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Showing drug card for Celecoxib (DB00482)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:47:44
Primary Accession Number DB00482
Secondary Accession Number
  • APRD00373
Name Celecoxib
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. It is marketed by Pfizer under the brand name Celebrex. In some countries, it is branded Celebra. Celecoxib is available by prescription in capsule form.
Synonyms
  1. Celocoxib
  2. celecoxib
Brand Names
  1. Celebra
  2. Celebrex
Brand Mixtures Not Available
Chemical IUPAC Name 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
Chemical Formula C17H14F3N3O2S
Chemical Structure Structure
CAS Registry Number 169590-42-5
InChI Identifier InChI=1/C17H14F3N3O2S/c1-11-2-4-12(5-3-11)15-10-16(17(18,19)20)22-23(15)13-6-8-14(9-7-13)26(21,24)25/h2-10H,1H3,(H2,21,24,25)/f/h21H2
InChI Key RZEKVGVHFLEQIL-QVUQFMIFCW
KEGG Drug D00567 Link Image
KEGG Compound C07589 Link Image
PubChem Compound 2662 Link Image
PubChem Substance 205043 Link Image
ChEBI ID 3520 Link Image
PharmGKB ID PA448871 Link Image
HET ID CEL Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02239941 Link Image
RxList Link http://www.rxlist.com/cgi/generic/coxib.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Celecoxib Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Paradkar et al., Drug Dev Ind Pharm. 2003 29(7):739-44
Average Molecular Weight 381.3720
Monoisotopic Molecular Weight 381.0759
State Solid
Melting Point 157-158oC
Experimental Water Solubility Very low water solubility (3.3 mg/L) Source: PhysProp
Predicted Water Solubility 5.03e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3.9 Source: PhysProp
Predicted LogP 3.99 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.88 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 CC1=CC=C(C=C1)C1=CC(=NN1C1=CC=C(C=C1)S(N)(=O)=O)C(F)(F)F
Canonical SMILES CC1=CC=C(C=C1)C1=CC(=NN1C1=CC=C(C=C1)S(N)(=O)=O)C(F)(F)F
Drug Category
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
ATC Codes
AHFS Codes
  • 28:08.04.08
Indication For relief and management of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, acute pain, primary dysmenorrhea and oral adjunct to usual care for patients with familial adenomatous polyposis
Pharmacology Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Celecoxib is used to treat rheumatoid arthritis, osteoarthritis, and familial adenomatous polyposis (FAP). Because of its lack of platelet effects, celecoxib is not a substitute for aspirin for cardiovascular prophylaxis. It is not known if there are any effects of celecoxib on platelets that may contribute to the increased risk of serious cardiovascular thrombotic adverse events associated with the use of celecoxib. Inhibition of PGE2 synthesis may lead to sodium and water retention through increased reabsorption in the renal medullary thick ascending loop of Henle and perhaps other segments of the distal nephron. In the collecting ducts, PGE2 appears to inhibit water reabsorption by counteracting the action of antidiuretic hormone.
Mechanism of Action The mechanism of action of celecoxib is believed to be due to inhibition of prostaglandin synthesis. Unlike most NSAIDs, which inhibit both types of cyclooxygenases (COX-1 and COX-2), celecoxib is a selective noncompetitive inhibitor of cyclooxygenase-2 (COX-2) enzyme. It binds with its polar sulfonamide side chain to a hydrophilic side pocket region close to the active COX-2 binding site. Both COX-1 and COX-2 catalyze the conversion of arachidonic acid to prostaglandin (PG) H2, the precursor of PGs and thromboxane.
Absorption Well absorbed in the gastrointestinal tract. When taken with a high fat meal, peak plasma levels are delayed for about 1 to 2 hours with an increase in total absorption (AUC) of 10% to 20%.
Toxicity Symptoms of overdose include breathing difficulties, coma, drowsiness, gastrointestinal bleeding, high blood pressure, kidney failure, nausea, sluggishness, stomach pain, and vomiting.
Protein Binding 97%, primarily to albumin and, to a lesser extent, a1-acid glycoprotein.
Biotransformation Hepatic. Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites, a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate, have been identified in human plasma. These metabolites are inactive as COX-1 or COX-2 inhibitors.
Half Life Approximately 11 hours.
Dosage Forms
Form Route
Capsule Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol Increases the anticoagulant effect
Anisindione Increases the anticoagulant effect
Dicumarol Increases the anticoagulant effect
Fluconazole Fluconazole increases the effect of celecoxib
Lithium The COX-2 inhibitor increases serum levels of lithium
Rifampin Decreased levels/effect of the NSAID
Warfarin Increases the anticoagulant effect
Food Interactions
  • Take without regard to meals.
  • Taking this product with a high-fat meal will delay the Cmax, but total absorption will be increased by 10 to 20%.
Pathways
Name SMPDB Link KEGG Link
Celecoxib Pathway SMP00096 Link Image
General References
  1. Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS: Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA. 2000 Sep 13;284(10):1247-55. [PubMed Link Image]
  2. Malhotra S, Shafiq N, Pandhi P: COX-2 inhibitors: a CLASS act or Just VIGORously promoted. MedGenMed. 2004 Mar 23;6(1):6. [PubMed Link Image]
  3. Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M: Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005 Mar 17;352(11):1071-80. Epub 2005 Feb 15. [PubMed Link Image]
  4. Yelland MJ, Nikles CJ, McNairn N, Del Mar CB, Schluter PJ, Brown RM: Celecoxib compared with sustained-release paracetamol for osteoarthritis: a series of n-of-1 trials. Rheumatology (Oxford). 2007 Jan;46(1):135-40. Epub 2006 Jun 15. [PubMed Link Image]
  5. Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET: Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006 Aug 31;355(9):873-84. [PubMed Link Image]
  6. Drugs.com Link Image
  7. Wikipedia Link Image
  8. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2C9 (CYP2C9)
  2. Cytochrome P450 2D6 (CYP2D6)
Targets
  1. Prostaglandin G/H synthase 2
  2. 3-phosphoinositide-dependent protein kinase 1
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2C9 (CYP2C9)
Enzyme 1 Gene Name CYP2C9
Enzyme 1 SwissProt ID P11712 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P11712|CP2C9_HUMAN Cytochrome P450 2C9 (EC 1.14.13.80) 
MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV
YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM
KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID
LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK
KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP
PFYQLCFIPV
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 2D6 (CYP2D6)
Enzyme 2 Gene Name CYP2D6
Enzyme 2 SwissProt ID P10635 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P10635|CP2D6_HUMAN Cytochrome P450 2D6 (EC 1.14.14.1) 
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF
LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK
AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV
LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA
DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI
HEVQRFGDIVPLGMTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF
LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV
FAFLVSPSPYELCAVPR
Drug Target 1 [top]
Target 1 ID 290
Target 1 Name Prostaglandin G/H synthase 2
Target 1 Synonyms
  1. COX-2
  2. Cyclooxygenase- 2
  3. EC 1.14.99.1
  4. PGH synthase 2
  5. PGHS-2
  6. PHS II
  7. Prostaglandin G/H synthase 2 precursor
  8. Prostaglandin H2 synthase 2
  9. Prostaglandin-endoperoxide synthase 2
Target 1 Gene Name PTGS2
Target 1 Protein Sequence >Prostaglandin G/H synthase 2 precursor 
MLARALLLCAVLALSHTANPCCSHPCQNRGVCMSVGFDQYKCDCTRTGFYGENCSTPEFL
TRIKLFLKPTPNTVHYILTHFKGFWNVVNNIPFLRNAIMSYVLTSRSHLIDSPPTYNADY
GYKSWEAFSNLSYYTRALPPVPDDCPTPLGVKGKKQLPDSNEIVEKLLLRRKFIPDPQGS
NMMFAFFAQHFTHQFFKTDHKRGPAFTNGLGHGVDLNHIYGETLARQRKLRLFKDGKMKY
QIIDGEMYPPTVKDTQAEMIYPPQVPEHLRFAVGQEVFGLVPGLMMYATIWLREHNRVCD
VLKQEHPEWGDEQLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNKQFQYQ
NRIAAEFNTLYHWHPLLPDTFQIHDQKYNYQQFIYNNSILLEHGITQFVESFTRQIAGRV
AGGRNVPPAVQKVSQASIDQSRQMKYQSFNEYRKRFMLKPYESFEELTGEKEMSAELEAL
YGDIDAVELYPALLVEKPRPDAIFGETMVEVGAPFSLKGLMGNVICSPAYWKPSTFGGEV
GFQIINTASIQSLICNNVKGCPFTSFSVPDPELIKTVTINASSSRSGLDDINPTVLLKER
STEL
Target 1 Number of Residues 614
Target 1 Molecular Weight 68997
Target 1 Theoretical pI 7.41
Target 1 GO Classification
Function
antioxidant activity
peroxidase activity
Process
Not Available
Component
Not Available
Target 1 General Function Involved in peroxidase activity
Target 1 Specific Function May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity
Target 1 Pathways
Name SMPDB Link KEGG Link
Prostaglandin and leukotriene metabolism map00590 Link Image
Target 1 Reactions
  • arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O
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 291988 Link Image
Target 1 UniProtKB/Swiss-Prot ID P35354 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name PGH2_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Microsome
  • microsomal membrane
  • peripheral membrane protein
Target 1 Gene Sequence >1815 bp 
ATGCTCGCCCGCGCCCTGCTGCTGTGCGCGGTCCTGGCGCTCAGCCATACAGCAAATCCT
TGCTGTTCCCACCCATGTCAAAACCGAGGTGTATGTATGAGTGTGGGATTTGACCAGTAT
AAGTGCGATTGTACCCGGACAGGATTCTATGGAGAAAACTGCTCAACACCGGAATTTTTG
ACAAGAATAAAATTATTTCTGAAACCCACTCCAAACACAGTGCACTACATACTTACCCAC
TTCAAGGGATTTTGGAACGTTGTGAATAACATTCCCTTCCTTCGAAATGCAATTATGAGT
TATGTGTTGACATCCAGATCACATTTGATTGACAGTCCACCAACTTACAATGCTGACTAT
GGCTACAAAAGCTGGGAAGCCTTCTCTAACCTCTCCTATTATACTAGAGCCCTTCCTCCT
GTGCCTGATGATTGCCCGACTCCCTTGGGTGTCAAAGGTAAAAAGCAGCTTCCTGATTCA
AATGAGATTGTGGAAAAATTGCTTCTAAGAAGAAAGTTCATCCCTGATCCCCAGGGCTCA
AACATGATGTTTGCATTCTTTGCCCAGCACTTCACGCATCAGTTTTTCAAGACAGATCAT
AAGCGAGGGCCAGCTTTCACCAACGGGCTGGGCCATGGGGTGGACTTAAATCATATTTAC
GGTGAAACTCTGGCTAGACAGCGTAAACTGCGCCTTTTCAAGGATGGAAAAATGAAATAT
CAGATAATTGATGGAGAGATGTATCCTCCCACAGTCAAAGATACTCAGGCAGAGATGATC
TACCCTCCTCAAGTCCCTGAGCATCTACGGTTTGCTGTGGGGCAGGAGGTCTTTGGTCTG
GTGCCTGGTCTGATGATGTATGCCACAATCTGGCTGCGGGAACACAACAGAGTATGCGAT
GTGCTTAAACAGGAGCATCCTGAATGGGGTGATGAGCAGTTGTTCCAGACAAGCAGGCTA
ATACTGATAGGAGAGACTATTAAGATTGTGATTGAAGATTATGTGCAACACTTGAGTGGC
TATCACTTCAAACTGAAATTTGACCCAGAACTACTTTTCAACAAACAATTCCAGTACCAA
AATCGTATTGCTGCTGAATTTAACACCCTCTATCACTGGCATCCCCTTCTGCCTGACACC
TTTCAAATTCATGACCAGAAATACAACTATCAACAGTTTATCTACAACAACTCTATATTG
CTGGAACATGGAATTACCCAGTTTGTTGAATCATTCACCAGGCAAATTGCTGGCAGGGTT
GCTGGTGGTAGGAATGTTCCACCCGCAGTACAGAAAGTATCACAGGCTTCCACTGACCAG
AGCAGGCAGATGAAATACCAGTCTTTTAATGAGTACCGCAAACGCTTTATGCTGAAGCCC
TATGAATCATTTGAAGAACTTACAGGAGAAAAGGAAATGTCTGCAGAGTTGGAAGCACTC
TATGGTGACATCGATGCTGTGGAGCTGTATCCTGCCCTTCTGGTAGAAAAGCCTCGGCCA
GATGCCATCTTTGGTGAAACCATGGTAGAAGTTGGAGCACCATTCTCCTTGAAAGGACTT
ATGGGTAATGTTATATGTTCTCCTGCCTACTGGAAGCCAAGCACTTTTGGTGGAGAAGTG
GGTTTTCAAATCATCAACACTGCCTCAATTCAGTCTCTCATCTGCAATAACGTGAAGGGC
TGTCCCTTTACTTCATTCAGTGTTCCAGATCCAGAGCTCATTAAAACAGTCACCATCAAT
GCAAGTTCTTCCCGCTCCGGACTAGATGATATCAATCCCACAGTACTACTAAAAGAACGT
TCGACTGAACTGTAG
Target 1 GenBank Gene ID
Target 1 GeneCard ID PTGS2 Link Image
Target 1 GenAtlas ID PTGS2 Link Image
Target 1 HGNC ID HGNC:9605 Link Image
Target 1 Chromosome Location 1
Target 1 Locus 1q25.2-q25.3
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Hla T, Neilson K: Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7384-8. [PubMed Link Image]
  2. Appleby SB, Ristimaki A, Neilson K, Narko K, Hla T: Structure of the human cyclo-oxygenase-2 gene. Biochem J. 1994 Sep 15;302 ( Pt 3):723-7. [PubMed Link Image]
  3. Kosaka T, Miyata A, Ihara H, Hara S, Sugimoto T, Takeda O, Takahashi E, Tanabe T: Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2. Eur J Biochem. 1994 May 1;221(3):889-97. [PubMed Link Image]
  4. Jones DA, Carlton DP, McIntyre TM, Zimmerman GA, Prescott SM: Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. J Biol Chem. 1993 Apr 25;268(12):9049-54. [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]
  2. Sigthorsson G, Simpson RJ, Walley M, Anthony A, Foster R, Hotz-Behoftsitz C, Palizban A, Pombo J, Watts J, Morham SG, Bjarnason I: COX-1 and 2, intestinal integrity, and pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in mice. Gastroenterology. 2002 Jun;122(7):1913-23. [PubMed Link Image]
  3. Scheiman JM: Outcomes studies of the gastrointestinal safety of cyclooxygenase-2 inhibitors. Cleve Clin J Med. 2002;69 Suppl 1:SI40-6. [PubMed Link Image]
  4. Reddy BS, Rao CV: Novel approaches for colon cancer prevention by cyclooxygenase-2 inhibitors. J Environ Pathol Toxicol Oncol. 2002;21(2):155-64. [PubMed Link Image]
  5. Ahmad SR, Kortepeter C, Brinker A, Chen M, Beitz J: Renal failure associated with the use of celecoxib and rofecoxib. Drug Saf. 2002;25(7):537-44. [PubMed Link Image]
  6. Lu S, Zhang X, Badawi AF, El-Sohemy A, Archer MC: Cyclooxygenase-2 inhibitor celecoxib inhibits promotion of mammary tumorigenesis in rats fed a high fat diet rich in n-6 polyunsaturated fatty acids. Cancer Lett. 2002 Oct 8;184(1):7-12. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 2180
Target 2 Name 3-phosphoinositide-dependent protein kinase 1
Target 2 Synonyms
  1. EC 2.7.11.1
  2. hPDK1
Target 2 Gene Name PDPK1
Target 2 Protein Sequence >3-phosphoinositide-dependent protein kinase 1 
MARTTSQLYDAVPIQSSVVLCSCPSPSMVRTQTESSTPPGIPGGSRQGPAMDGTAAEPRP
GAGSLQHAQPPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIK
ENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDET
CTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARAN
SFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYD
FPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFESVTWENLHQQTPPKLTA
YLPAMSEDDEDCYGNYDNLLSQFGCMQVSSSSSSHSLSASDTGLPQRSGSNIEQYIHDLD
SNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTE
GPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQ
EVWRQRYQSHPDAAVQ
Target 2 Number of Residues 565
Target 2 Molecular Weight 63152
Target 2 Theoretical pI 7.38
Target 2 GO Classification
Function
protein serine/threonine kinase activity
binding
nucleotide binding
purine nucleotide binding
adenyl nucleotide binding
ATP binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
protein kinase activity
Process
physiological process
metabolism
macromolecule metabolism
biopolymer metabolism
biopolymer modification
protein modification
protein amino acid phosphorylation
Component
Not Available
Target 2 General Function Involved in protein kinase activity
Target 2 Specific Function Phosphorylates and activates not only PKB/AKT, but also PKA, PKC-zeta, RPS6KA1 and RPS6KB1. May play a general role in signaling processes and in development. Isoform 3 is catalytically inactive
Target 2 Pathways Not Available
Target 2 Reactions
  • ATP + a protein = ADP + a phosphoprotein
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 2407613 Link Image
Target 2 UniProtKB/Swiss-Prot ID O15530 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name PDPK1_HUMAN Link Image
Target 2 PDB ID 2BIY Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Cytoplasm. Membrane
  • peripheral membrane protein. Note=Membrane-associated after cell stimulation le
Target 2 Gene Sequence >1671 bp 
ATGGCCAGGACCACCAGCCAGCTGTATGACGCCGTGCCCATCCAGTCCAGCGTGGTGTTA
TGTTCCTGCCCATCCCCATCAATGGTGAGGACCCAGACTGAGTCCAGCACGCCCCCTGGC
ATTCCTGGTGGCAGCAGGCAGGGCCCCGCCATGGACGGCACTGCAGCCGAGCCTCGGCCC
GGCGCCGGCTCCCTGCAGCATGCCCAGCCTCCGCCGCAGCCTCGGAAGAAGCGGCCTGAG
GACTTCAAGTTTGGGAAAATCCTTGGGGAAGGCTCTTTTTCCACGGTTGTCCTGGCTCGA
GAACTGGCAACCTCCAGAGAATATGCGATTAAAATTCTGGAGAAGCGACATATCATAAAA
GAGAACAAGGTCCCCTATGTAACCAGAGAGCGGGATGTCATGTCGCGCCTGGATCACCCC
TTCTTTGTTAAGCTTTACTTCACATTTCAGGACGACGAGAAGCTGTATTTCGGCCTTAGT
TATGCCAAAAATGGAGAACTACTTAAATATATTCGCAAAATCGGTTCATTCGATGAGACC
TGTACCCGATTTTACACGGCTGAGATCGTGTCTGCTTTAGAGTACTTGCACGGCAAGGGC
ATCATTCACAGGGACCTTAAACCGGAAAACATTTTGTTAAATGAAGATATGCACATCCAG
ATCACAGATTTTGGAACAGCAAAAGTCTTATCCCCAGAGAGCAAACAAGCCAGGGCCAAC
TCATTCGTGGGAACAGCGCAGTACGTTTCTCCAGAGCTGCTCACGGAGAAGTCCGCCTGT
AAGAGTTCAGACCTTTGGGCTCTTGGATGCATAATATACCAGCTTGTGGCAGGACTCCCA
CCATTCCGAGCTGGAAACGAGTATCTTATATTTCAGAAGATCATTAAGTTGGAATATGAC
TTTCCAGAAAAATTCTTCCCTAAGGCAAGAGACCTCGTGGAGAAACTTTTGGTTTTAGAT
GCCACAAAGCGGTTAGGCTGTGAGGAAATGGAAGGATACGGACCTCTTAAAGCACACCCG
TTCTTCGAGTCCGTCACGTGGGAGAACCTGCACCAGCAGACGCCTCCGAAGCTCACCGCT
TACCTGCCGGCTATGTCGGAAGACGACGAGGACTGCTATGGCAATTATGACAATCTCCTG
AGCCAGTTTGGCTGCATGCAGGTGTCTTCGTCCTCCTCCTCACACTCCCTGTCAGCCTCC
GACACGGGCCTGCCCCAGAGGTCAGGCAGCAACATAGAGCAGTACATTCACGATCTGGAC
TCGAACTCCTTTGAACTGGACTTACAGTTTTCCGAAGATGAGAAGAGGTTGTTGTTGGAG
AAGCAGGCTGGCGGAAACCCTTGGCACCAGTTTGTAGAAAATAATTTAATACTAAAGATG
GGCCCAGTGGATAAGCGGAAGGGTTTATTTGCAAGACGACGACAGCTGTTGCTCACAGAA
GGACCACATTTATATTATGTGGATCCTGTCAACAAAGTTCTGAAAGGTGAAATTCCTTGG
TCACAAGAACTTCGACCAGAGGCCAAGAATTTTAAAACTTTCTTTGTCCACACGCCTAAC
AGGACGTATTATCTGATGGACCCCAGCGGGAACGCACACAAGTGGTGCAGGAAGATCCAG
GAGGTTTGGAGGCAGCGATACCAGAGCCACCCGGACGCCGCTGTGCAGTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID PDPK1 Link Image
Target 2 GenAtlas ID PDPK1 Link Image
Target 2 HGNC ID HGNC:8816 Link Image
Target 2 Chromosome Location 16
Target 2 Locus 16p13.3
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Paradis S, Ailion M, Toker A, Thomas JH, Ruvkun G: A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans. Genes Dev. 1999 Jun 1;13(11):1438-52. [PubMed Link Image]
  2. Casamayor A, Morrice NA, Alessi DR: Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo. Biochem J. 1999 Sep 1;342 ( Pt 2):287-92. [PubMed Link Image]
  3. Park J, Hill MM, Hess D, Brazil DP, Hofsteenge J, Hemmings BA: Identification of tyrosine phosphorylation sites on 3-phosphoinositide-dependent protein kinase-1 and their role in regulating kinase activity. J Biol Chem. 2001 Oct 5;276(40):37459-71. Epub 2001 Jul 31. [PubMed Link Image]
  4. Alessi DR, James SR, Downes CP, Holmes AB, Gaffney PR, Reese CB, Cohen P: Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. Curr Biol. 1997 Apr 1;7(4):261-9. [PubMed Link Image]
  5. Alessi DR, Deak M, Casamayor A, Caudwell FB, Morrice N, Norman DG, Gaffney P, Reese CB, MacDougall CN, Harbison D, Ashworth A, Bownes M: 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase. Curr Biol. 1997 Oct 1;7(10):776-89. [PubMed Link Image]
  6. Stephens L, Anderson K, Stokoe D, Erdjument-Bromage H, Painter GF, Holmes AB, Gaffney PR, Reese CB, McCormick F, Tempst P, Coadwell J, Hawkins PT: Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B. Science. 1998 Jan 30;279(5351):710-4. [PubMed Link Image]
  7. Anderson KE, Coadwell J, Stephens LR, Hawkins PT: Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to activate protein kinase B. Curr Biol. 1998 Jun 4;8(12):684-91. [PubMed Link Image]
Target 2 Drug References
  1. Kulp SK, Yang YT, Hung CC, Chen KF, Lai JP, Tseng PH, Fowble JW, Ward PJ, Chen CS: 3-phosphoinositide-dependent protein kinase-1/Akt signaling represents a major cyclooxygenase-2-independent target for celecoxib in prostate cancer cells. Cancer Res. 2004 Feb 15;64(4):1444-51. [PubMed Link Image]
  2. Zhu J, Huang JW, Tseng PH, Yang YT, Fowble J, Shiau CW, Shaw YJ, Kulp SK, Chen CS: From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. Cancer Res. 2004 Jun 15;64(12):4309-18. [PubMed Link Image]
  3. Tong Z, Wu X, Ovcharenko D, Zhu J, Chen CS, Kehrer JP: Neutrophil gelatinase-associated lipocalin as a survival factor. Biochem J. 2005 Oct 15;391(Pt 2):441-8. [PubMed Link Image]
  4. Li J, Zhu J, Melvin WS, Bekaii-Saab TS, Chen CS, Muscarella P: A structurally optimized celecoxib derivative inhibits human pancreatic cancer cell growth. J Gastrointest Surg. 2006 Feb;10(2):207-14. [PubMed Link Image]
  5. Tseng PH, Wang YC, Weng SC, Weng JR, Chen CS, Brueggemeier RW, Shapiro CL, Chen CY, Dunn SE, Pollak M, Chen CS: Overcoming trastuzumab resistance in HER2-overexpressing breast cancer cells by using a novel celecoxib-derived phosphoinositide-dependent kinase-1 inhibitor. Mol Pharmacol. 2006 Nov;70(5):1534-41. Epub 2006 Aug 3. [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.