlist.com/cgi/generic/hydralazine.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Hydralazine Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 160.1759
Monoisotopic Molecular Weight 160.0749
State Solid
Melting Point 172-173 oC
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 2.64e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 0.7 Source: PhysProp
Predicted LogP 0.66 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -1.78 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
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 Not Available
Isomeric SMILES NNC1=NN=CC2=CC=CC=C12
Canonical SMILES NNC1=NN=CC2=CC=CC=C12
Drug Category
  • Antihypertensive Agents
  • Vasodilator Agents
ATC Codes
AHFS Codes
  • 24:08.20
Indication For the treatment of essential hypertension, alone or as an adjunct. Also for the management of moderate to severe hypertension, congestive heart failure, and hypertension secondary to pre-eclampsia/eclampsia.
Pharmacology A vasodilator, hydralazine works by relaxing blood vessels (arterioles more than venules) and increasing the supply of blood and oxygen to the heart while reducing its workload. It also functions as an antioxidant. It inhibits membrane-bound enzymes that form reactive oxygen species, such as superoxides. Excessive superoxide counteracts NO-induced vasodilation. It is commonly used in the condition of pregnancy called preeclampsia.
Mechanism of Action Although the precise mechanism of action of hydralazine is not fully understood, the major effects are on the cardiovascular system. Hydralazine apparently lowers blood pressure by exerting a peripheral vasodilating effect through a direct relaxation of vascular smooth muscle. Hydralazine, by altering cellular calcium metabolism, interferes with the calcium movements within the vascular smooth muscle that are responsible for initiating or maintaining the contractile state.
Absorption Hydralazine is rapidly and extensively absorbed (up to 90%) from the gastrointestinal tract and undergoes extensive first-pass metabolism by genetic polymorphic acetylation. Oral bioavailability of hydralazine is dependent upon acetylator phenotype. Bioavailability is approximately 31% in slow acetylators and 10% in fast acetylators.
Toxicity Oral LD50 in rats: 173 and 187 mg/kg
Protein Binding 87%
Biotransformation Hydralazine, when administered orally, undergoes extensive first-pass metabolism by genetic polymorphic acetylation, which is responsible for a threefold range of oral bioavailability. Intravenously administered hydralazine does not undergo first-pass metabolism and, therefore, is not affected by acetylator phenotype. After the drug reaches the systemic circulation, it is combined with endogenous aldehydes and ketones, including pyruvic acid, to form hydrazone metabolites. The active metabolites, hydralazine acetonide hydrazone and hydralazine pyruvate hydrazone, are equipotent with the parent, hydralazine.
Half Life 3 to 7 hours
Dosage Forms
Form Route
Powder, for solution Intravenous
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Wikipedia Link Image
  2. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Prolyl 4-hydroxylase subunit alpha-1
  2. Membrane copper amine oxidase
Drug Target 1 [top]
Target 1 ID 67
Target 1 Name Prolyl 4-hydroxylase subunit alpha-1
Target 1 Synonyms
  1. 4-PH alpha-1
  2. EC 1.14.11.2
  3. Procollagen-proline,2-oxoglutarate-4-dioxygenase alpha-1 subunit
  4. Prolyl 4-hydroxylase subunit alpha-1 precursor
Target 1 Gene Name P4HA1
Target 1 Protein Sequence >Prolyl 4-hydroxylase alpha-1 subunit precursor 
MIWYILIIGILLPQSLAHPGFFTSIGQMTDLIHTEKDLVTSLKDYIKAEEDKLEQIKKWA
EKLDRLTSTATKDPEGFVGHPVNAFKLMKRLNTEWSELENLVLKDMSDGFISNLTIQRQY
FPNDEDQVGAAKALLRLQDTYNLDTDTISKGNLPGVKHKSFLTAEDCFELGKVAYTEADY
YHTELWMEQALRQLDEGEISTIDKVSVLDYLSYAVYQQGDLDKALLLTKKLLELDPEHQR
ANGNLKYFEYIMAKEKDVNKSASDDQSDQKTTPKKKGVAVDYLPERQKYEMLCRGEGIKM
TPRRQKKLFCRYHDGNRNPKFILAPAKQEDEWDKPRIIRFHDIISDAEIEIVKDLAKPRL
RRATISNPITGDLETVHYRISKSAWLSGYENPVVSRINMRIQDLTGLDVSTAEELQVANY
GVGGQYEPHFDFARKDEPDAFKELGTGNRIATWLFYMSDVSAGGATVFPEVGASVWPKKG
TAVFWYNLFASGEGDYSTRHAACPVLVGNKWVSNKWLHERGQEFRRPCTLSELE
Target 1 Number of Residues 542
Target 1 Molecular Weight 61050
Target 1 Theoretical pI 5.84
Target 1 GO Classification
Function
binding
catalytic activity
oxidoreductase activity
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors
Process
physiological process
metabolism
macromolecule metabolism
protein metabolism
Component
Not Available
Target 1 General Function Involved in oxidoreductase activity
Target 1 Specific Function Catalyzes the posttranslational formation of 4- hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins
Target 1 Pathways
Name SMPDB Link KEGG Link
Arginine and proline metabolism SMP00020 Link Image map00330 Link Image
Target 1 Reactions
  • procollagen L-proline + 2-oxoglutarate + O2 = procollagen trans-4-hydroxy-L-proline + succinate + CO2
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-17
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 190786 Link Image
Target 1 UniProtKB/Swiss-Prot ID P13674 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name P4HA1_HUMAN Link Image
Target 1 PDB ID 1TJC Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Endoplasmic reticulum
  • endoplasmic reticulum lumen
Target 1 Gene Sequence >1605 bp 
ATGATCTGGTATATATTAATTATAGGAATTCTGCTTCCCCAGTCTTTGGCTCATCCAGGC
TTTTTTACTTCAATTGGTCAGATGACTGATTTGATCCATACTGAGAAAGATCTGGTGACT
TCTCTGAAAGATTATATTAAGGCAGAAGAGGACAAGTTAGAACAAATAAAAAAATGGGCA
GAGAAGTTAGATCGGCTAACTAGTACAGCGACAAAAGATCCAGAAGGATTTGTTGGGCAT
CCAGTAAATGCATTCAAATTAATGAAACGTCTGAATACTGAGTGGAGTGAGTTGGAGAAT
CTGGTCCTTAAGGATATGTCAGATGGCTTTATCTCTAACCTAACCATTCAGAGACCAGTA
CTTTCTAATGATGAAGATCAGGTTGGGGCAGCCAAAGCTCTGTTACGTCTCCAGGATACC
TACAATTTGGATACAGATACCATCTCAAAGGGTAATCTTCCAGGAGTGAAACACAAATCT
TTTCTAACGGCTGAGGACTGCTTTGAGTTGGGCAAAGTGGCCTATACAGAAGCAGATTAT
TACCATACGGAACTGTGGATGGAACAAGCCCTAAGGCAACTGGATGAAGGCGAGATTTCT
ACCATAGATAAAGTCTCTGTTCTAGATTATTTGAGCTATGCGGTATATCAGCAGGGAGAC
CTGGATAAGGCACTTTTGCTCACAAAGAAGCTTCTTGAACTAGATCCTGAACATCAGAGA
GCTAATGGTAACTTAAAATATTTTGAGTATATAATGGCTAAAGAAAAAGATGTCAATAAG
TCTGCTTCAGATGACCAATCTGATCAGAAAACTACACCAAAGAAAAAAGGGGTTGCTGTG
GATTACCTGCCAGAGAGACAGAAGTACGAAATGCTGTGCCGTGGGGAGGGTATCAAAATG
ACCCCTCGGAGACAGAAAAAACTCTTTTGCCGCTACCATGATGGAAACCGTAATCCTAAA
TTTATTCTGGCTCCAGCTAAACAGGAGGATGAATGGGACAAGCCTCGTATTATTCGCTTC
CATGATATTATTTCTGATGCAGAAATTGAAATCGTCAAAGACCTAGCAAAACCAAGGCTG
AGCCGAGCTACAGTACATGACCCTGAGACTGGAAAATTGACCACAGCACAGTACAGAGTA
TCTAAGAGTGCCTGGCTCTCTGGCTATGAAAATCCTGTGGTGTCTCGAATTAATATGAGA
ATACAAGATCTAACAGGACTAGATGTTTCCACAGCAGAGGAATTACAGGTAGCAAATTAT
GGAGTTGGAGGACAGTATGAACCCCATTTTGACTTTGCACGGAAAGATGAGCCAGATGCT
TTCAAAGAGCTGGGGACAGGAAATAGAATTGCTACATGGCTGTTTTATATGAGTGATGTG
TCTGCAGGAGGAGCCACTGTTTTTCCTGAAGTTGGAGCTAGTGTTTGGCCCAAAAAAGGA
ACTGCTGTTTTCTGGTATAATCTGTTTGCCAGTGGAGAAGGAGATTATAGTACACGGCAT
GCAGCCTGTCCAGTGCTAGTTGGCAACAAATGGGTATCCAATAAATGGCTCCATGAACGT
GGACAAGAATTTCGAAGACCTTGTACGTTGTCAGAATTGGAATGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID P4HA1 Link Image
Target 1 GenAtlas ID P4HA1 Link Image
Target 1 HGNC ID HGNC:8546 Link Image
Target 1 Chromosome Location 10
Target 1 Locus 10q21.3-q23.1
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Helaakoski T, Vuori K, Myllyla R, Kivirikko KI, Pihlajaniemi T: Molecular cloning of the alpha-subunit of human prolyl 4-hydroxylase: the complete cDNA-derived amino acid sequence and evidence for alternative splicing of RNA transcripts. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4392-6. [PubMed Link Image]
  2. Helaakoski T, Veijola J, Vuori K, Rehn M, Chow LT, Taillon-Miller P, Kivirikko KI, Pihlajaniemi T: Structure and expression of the human gene for the alpha subunit of prolyl 4-hydroxylase. The two alternatively spliced types of mRNA correspond to two homologous exons the sequences of which are expressed in a variety of tissues. J Biol Chem. 1994 Nov 11;269(45):27847-54. [PubMed Link Image]
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 1483
Target 2 Name Membrane copper amine oxidase
Target 2 Synonyms
  1. EC 1.4.3.6
  2. HPAO
  3. SSAO
  4. Semicarbazide-sensitive amine oxidase
  5. VAP-1
  6. Vascular adhesion protein 1
Target 2 Gene Name AOC3
Target 2 Protein Sequence >Membrane copper amine oxidase 
MNQKTILVLLILAVITIFALVCVLLVGRGGDGGEPSQLPHCPSVSPSAQPWTHPGQSQLF
ADLSREELTAVMRFLTQRLGPGLVDAAQARPSDNCVFSVELQLPPKAAALAHLDRGSPPP
AREALAIVFFGRQPQPNVSELVVGPLPHPSYMRDVTVERHGGPLPYHRRPVLFQEYLDID
QMIFNRELPQASGLLHHCCFYKHRGRNLVTMTTAPRGLQSGDRATWFGLYYNISGAGFFL
HHVGLELLVNHKALDPARWTIQKVFYQGRYYDSLAQLEAQFEAGLVNVVLIPDNGTGGSW
SLKSPVPPGPAPPLQFYPQGPRFSVQGSRVASSLWTFSFGLGAFSGPRIFDVRFQGERLV
YEISLQEALAIYGGNSPAAMTTRYVDGGFGMGKYTTPLTRGVDCPYLATYVDWHFLLESQ
APKTIRDAFCVFEQNQGLPLRRHHSDLYSHYFGGLAETVLVVRSMSTLLNYDYVWDTVFH
PSGAIEIRFYATGYISSAFLFGATGKYGNQVSEHTLGTVHTHSAHFKVDLDVAGLENWVW
AEDMVFVPMAVPWSPEHQLQRLQVTRKLLEMEEQAAFLVGSATPRYLYLASNHSNKWGHP
RGYRIQMLSFAGEPLPQNSSMARGFSWERYQLAVTQRKEEEPSSSSVFNQNDPWAPTVDF
SDFINNETIAGKDLVAWVTAGFLHIPHAEDIPNTVTVGNGVGFFLRPYNFFDEDPSFYSA
DSIYFRGDQDAGACEVNPLACLPQAAACAPDLPAFSHGGFSHN
Target 2 Number of Residues 775
Target 2 Molecular Weight 84623
Target 2 Theoretical pI 6.51
Target 2 GO Classification
Function
binding
ion binding
cation binding
transition metal ion binding
copper ion binding
Process
Not Available
Component
Not Available
Target 2 General Function Secondary metabolites biosynthesis, transport and catabolism
Target 2 Specific Function Cell adhesion protein that participates in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin- independent fashion. Has a monoamine oxidase activity
Target 2 Pathways
Name SMPDB Link KEGG Link
Glycine, serine and threonine metabolism SMP00004 Link Image map00260 Link Image
Target 2 Reactions
  • RCH2NH2 + H2O + O2 = RCHO + NH3 + H2O2
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 6-26
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 1399032 Link Image
Target 2 UniProtKB/Swiss-Prot ID Q16853 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name AOC3_HUMAN Link Image
Target 2 PDB ID 1PU4 Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Membrane
  • single-pass type II membrane protein
Target 2 Gene Sequence >2292 bp 
ATGAACCAGAAGACAATCCTCGTGCTCCTCATTCTGGCCGTCATCACCATCTTTGCCTTG
GTTTGTGTCCTGCTGGTGGGCAGGGGTGGAGATGGGGGTGAACCCAGCCAGCTTCCCCAT
TGCCCCTCTGTATCTCCCAGTGCCCAGCCTTGGACACACCCTGGCCAGAGCCAGCTGTTT
GCAGACCTGAGCCGAGAGGAGCTGACGGCTGTGATGCGCTTTCTGACCCAGCGGCTGGGG
CCAGGGCTGGTGGATGCAGCCCAGGCCCGGCCCTCGGACAACTGTGTCTTCTCAGTGGAG
TTGCAGCTGCCTCCCAAGGCTGCAGCCCTGGCTCACTTGGACAGGGGGAGCCCCCCACCT
GCCCGGGAGGCACTGGCCATCGTCTTCTTTGGCAGGCAACCCCAGCCCAACGTGAGTGAG
CTGGTGGTGGGGCCACTGCCTCACCCCTCCTACATGCGGGACGTGACTGTGGAGCGTCAT
GGAGGCCCCCTGCCCTATCACCGACGCCCCGTGCTGTTCCAAGAGTACCTGGACATAGAC
CAGATGATCTTCAACAGAGAGCTGCCCCAGGCTTCTGGGCTTCTCCACCACTGTTGCTTC
TACAAGCACCGGGGACGGAACCTGGTGACAATGACCACGGCTCCCCGTGGTCTGCAATCA
GGGGACCGGGCCACCTGGTTTGGCCTCTACTACAACATCTCGGGCGCTGGGTTCTTCCTG
CACCACGTGGGCTTGGAGCTGCTAGTGAACCACAAGGCCCTTGACCCTGCCCGCTGGACT
ATCCAGAAGGTGTTCTATCAAGGCCGCTACTACGACAGCCTGGCCCAGCTGGAGGCCCAG
TTTGAGGCCGGCCTGGTGAATGTGGTGCTGATCCCAGACAATGGCACAGGTGGGTCCTGG
TCCCTGAAGTCCCCTGTGCCCCCGGGTCCAGCTCCCCCTCTACAGTTCTATCCCCAAGGC
CCCCGCTTCAGTGTCCAGGGAAGTCGAGTGGCCTCCTCACTGTGGACTTTCTCCTTTGGC
CTCGGAGCATTCAGTGGCCCAAGGATCTTTGACGTTCGCTTCCAAGGAGAAAGACTAGTT
TATGAGATAAGCCTCCAAGAGGCCTTGGCCATCTATGGTGGAAATTCCCCAGCAGCAATG
ACGACCCGCTATGTGGATGGAGGCTTTGGCATGGGCAAGTACACCACGCCCCTGACCCGT
GGGGTGGACTGCCCCTACTTGGCCACCTACGTGGACTGGCACTTCCTTTTGGAGTCCCAG
GCCCCCAAGACAATACGTGATGCCTTTTGTGTGTTTGAACAGAACCAGGGCCTCCCCCTG
CGGCGACACCACTCAGATCTCTACTCGCACTACTTTGGGGGTCTTGCGGAAACGGTGCTG
GTCGTCAGATCTATGTCCACCTTGCTCAACTATGACTATGTGTGGGATACGGTCTTCCAC
CCCAGTGGGGCCATAGAAATACGATTCTATGCCACGGGCTACATCAGCTCGGCATTCCTC
TTTGGTGCTACTGGGAAGTACGGGAACCAAGTGTCAGAGCACACCCTGGGCACGGTCCAC
ACCCACAGCGCCCACTTCAAGGTGGATCTGGATGTAGCAGGACTGGAGAACTGGGTCTGG
GCCGAGGATATGGTCTTTGTCCCCATGGCTGTGCCCTGGAGCCCTGAGCACCAGCTGCAG
AGGCTGCAGGTGACCCGGAAGCTGCTGGAGATGGAGGAGCAGGCCGCCTTCCTCGTGGGA
AGCGCCACCCCTCGCTACCTGTACCTGGCCAGCAACCACAGCAACAAGTGGGGTCACCCC
CGGGGCTACCGCATCCAGATGCTCAGCTTTGCTGGAGAGCCGCTGCCCCAAAACAGCTCC
ATGGCGAGAGGCTTCAGCTGGGAGAGGTACCAGCTGGCTGTGACCCAGCGGAAGGAGGAG
GAGCCCAGTAGCAGCAGCGTTTTCAATCAGAATGACCCTTGGGCCCCCACTGTGGATTTC
AGTGACTTCATCAACAATGAGACCATTGCTGGAAAGGATTTGGTGGCCTGGGTGACAGCT
GGTTTTCTGCATATCCCACATGCAGAGGACATTCCTAACACAGTGACTGTGGGGAACGGC
GTGGGCTTCTTCCTCCGACCCTATAACTTCTTTGACGAAGACCCCTCCTTCTACTCTGCC
GACTCCATCTACTTCCGAGGGGACCAGGATGCTGGGGCCTGCGAGGTCAACCCCCTAGCT
TGCCTGCCCCAGGCTGCTGCCTGTGCCCCCGACCTCCCTGCCTTCTCCCACGGGGGCTTC
TCTCACAACTAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID AOC3 Link Image
Target 2 GenAtlas ID AOC3 Link Image
Target 2 HGNC ID HGNC:550 Link Image
Target 2 Chromosome Location 17
Target 2 Locus 17q21
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Zhang X, McIntire WS: Cloning and sequencing of a copper-containing, topa quinone-containing monoamine oxidase from human placenta. Gene. 1996 Nov 14;179(2):279-86. [PubMed Link Image]
  2. Smith DJ, Salmi M, Bono P, Hellman J, Leu T, Jalkanen S: Cloning of vascular adhesion protein 1 reveals a novel multifunctional adhesion molecule. J Exp Med. 1998 Jul 6;188(1):17-27. [PubMed Link Image]
Target 2 Drug References
  1. Claud P, Padovani P, Guichard JP, Artur Y, Laine R: Involvement of semicarbazide-sensitive amine oxidase in tresperimus metabolism in human and in rat. Drug Metab Dispos. 2001 May;29(5):735-41. [PubMed Link Image]
  2. Vidrio H, Medina M, Gonzalez-Romo P, Lorenzana-Jimenez M, Diaz-Arista P, Baeza A: Semicarbazide-sensitive amine oxidase substrates potentiate hydralazine hypotension: possible role of hydrogen peroxide. J Pharmacol Exp Ther. 2003 Nov;307(2):497-504. Epub 2003 Sep 11. [PubMed Link Image]
  3. Vidrio H: Semicarbazide-sensitive amine oxidase: role in the vasculature and vasodilation after in situ inhibition. Auton Autacoid Pharmacol. 2003 Oct-Dec;23(5-6):275-83. [PubMed Link Image]
  4. Vidrio H, Medina M: 2-bromoethylamine, a suicide inhibitor of semicarbazide-sensitive amine oxidase, increases hydralazine hypotension in rats. J Cardiovasc Pharmacol. 2005 Sep;46(3):316-24. [PubMed Link Image]
  5. Vidrio H, Medina M: Hypotensive effect of hydroxylamine, an endogenous nitric oxide donor and SSAO inhibitor. J Neural Transm. 2007;114(6):863-5. Epub 2007 Mar 26. [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.