DT-Web

DB00039 - Palifermin


Identification
Name Palifermin
Accession Number DB00039 (BIOD00042, BTD00042)
Type biotech
Description Palifermin is a recombinant human keratinocyte growth factor (KGF). It is 140 residues long, and is produced using E. coli.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 16192.7000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For treatment of oral mucositis associated with chemotherapy and radiation therapy.
Mechanism of action Kepivance binds to the human keratinocyte growth factor (KGF) receptor found on buccal cell surfaces. The binding activates a Ras-MapK (Map kinase) signaling pathway which leads to the transcriptional activation of many proteins important for cell growth and survival.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Bendamustine Increases toxicity of bendamustine. Should not be administered within a 24 hour time period of antineoplastic agent administration.
Pralatrexate Increases the toxicity of pralatrexate. Avoid concomitant therapy or do not use palifermin within 24 hours after administration of pralatrexate.
Food Interactions Not Available

Targets


Fibroblast growth factor receptor 2
Name Fibroblast growth factor receptor 2
Gene Name FGFR2
Pharmacological action yes
Actions binder
References
  • Beaven AW, Shea TC: Recombinant human keratinocyte growth factor palifermin reduces oral mucositis and improves patient outcomes after stem cell transplant. Drugs Today (Barc). 2007 Jul;43(7):461-73. - Pubmed
  • Radtke ML, Kolesar JM: Palifermin (Kepivance) for the treatment of oral mucositis in patients with hematologic malignancies requiring hematopoietic stem cell support. J Oncol Pharm Pract. 2005 Sep;11(3):121-5. - Pubmed
  • Huang YW, Wang LS, Chang HL, Ye W, Shu S, Sugimoto Y, Lin YC: Effect of keratinocyte growth factor on cell viability in primary cultured human prostate cancer stromal cells. J Steroid Biochem Mol Biol. 2006 Jul;100(1-3):24-33. Epub 2006 Jul 18. - Pubmed
  • Patrie KM, Kudla AJ, Olwin BB, Chiu IM: Conservation of ligand specificity between the mammalian and amphibian fibroblast growth factor receptors. J Biol Chem. 1995 Dec 1;270(48):29018-24. - Pubmed
  • Cardoso WV, Itoh A, Nogawa H, Mason I, Brody JS: FGF-1 and FGF-7 induce distinct patterns of growth and differentiation in embryonic lung epithelium. Dev Dyn. 1997 Mar;208(3):398-405. - Pubmed
  • Berman B, Ostrovsky O, Shlissel M, Lang T, Regan D, Vlodavsky I, Ishai-Michaeli R, Ron D: Similarities and differences between the effects of heparin and glypican-1 on the bioactivity of acidic fibroblast growth factor and the keratinocyte growth factor. J Biol Chem. 1999 Dec 17;274(51):36132-8. - Pubmed
  • Zhu X, Lee K, Asa SL, Ezzat S: Epigenetic silencing through DNA and histone methylation of fibroblast growth factor receptor 2 in neoplastic pituitary cells. Am J Pathol. 2007 May;170(5):1618-28. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.3074
Neuropilin-1
Name Neuropilin-1
Gene Name NRP1
Pharmacological action unknown
Actions Not Available
References
  • Beer HD, Vindevoghel L, Gait MJ, Revest JM, Duan DR, Mason I, Dickson C, Werner S: Fibroblast growth factor (FGF) receptor 1-IIIb is a naturally occurring functional receptor for FGFs that is preferentially expressed in the skin and the brain. J Biol Chem. 2000 May 26;275(21):16091-7. - Pubmed
  • Friedl A, Chang Z, Tierney A, Rapraeger AC: Differential binding of fibroblast growth factor-2 and -7 to basement membrane heparan sulfate: comparison of normal and abnormal human tissues. Am J Pathol. 1997 Apr;150(4):1443-55. - Pubmed
  • Wang F, Lu W, McKeehan K, Mohamedali K, Gabriel JL, Kan M, McKeehan WL: Common and specific determinants for fibroblast growth factors in the ectodomain of the receptor kinase complex. Biochemistry. 1999 Jan 5;38(1):160-71. - Pubmed
DTHybrid score 1.7634
Basic fibroblast growth factor receptor 1
Name Basic fibroblast growth factor receptor 1
Gene Name FGFR1
Pharmacological action unknown
Actions Not Available
References
  • Ostrovsky O, Berman B, Gallagher J, Mulloy B, Fernig DG, Delehedde M, Ron D: Differential effects of heparin saccharides on the formation of specific fibroblast growth factor (FGF) and FGF receptor complexes. J Biol Chem. 2002 Jan 25;277(4):2444-53. Epub 2001 Nov 19. - Pubmed
  • Sher I, Lang T, Lubinsky-Mink S, Kuhn J, Adir N, Chatterjee S, Schomburg D, Ron D: Identification of residues important both for primary receptor binding and specificity in fibroblast growth factor-7. J Biol Chem. 2000 Nov 10;275(45):34881-6. - Pubmed
  • Matsubara A, Yasumoto H, Usui T: Hormone Refractory Prostate Cancer and Fibroblast Growth Factor Receptor. Breast Cancer. 1999 Oct 25;6(4):320-324. - Pubmed
  • Lu W, Luo Y, Kan M, McKeehan WL: Fibroblast growth factor-10. A second candidate stromal to epithelial cell andromedin in prostate. J Biol Chem. 1999 Apr 30;274(18):12827-34. - Pubmed
  • Wang F, Lu W, McKeehan K, Mohamedali K, Gabriel JL, Kan M, McKeehan WL: Common and specific determinants for fibroblast growth factors in the ectodomain of the receptor kinase complex. Biochemistry. 1999 Jan 5;38(1):160-71. - Pubmed
DTHybrid score 1.6403
Fibroblast growth factor receptor 4
Name Fibroblast growth factor receptor 4
Gene Name FGFR4
Pharmacological action unknown
Actions Not Available
References
  • Imagawa W, Cunha GR, Young P, Nandi S: Keratinocyte growth factor and acidic fibroblast growth factor are mitogens for primary cultures of mammary epithelium. Biochem Biophys Res Commun. 1994 Nov 15;204(3):1165-9. - Pubmed
  • Sher I, Lang T, Lubinsky-Mink S, Kuhn J, Adir N, Chatterjee S, Schomburg D, Ron D: Identification of residues important both for primary receptor binding and specificity in fibroblast growth factor-7. J Biol Chem. 2000 Nov 10;275(45):34881-6. - Pubmed
  • Sannes PL, Khosla J, Li CM, Pagan I: Sulfation of extracellular matrices modifies growth factor effects on type II cells on laminin substrata. Am J Physiol. 1998 Oct;275(4 Pt 1):L701-8. - Pubmed
  • Luo Y, Lu W, Mohamedali KA, Jang JH, Jones RB, Gabriel JL, Kan M, McKeehan WL: The glycine box: a determinant of specificity for fibroblast growth factor. Biochemistry. 1998 Nov 24;37(47):16506-15. - Pubmed
  • Yamanaka T, Sakamoto A, Tanaka Y, Zhang Y, Hayashido Y, Toratani S, Akagawa Y, Okamoto T: Isolation and serum-free culture of epithelial cells derived from epithelial rests of Malassez in human periodontal ligament. In Vitro Cell Dev Biol Anim. 2000 Sep;36(8):548-53. - Pubmed
DTHybrid score 0.8758
Fibroblast growth factor receptor 3
Name Fibroblast growth factor receptor 3
Gene Name FGFR3
Pharmacological action unknown
Actions Not Available
References
  • Cancilla B, Davies A, Cauchi JA, Risbridger GP, Bertram JF: Fibroblast growth factor receptors and their ligands in the adult rat kidney. Kidney Int. 2001 Jul;60(1):147-55. - Pubmed
  • Yamanaka T, Sakamoto A, Tanaka Y, Zhang Y, Hayashido Y, Toratani S, Akagawa Y, Okamoto T: Isolation and serum-free culture of epithelial cells derived from epithelial rests of Malassez in human periodontal ligament. In Vitro Cell Dev Biol Anim. 2000 Sep;36(8):548-53. - Pubmed
  • Beer HD, Vindevoghel L, Gait MJ, Revest JM, Duan DR, Mason I, Dickson C, Werner S: Fibroblast growth factor (FGF) receptor 1-IIIb is a naturally occurring functional receptor for FGFs that is preferentially expressed in the skin and the brain. J Biol Chem. 2000 May 26;275(21):16091-7. - Pubmed
  • Launay C, Fromentoux V, Thery C, Shi DL, Boucaut JC: Comparative analysis of the tissue distribution of three fibroblast growth factor receptor mRNAs during amphibian morphogenesis. Differentiation. 1994 Dec;58(2):101-11. - Pubmed
  • Mummery CL, van Rooyen M, Bracke M, van den Eijnden-van Raaij J, van Zoelen EJ, Alitalo K: Fibroblast growth factor-mediated growth regulation and receptor expression in embryonal carcinoma and embryonic stem cells and human germ cell tumours. Biochem Biophys Res Commun. 1993 Feb 26;191(1):188-95. - Pubmed
DTHybrid score 0.8421
Basement membrane-specific heparan sulfate proteoglycan core protein
Name Basement membrane-specific heparan sulfate proteoglycan core protein
Gene Name HSPG2
Pharmacological action unknown
Actions Not Available
References
  • Berman B, Ostrovsky O, Shlissel M, Lang T, Regan D, Vlodavsky I, Ishai-Michaeli R, Ron D: Similarities and differences between the effects of heparin and glypican-1 on the bioactivity of acidic fibroblast growth factor and the keratinocyte growth factor. J Biol Chem. 1999 Dec 17;274(51):36132-8. - Pubmed
  • Sharma B, Handler M, Eichstetter I, Whitelock JM, Nugent MA, Iozzo RV: Antisense targeting of perlecan blocks tumor growth and angiogenesis in vivo. J Clin Invest. 1998 Oct 15;102(8):1599-608. - Pubmed
  • Iwabuchi T, Goetinck PF: Syndecan-4 dependent FGF stimulation of mouse vibrissae growth. Mech Dev. 2006 Nov;123(11):831-41. Epub 2006 Aug 12. - Pubmed
  • Asada N, Tanaka Y, Hayashido Y, Toratani S, Kan M, Kitamoto M, Nakanishi T, Kajiyama G, Chayama K, Okamoto T: Expression of fibroblast growth factor receptor genes in human hepatoma-derived cell lines. In Vitro Cell Dev Biol Anim. 2003 Jul-Aug;39(7):321-8. - Pubmed
DTHybrid score 0.898

Predictions


Id Partner name Gene Name Score
950 Alpha platelet-derived growth factor receptor PDGFRA 0.1186
504 Mast/stem cell growth factor receptor KIT 0.1123
5787 Angiopoietin-1 receptor TEK 0.1069
407 Vascular endothelial growth factor receptor 2 KDR 0.1063
4177 Proto-oncogene tyrosine-protein kinase receptor ret RET 0.1047
6824 Tyrosine-protein kinase Lyn LYN 0.0909
165 FL cytokine receptor FLT3 0.0869
17 Proto-oncogene tyrosine-protein kinase ABL1 ABL1 0.079
937 Proto-oncogene tyrosine-protein kinase LCK LCK 0.0666
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.065
4924 Cytochrome P450 2C8 CYP2C8 0.0544
26 Vascular endothelial growth factor receptor 3 FLT4 0.0543
32 Vascular endothelial growth factor receptor 1 FLT1 0.0531
933 Proto-oncogene tyrosine-protein kinase Src SRC 0.0528
1588 Multidrug resistance protein 1 ABCB1 0.0502
228 Beta platelet-derived growth factor receptor PDGFRB 0.048
4118 Cytochrome P450 3A5 CYP3A5 0.045
776 Bile salt export pump ABCB11 0.0446
4512 Cytochrome P450 3A4 CYP3A4 0.0441
4119 Cytochrome P450 2D6 CYP2D6 0.0423
2450 Tyrosine-protein kinase ITK/TSK ITK 0.0362
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0315
40 RAF proto-oncogene serine/threonine-protein kinase RAF1 0.0303
5798 Mitogen-activated protein kinase 11 MAPK11 0.0282
698 B-Raf proto-oncogene serine/threonine-protein kinase BRAF 0.0264
760 Fibroblast growth factor 1 FGF1 0.0253
1787 Nuclear factor NF-kappa-B p105 subunit NFKB1 0.0243
4200 Cytochrome P450 1A2 CYP1A2 0.0229
936 Ephrin type-A receptor 2 EPHA2 0.0203
6016 Cytochrome P450 2C19 CYP2C19 0.0194
777 Tumor necrosis factor TNF 0.0191
1618 High affinity nerve growth factor receptor NTRK1 0.0186
4757 Cytochrome P450 2C9 CYP2C9 0.0186
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0163
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0148
290 Prostaglandin G/H synthase 2 PTGS2 0.0118
6030 Cytochrome P450 2B6 CYP2B6 0.0118
20 Prostaglandin G/H synthase 1 PTGS1 0.0112
6024 Cytochrome P450 1A1 CYP1A1 0.0107
6013 Cytochrome P450 2E1 CYP2E1 0.0103
2164 Multidrug resistance-associated protein 4 ABCC4 0.0044
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0039
6107 Cytochrome P450 3A7 CYP3A7 0.0034
↑