Collagenase clostridium histolyticum

Identification

Name
Collagenase clostridium histolyticum
Accession Number
DB00048  (BTD00010, BIOD00010, DB11249)
Type
Biotech
Groups
Approved, Investigational
Description

Collagenase clostridium histolyticum is an enzyme produced by the bacterium Clostridium histolyticum that dismantles collagen. It is used as a powder-and-solvent injection kit for the treatment of Dupuytren's contracture, a condition where the fingers bend towards the palm and cannot be fully straightened, and Peyronie's disease, a connective tissue disorder involving the growth of fibrous plaques in the soft tissue of the penis. BioSpecifics Technologies developed the preparation, which is manufactured and marketed by Auxilium Pharmaceuticals as Xiaflex in the US and by Sobi as Xiapex in Europe.

Protein structure
Db00048
Protein chemical formula
C5028H7666N1300O1564S21
Protein average weight
112023.2 Da
Sequences
> Collagenase Sequence 
MKRKCLSKRLMLAITMATIFTVNSTLPIYAAVDKNNATAAVQNESKRYTVSYLKTLNYYD
LVDLLVKTEIENLPDLFQYSSDAKEFYGNKTRMSFIMDEIGRRAPQYTEIDHKGIPTLVE
VVRAGFYLGFHNKELNEINKRSFKERVIPSILAIQKNPNFKLGTEVQDKIVSATGLLAGN
ETAPPEVVNNFTPILQDCIKNIDRYALDDLKSKALFNVLAAPTYDITEYLRATKEKPENT
PWYGKIDGFINELKKLALYGKINDNNSWIIDNGIYHIAPLGKLHSNNKIGIETLTEVMKV
YPYLSMQHLQSADQIKRHYDSKDAEGNKIPLDKFKKEGKEKYCPKTYTFDDGKVIIKAGA
RVEEEKVKRLYWASKEVNSQFFRVYGIDKPLEEGNPDDILTMVIYNSPEEYKLNSVLYGY
DTNNGGMYIEPEGTFFTYEREAQESTYTLEELFRHEYTHYLQGRYAVPGQWGRTKLYDND
RLTWYEEGGAELFAGSTRTSGILPRKSIVSNIHNTTRNNRYKLSDTVHSKYGASFEFYNY
ACMFMDYMYNKDMGILNKLNDLAKNNDVDGYDNYIRDLSSNYALNDKYQDHMQERIDNYE
NLTVPFVADDYLVRHAYKNPNEIYSEISEVAKLKDAKSEVKKSQYFSTFTLRGSYTGGAS
KGKLEDQKAMNKFIDDSLKKLDTYSWSGYKTLTAYFTNYKVDSSNRVTYDVVFHGYLPNE
GDSKNSLPYGKINGTYKGTEKEKIKFSSEGSFDPDGKIVSYEWDFGDGNKSNEENPEHSY
DKVGTYTVKLKVTDDKGESSVSTTTAEIKDLSENKLPVIYMHVPKSGALNQKVVFYGKGT
YDPDGSIAGYQWDFGDGSDFSSEQNPSHVYTKKGEYTVTLRVMDSSGQMSEKTMKIKITD
PVYPIGTEKEPNNSKETASGPIVPGIPVSGTIENTSDQDYFYFDVITPGEVKIDINKLGY
GGATWVVYDENNNAVSYATDDGQNLSGKFKADKPGRYYIHLYMFNGSYMPYRINIEGSVG
R
Download FASTA Format
Synonyms
  • Clostridium histolyticum enzymes
  • Collagenase
External IDs
AA-4500 / AA4500 / PF-5076985
Product Ingredients
Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Collagenase SantylOintment250 [arb'U]/gTopicalHealthpoint2006-10-182017-06-30Us
Collagenase SantylOintment250 [arb'U]/gTopicalSmith & Nephew, Inc.2006-10-18Not applicableUs
SantylOintment250 unitTopicalSmith & Nephew, Inc.1994-12-31Not applicableCanada
XiaflexPowder, for solution0.9 mgIntralesionalEndo Ventures Ltd2012-11-14Not applicableCanada
XiaflexKitEndo Pharmaceuticals2010-02-22Not applicableUs
XiapexInjection, powder, for solution0.9 mgIntralesionalSwedish Orphan Biovitrum Ab2011-02-28Not applicableEu
Approved Generic Prescription Products
Not Available
Approved Over the Counter Products
Not Available
Unapproved/Other Products
Not Available
International/Other Brands
Cordase / Santyl (Advance Biofactures Corp) / Xiapex (Sobi)
Brand mixtures
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Kimchi Vitamin chewable multivitaminTablet, chewableOralTobico2010-03-18Not applicableUs
Categories
UNII
9X7O8V25IT
CAS number
9001-12-1

Pharmacology

Indication

Used to promote debridement of necrotic tissue in the treatment of severe burns and dermal ulcers including decubitus ulcers.

Structured Indications
Pharmacodynamics

Used in the treatment of skin ulcers and sever burns, collagenase is able to digest collagen in necrotic tissue at physiological pH by hydrolyzing the peptide bonds of undenatured and denatured collagen. Collagenase thus contributes towards the formation of granulation tissue and subsequent epithelization of dermal ulcers and severely burned areas. The action of collagenase may remove substrates necessary for bacterial proliferation or may permit antibodies, leukocytes, and antibiotics better access to the infected area.

Mechanism of action

Collagenase is a protease that is specific to collagen. The triple helical region of interstitial collagens is highly resistant to most cell proteinases. However, during remodeling of the connective tissue in such processes as wound healing and metastasis, collagen becomes susceptible to cleavage by collagenases. Collagenase cleaves all 3 alpha helical chains of native Types I, II and III collagens at a single locus by hydrolyzing the peptide bond following the Gly residue of the sequence: Gly 775-(Ile or Leu) 776-(Ala or Leu) 777 located approximately three-fourths of the chain length from each N-terminus

TargetActionsOrganism
UCollagen alpha-1(I) chainNot AvailableHuman
UCollagen alpha-1(II) chainNot AvailableHuman
UCollagen alpha-1(III) chainNot AvailableHuman
UCollagen alpha-2(I) chainNot AvailableHuman
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

Synthesis Reference

Hun-Chi Lin, Shau-Ping Lei, "Molecular cloning of the genes responsible for collagenase production from Clostridium histolyticum." U.S. Patent US5177017, issued December, 1972.

US5177017
General References
  1. Norris DB, Trudgill PW: Multiple forms of cyclohexanone oxygenase from Nocardia globerula CL1. Eur J Biochem. 1976 Mar 16;63(1):193-8. [PubMed:4312 ]
  2. Pajot P: Fluroescence of proteins in 6-M guanidine hydrochloride. A method for the quantitative determination of tryptophan. Eur J Biochem. 1976 Mar 16;63(1):263-9. [PubMed:4317 ]
External Links
KEGG Compound
C00816
Therapeutic Targets Database
DAP000965
PharmGKB
PA449107
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Collagenase
ATC Codes
M09AB02 — Collagenase clostridium histolyticumD03BA52 — Collagenase, combinationsD03BA02 — Collagenase
AHFS Codes
  • 84:92.00
PDB Entries
FDA label
Not Available
MSDS
Download (72.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableDupuytren's Contracture1
1CompletedTreatmentCellulite / Edematous Fibrosclerotic Panniculopathy (EFP)1
1CompletedTreatmentChronic Total Occlusion (CTO)1
1CompletedTreatmentDiabetic Foot / Ulcus Cruris1
1RecruitingTreatmentLeiomyomas / Uterine Leiomyomas1
1, 2CompletedTreatmentAdhesion of Flexor Tendon of Hand1
2CompletedTreatmentAdhesive Capsulitis / Adhesive Capsulitis of Shoulder2
2CompletedTreatmentCellulite / Edematous Fibrosclerotic Panniculopathy (EFP)1
2CompletedTreatmentChronic Coronary Total Occlusions1
2CompletedTreatmentDupuytren's Contracture1
2CompletedTreatmentDupuytren's Disease1
2CompletedTreatmentEdematous Fibrosclerotic Panniculopathy (EFP)1
2CompletedTreatmentLipomas2
2CompletedTreatmentPeyronie's Disease2
2Enrolling by InvitationTreatmentCellulite / Edematous Fibrosclerotic Panniculopathy (EFP)1
2Not Yet RecruitingTreatmentUrethral Strictures1
2Unknown StatusTreatmentBurn's Associated Contracture1
2Unknown StatusTreatmentCellulite1
2WithdrawnTreatmentAdhesive Capsulitis / Adhesive Capsulitis of Shoulder1
2, 3SuspendedTreatmentUlcers1
3CompletedTreatmentAdvanced Dupuytren's Disease3
3CompletedTreatmentDupuytren's Contracture6
3CompletedTreatmentDupuytren's Disease1
3CompletedTreatmentPeyronie's Disease5
3WithdrawnTreatmentPressure Ulcers1
4Active Not RecruitingTreatmentDupuytren's Contracture1
4CompletedNot AvailableDupuytren's Contracture1
4CompletedBasic ScienceImpaired Wound Healing / Scarring1
4CompletedDiagnosticDiabetic Foot Ulcers (DFU)1
4CompletedTreatmentDiabetic Foot Ulcers (DFU)1
4CompletedTreatmentDiabetic Foot Ulcers (DFU) / Diabetic Foot Wounds3
4CompletedTreatmentDiabetic Foot Ulcers (DFU) / Foot Wounds1
4CompletedTreatmentDiabetic Foot / Foot Ulcer, Diabetic1
4CompletedTreatmentDupuytren's Contracture1
4CompletedTreatmentDupuytren's Disease2
4RecruitingTreatmentDupuytren's Contracture / Dupuytren's Disease of Finger1
4RecruitingTreatmentDupuytrens Contracture1
4RecruitingTreatmentPartial Thickness Burn1
4TerminatedTreatmentPressure Ulcers1
4WithdrawnTreatmentFoot Ulcer, Diabetic / Pressure Ulcers1
4WithdrawnTreatmentPartial Thickness Burn1
Not AvailableCompletedNot AvailableFollow up to Acute Wound Scar Study1
Not AvailableCompletedTreatmentDupuytrens Contracture1
Not AvailableRecruitingNot AvailableDupuytren's Disease1
Not AvailableTerminatedTreatmentUlcers / Wounds1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
OintmentTopical250 [arb'U]/g
Tablet, chewableOral
OintmentTopical250 unit
Kit
Powder, for solutionIntralesional0.9 mg
Injection, powder, for solutionIntralesional0.9 mg
Prices
Unit descriptionCostUnit
Xiaflex 0.9 mg vial3900.0USD vial
Collagenase powder2432.7USD g
Santyl 250 unit/gm Ointment 15 gm Tube62.98USD tube
Santyl ointment4.13USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.714Not Available
isoelectric point5.58Not 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
Unknown
General Function
Platelet-derived growth factor binding
Specific Function
Type I collagen is a member of group I collagen (fibrillar forming collagen).
Gene Name
COL1A1
Uniprot ID
P02452
Uniprot Name
Collagen alpha-1(I) chain
Molecular Weight
138941.105 Da
References
  1. Egeblad M, Shen HC, Behonick DJ, Wilmes L, Eichten A, Korets LV, Kheradmand F, Werb Z, Coussens LM: Type I collagen is a genetic modifier of matrix metalloproteinase 2 in murine skeletal development. Dev Dyn. 2007 Jun;236(6):1683-93. [PubMed:17440987 ]
  2. Lindsey ML, Yoshioka J, MacGillivray C, Muangman S, Gannon J, Verghese A, Aikawa M, Libby P, Krane SM, Lee RT: Effect of a cleavage-resistant collagen mutation on left ventricular remodeling. Circ Res. 2003 Aug 8;93(3):238-45. Epub 2003 Jul 10. [PubMed:12855673 ]
  3. Beare AH, O'Kane S, Krane SM, Ferguson MW: Severely impaired wound healing in the collagenase-resistant mouse. J Invest Dermatol. 2003 Jan;120(1):153-63. [PubMed:12535212 ]
  4. Chiu CJ, Chang ML, Chiang CP, Hahn LJ, Hsieh LL, Chen CJ: Interaction of collagen-related genes and susceptibility to betel quid-induced oral submucous fibrosis. Cancer Epidemiol Biomarkers Prev. 2002 Jul;11(7):646-53. [PubMed:12101112 ]
  5. Beare AH, Krane SM, Ferguson MW: Variable impairment of wound healing in the heterozygous collagenase-resistant mouse. Wound Repair Regen. 2005 Jan-Feb;13(1):27-40. [PubMed:15659034 ]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Platelet-derived growth factor binding
Specific Function
Type II collagen is specific for cartilaginous tissues. It is essential for the normal embryonic development of the skeleton, for linear growth and for the ability of cartilage to resist compressiv...
Gene Name
COL2A1
Uniprot ID
P02458
Uniprot Name
Collagen alpha-1(II) chain
Molecular Weight
141785.08 Da
References
  1. Fraser A, Fearon U, Billinghurst RC, Ionescu M, Reece R, Barwick T, Emery P, Poole AR, Veale DJ: Turnover of type II collagen and aggrecan in cartilage matrix at the onset of inflammatory arthritis in humans: relationship to mediators of systemic and local inflammation. Arthritis Rheum. 2003 Nov;48(11):3085-95. [PubMed:14613270 ]
  2. Imai K, Dalal SS, Hambor J, Mitchell P, Okada Y, Horton WC, D'Armiento J: Bone growth retardation in mouse embryos expressing human collagenase 1. Am J Physiol Cell Physiol. 2007 Oct;293(4):C1209-15. Epub 2007 Jul 25. [PubMed:17652426 ]
  3. Verstappen SM, Poole AR, Ionescu M, King LE, Abrahamowicz M, Hofman DM, Bijlsma JW, Lafeber FP: Radiographic joint damage in rheumatoid arthritis is associated with differences in cartilage turnover and can be predicted by serum biomarkers: an evaluation from 1 to 4 years after diagnosis. Arthritis Res Ther. 2006;8(1):R31. Epub 2006 Jan 10. [PubMed:16507130 ]
  4. Martin G, Bogdanowicz P, Domagala F, Ficheux H, Pujol JP: Articular chondrocytes cultured in hypoxia: their response to interleukin-1beta and rhein, the active metabolite of diacerhein. Biorheology. 2004;41(3-4):549-61. [PubMed:15299286 ]
  5. Pratta MA, Yao W, Decicco C, Tortorella MD, Liu RQ, Copeland RA, Magolda R, Newton RC, Trzaskos JM, Arner EC: Aggrecan protects cartilage collagen from proteolytic cleavage. J Biol Chem. 2003 Nov 14;278(46):45539-45. Epub 2003 Jul 30. [PubMed:12890681 ]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Platelet-derived growth factor binding
Specific Function
Collagen type III occurs in most soft connective tissues along with type I collagen. Involved in regulation of cortical development. Is the major ligand of GPR56 in the developing brain and binding...
Gene Name
COL3A1
Uniprot ID
P02461
Uniprot Name
Collagen alpha-1(III) chain
Molecular Weight
138564.005 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Cole WG, Chiodo AA, Lamande SR, Janeczko R, Ramirez F, Dahl HH, Chan D, Bateman JF: A base substitution at a splice site in the COL3A1 gene causes exon skipping and generates abnormal type III procollagen in a patient with Ehlers-Danlos syndrome type IV. J Biol Chem. 1990 Oct 5;265(28):17070-7. [PubMed:2145268 ]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein binding, bridging
Specific Function
Type I collagen is a member of group I collagen (fibrillar forming collagen).
Gene Name
COL1A2
Uniprot ID
P08123
Uniprot Name
Collagen alpha-2(I) chain
Molecular Weight
129313.615 Da
References
  1. Chiu CJ, Chang ML, Chiang CP, Hahn LJ, Hsieh LL, Chen CJ: Interaction of collagen-related genes and susceptibility to betel quid-induced oral submucous fibrosis. Cancer Epidemiol Biomarkers Prev. 2002 Jul;11(7):646-53. [PubMed:12101112 ]
Drug created on June 13, 2005 07:24 / Updated on June 07, 2017 15:30