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Identification
Name Palifermin
Accession Number DB00039 (BIOD00042, BTD00042)
Type biotech
Groups approved
Description

Palifermin is a recombinant human keratinocyte growth factor (KGF). It is 140 residues long, and is produced using E. coli.
Protein structure Db00039
Display: 3D Structure
Protein chemical formula C721H1142N202O204S9
Protein average weight 16192.7000
Sequences 
>DB00039 sequence
YDYMEGGDIRVRRLFCRTQWYLRIDKRGKVKGTQEMKNNYNIMEIRTVAVGIVAIKGVES
EFYLAMNKEGKLYAKKECNEDCNFKELILENHYNTYASAKWTHNGGEMFVALNQKGIPVR
GKKTKKEQKTAHFLPMAIT

FASTA
Synonyms
FGF-7
Fibroblast growth factor- 7
HBGF-7
Keratinocyte growth factor precursor
KGF
Salts Not Available
Brand names
Name Company
Kepivance (Amgen Inc)
Brand mixtures Not Available
Categories
  • Antimucositis Agents
CAS number 162394-19-6
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For treatment of oral mucositis associated with chemotherapy and radiation therapy.
Pharmacodynamics Used in the prevention or treatment of oral mucoscitis (mouth ulcers arising from chemotherapy), Kepivance binds to the human keratinocyte growth factor (KGF) receptor on buccal cell surfaces. Kepivance acts as both a cell growth and survival factor by stimulating epithelial cell proliferation, differentiation, and migration around the tongue and mouth. The KGF receptor is found on many tissues particularly around the tongue, esophagus, salivary gland and other gastro-intestinal tract organs.
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
Volume of distribution Not Available
Protein binding Not Available
Metabolism Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intravenous
Prices
Unit description Cost Unit
Kepivance 6.25 mg vial 1650.0 USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State liquid
Experimental Properties
Property Value Source
hydrophobicity -0.650 Not Available
isoelectric point 9.47 Not Available
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
UniProt P21781 Link_out
Genbank M60828 Link_out
PharmGKB PA164744014 Link_out
Drug Product Database 2274221 Link_out
RxList http://www.rxlist.com/cgi/generic/kepivance.htm Link_out
Drugs.com http://www.drugs.com/cdi/palifermin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Palifermin Link_out
ATC Codes
  • V03AF08
AHFS Codes
  • 84:16.00
PDB Entries
FDA label show (113 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug 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

1. Fibroblast growth factor receptor 2

Pharmacological action: yes
Actions: binder

Receptor for acidic and basic fibroblast growth factors

Organism class: human
UniProt ID: P21802 Link_out
Gene: FGFR2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Neuropilin-1

Pharmacological action: unknown

The soluble isoform 2 binds VEGF-165 and appears to inhibit its binding to cells. It may also induce apoptosis by sequestering VEGF-165. May bind as well various members of the semaphorin family. Its expression has an averse effect on blood vessel number and integrity

Organism class: human
UniProt ID: O14786 Link_out
Gene: NRP1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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

3. Basic fibroblast growth factor receptor 1

Pharmacological action: unknown

Receptor for basic fibroblast growth factor. A shorter form of the receptor could be a receptor for FGF1 (aFGF)

Organism class: human
UniProt ID: P11362 Link_out
Gene: FGFR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

4. Fibroblast growth factor receptor 4

Pharmacological action: unknown

Receptor for acidic fibroblast growth factor. Does not bind to basic fibroblast growth factor. Binds FGF19

Organism class: human
UniProt ID: P22455 Link_out
Gene: FGFR4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

5. Fibroblast growth factor receptor 3

Pharmacological action: unknown

Receptor for acidic and basic fibroblast growth factors. Preferentially binds FGF1

Organism class: human
UniProt ID: P22607 Link_out
Gene: FGFR3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

6. Basement membrane-specific heparan sulfate proteoglycan core protein

Pharmacological action: unknown

This protein is an integral component of basement membranes. It is responsible for the fixed negative electrostatic charge and is involved in the charge-selective ultrafiltration properties. It serves as an attachment substrate for cells

Organism class: human
UniProt ID: P98160 Link_out
Gene: HSPG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on September 29, 2010 14:34