Becaplermin

Identification

Name
Becaplermin
Accession Number
DB00102  (BTD00053, BIOD00053)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Other protein based therapies
Description

Becaplermin is produced by recombinant DNA technology by insertion of the gene for the B chain of platelet derived growth factor (PDGF) into the yeast, Saccharomyces cerevisiae. Becaplermin has a molecular weight of approximately 25 KD and is a homodimer composed of two identical polypeptide chains that are bound together by disulfide bonds.

Protein structure
Db00102
Protein chemical formula
C532H892N162O153S9
Protein average weight
12294.4 Da
Sequences
>DB00102 sequence
SLGSLTIAEPAMIAECKTRTEVFEISRRLIDRTNANFLVWPPCVEVQRCSGCCNNRNVQC
RPTQVQLRPVQVRKIEIVRKKPIFKKATVTLEDHLACKCETVAAARPVT
Download FASTA Format
Synonyms
  • c-sis
  • PDGF B-chain
  • PDGF-2
  • PDGF-BB
  • PDGFB
  • Platelet-derived growth factor B chain precursor
  • Platelet-derived growth factor beta polypeptide
  • SH-POLYPEPTIDE-59
External IDs
RWJ-60235
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RegranexGel100 ug/1gTopicalSmith & Nephew, Inc.2011-11-01Not applicableUs
RegranexGel100 ug/1gTopicalHealthpoint2011-11-012016-01-31Us
RegranexGel100 ug/1gTopicalOrtho-McNeil-Janssen Pharmaceuticals, Inc.1998-02-012013-01-31Us
Regranex (becaplermin) 0.01%Gel100 mcgTopicalJanssen Pharmaceuticals1999-02-012011-07-27Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
RegranexBecaplermin (0.01 %)GelCutaneousJanssen Cilag International Nv1999-03-292012-08-15Eu
Categories
UNII
1B56C968OA
CAS number
165101-51-9

Pharmacology

Indication

For topical treatment of skin ulcers (from diabetes)

Associated Conditions
Pharmacodynamics

Used for the topical treatment of skin ulcers, Regranex has a biological activity similar to that of endogenous platelet-derived growth factor, which includes promoting the chemotactic recruitment and proliferation of cells involved in wound repair and enhancing the formation of granulation tissue.

Mechanism of action

Binds to the beta platelet-derived growth factor (PDGF) receptor, a tyrosine kinase receptor. PDGF is known to exist as a dimer, and activates its signaling pathway by a ligand induced receptor dimerization and autophosphorylation. PDGF receptors also contain many auto-phosphorylation sites, which serve to mediate binding of SH2 sites and subsequently signal corresponding pathways. There are five different isoforms of PDGF that activate through two different receptors (alpha and beta).

TargetActionsOrganism
APlatelet-derived growth factor receptor betaNot AvailableHuman
UPlatelet-derived growth factor receptor alphaNot AvailableHuman
UAlpha-2-macroglobulinNot AvailableHuman
Absorption

very little systemic absorption. 15% of patients experienced complete healing within 8 weeks, while for 25% of patients, it was at 10 weeks.

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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

General References
  1. Link [Link]
  2. Link [Link]
External Links
UniProt
P01127
Genbank
K01401
PubChem Substance
46508246
ChEMBL
CHEMBL1201556
Therapeutic Targets Database
DAP000028
PharmGKB
PA164749511
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Becaplermin
ATC Codes
A01AD08 — BecaplerminD03AX06 — Becaplermin
FDA label
Download (248 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1WithdrawnTreatmentDiabetic Ulcers1
1, 2CompletedTreatmentDiabetic Foot Ulcers (DFU)1
3CompletedTreatmentHypertensive Leg Ulcer / Martorell's ulcer / Necrotic Angiodermatitis1
3Not Yet RecruitingTreatmentFoot Ulcer, Diabetic / Venous Ulcers1
3TerminatedTreatmentDiabetic Foot / Diabetic Neuropathies / Skin Ulcers / Ulcus Cruris1
Not AvailableCompletedNot AvailableDiabetes Mellitus (DM)1
Not AvailableUnknown StatusTreatmentDiabetic Foot Ulcers (DFU)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Janssen-Ortho Inc.
  • McNeil Laboratories
  • OMJ Pharmaceuticals
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Ortho-McNeil-Janssen Pharmaceuticals Inc.
Dosage forms
FormRouteStrength
GelCutaneous0.01 %
GelTopical100 ug/1g
GelTopical100 mcg
Prices
Unit descriptionCostUnit
Regranex 0.01% Gel 15 gm Tube723.82USD tube
Regranex 0.01% gel46.4USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1340846No1999-12-072015-12-15Canada

Properties

State
Liquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.160Not Available
isoelectric point9.38Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Vascular endothelial growth factor binding
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
Molecular Weight
123966.895 Da
References
  1. Papanas N, Maltezos E: Becaplermin gel in the treatment of diabetic neuropathic foot ulcers. Clin Interv Aging. 2008;3(2):233-40. [PubMed:18686746]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chem...
Gene Name
PDGFRA
Uniprot ID
P16234
Uniprot Name
Platelet-derived growth factor receptor alpha
Molecular Weight
122668.46 Da
References
  1. Abdiu A, Walz TM, Nishikawa BK, Wingren S, Larsson SE, Wasteson A: Human malignant fibrous histiocytomas in vitro: growth characteristics and their association with expression of mRNA for platelet-derived growth factor, transforming growth factor-alpha and their receptors. Eur J Cancer. 1998 Dec;34(13):2094-100. [PubMed:10070317]
  2. Ebert M, Yokoyama M, Friess H, Kobrin MS, Buchler MW, Korc M: Induction of platelet-derived growth factor A and B chains and over-expression of their receptors in human pancreatic cancer. Int J Cancer. 1995 Sep 4;62(5):529-35. [PubMed:7665222]
  3. Miller-Kasprzak E, Niemir ZI, Czekalski S: [Structure and function of PDGF-R-alpha and its expression in normal kidney and kidney diseases]. Przegl Lek. 2002;59(10):826-31. [PubMed:12632922]
  4. Heidaran MA, Pierce JH, Lombardi D, Ruggiero M, Gutkind JS, Matsui T, Aaronson SA: Deletion or substitution within the alpha platelet-derived growth factor receptor kinase insert domain: effects on functional coupling with intracellular signaling pathways. Mol Cell Biol. 1991 Jan;11(1):134-42. [PubMed:1702511]
  5. Yu J, Liu XW, Kim HR: Platelet-derived growth factor (PDGF) receptor-alpha-activated c-Jun NH2-terminal kinase-1 is critical for PDGF-induced p21WAF1/CIP1 promoter activity independent of p53. J Biol Chem. 2003 Dec 5;278(49):49582-8. Epub 2003 Sep 23. [PubMed:14506245]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Tumor necrosis factor binding
Specific Function
Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for differen...
Gene Name
A2M
Uniprot ID
P01023
Uniprot Name
Alpha-2-macroglobulin
Molecular Weight
163289.945 Da
References
  1. Lizonova A, Bizik J, Grofova M, Vaheri A: Coexpression of tumor-associated alpha 2-macroglobulin and growth factors in human melanoma cell lines. J Cell Biochem. 1990 Aug;43(4):315-25. [PubMed:1697862]
  2. Bonner JC, Osornio-Vargas AR: Differential binding and regulation of platelet-derived growth factor A and B chain isoforms by alpha 2-macroglobulin. J Biol Chem. 1995 Jul 7;270(27):16236-42. [PubMed:7541796]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:37