Collagenase clostridium histolyticum

Identification

Name
Collagenase clostridium histolyticum
Accession Number
DB00048
Description

Collagenase clostridium histolyticum is an enzyme produced by the bacterium Clostridium histolyticum. It is beneficial in the breakdown of collagen plaques for the treatment of Dupuytren's contracture and Peyronie's disease.11 The topical formulation is used for the debridement of necrotic tissue due to burns or chronic ulcers.14

On July 6, 2020 a combination of injectable bacterial collagenases was approved by the FDA for the treatment of cellulite in adult women.10 Also known as Qwo, this injection is the first approved injectable treatment for cellulite and was developed by Endo International.13

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Other protein based therapies
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
  • Collagenase clostridium histolyticum
  • collagenase clostridium histolyticum-aaes
External IDs
  • AA-4500
  • AA4500
  • PF-5076985

Pharmacology

Indication

Collagenase clostridium histolyticum is indicated for the treatment of adults with Dupuytren's contracture with a palpable cord. Additionally, it is used to treat men with Peyronie's disease diagnosed with a penile curvature deformity of at least a 30-degree angle at the beginning of therapy in addition to palpable plaques.11 Collagenase ointment is used for the tissue debridement of chronic dermal ulcers and severely burned tissues.15 The combination collagenase product, also known as Qwo, is used for the treatment of moderate to severe cellulite in the buttocks of adult women.10

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Collagenase digests collagen, treating conditions such as Peyronie's disease, cellulite, chronic ulcers, burns, and contractures.10,11,14

Mechanism of action

Peyronie's disease is a fibrous lesion of the tunica albuginea in the penile tissues.4 Cellulite is a multifactorial condition resulting in the accumulation of fibrotic dermal septae and the expansion of subcutaneous fat.3 Dupuytren's contracture is a fibroproliferative disease that results in the fibrous deposition of collagen in the hands, limiting mobility and functionality of the hands.5 The collagen deposition in the abovementioned conditions is the target of collagenase enzyme therapy.6,7

These enzymes are proteinases acting to hydrolyze collagen's triple-helical conformation, resulting in the lysis of collagen deposits and relief from the necrotic tissue and plaques associated with several conditions.11,14 On a molecular level, collagenases cleave polypeptide chains that make up the collagen triple helix structure at various loci, leading to solubilization from the collagen fibril.8

TargetActionsOrganism
ACollagen alpha-1(I) chain
binder
Humans
ACollagen alpha-1(II) chain
binder
Humans
ACollagen alpha-1(III) chain
binder
Humans
Absorption

There is currently limited readily available regarding the absorption of collagenase through the skin.14 In a pharmacokinetic study, the serum concentrations of clostridium type I collagenase (AUX-I) and clostridium type II collagenase (AUX-II) were measured. Both were detected under the lower limit of quantitation of 5 ng/mL and 25 ng/mL, respectively, in volunteers administered one dose of the collagenase histolyticum combination product, Qwo, at a dose of up to 3.36 mg in a maximum of 4 body areas.10

Volume of distribution

There is no currently available information regarding the presence of collagenase in body fluids or uptake by particular organs and passage through the blood-brain barrier.14 Systemic pharmacokinetic studies evaluation volume of distribution have not been performed, however, collagenase histolyticum is likely to have local degradative effects in the region of the application without effects on the vasculature and elastic tissue.9

Protein binding

There is no readily available information regarding the protein binding of collagenase.14

Metabolism

No formal systemic metabolism studies have been performed with collagenase histolyticum.9

Route of elimination
Not Available
Half-life
Not Available
Clearance

Clearance information for collagenase is not readily available.14

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

No clinical reaction has been attributed to an overdose of collagenase in clinical trials.14 If required, the collagenase enzymes can be inactivated with a povidone-iodine wash.14

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Collagenase clostridium histolyticum.
AcenocoumarolThe risk or severity of adverse effects can be increased when Acenocoumarol is combined with Collagenase clostridium histolyticum.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Collagenase clostridium histolyticum.
AlteplaseThe risk or severity of adverse effects can be increased when Alteplase is combined with Collagenase clostridium histolyticum.
AncrodThe risk or severity of adverse effects can be increased when Ancrod is combined with Collagenase clostridium histolyticum.
AnistreplaseThe risk or severity of adverse effects can be increased when Anistreplase is combined with Collagenase clostridium histolyticum.
Antithrombin AlfaThe risk or severity of adverse effects can be increased when Antithrombin Alfa is combined with Collagenase clostridium histolyticum.
Antithrombin III humanThe risk or severity of adverse effects can be increased when Antithrombin III human is combined with Collagenase clostridium histolyticum.
ApixabanThe risk or severity of adverse effects can be increased when Apixaban is combined with Collagenase clostridium histolyticum.
ArdeparinThe risk or severity of adverse effects can be increased when Ardeparin is combined with Collagenase clostridium histolyticum.
Additional Data Available
  • Extended Description
    Extended Description
    Available for Purchase

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
    Available for Purchase

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

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International/Other Brands
Cordase
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Collagenase SantylOintment250 [arb'U]/1gTopicalSMITH & NEPHEW, INC2006-10-18Not applicableUS flag
Collagenase SantylOintment250 [arb'U]/1gTopicalHealthpoint2006-10-182017-06-30US flag
SantylOintmentTopicalSmith & Nephew, Inc.1994-12-31Not applicableCanada flag
XiaflexPowder, for solution0.9 mgIntralesionalEndo Ventures Ltd2012-11-142020-06-11Canada flag
XiaflexSolution0.9 mg/1IntralesionalEndo Pharmaceuticals Inc.2010-02-22Not applicableUS flag
XiapexInjection, powder, for solution0.9 mgIntralesionalSwedish Orphan Biovitrum Ab2011-02-28Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Kimchi Vitamin chewable multivitaminCollagenase clostridium histolyticum (5.625 mg/1) + Ascorbic acid (180 mg/1) + Cholecalciferol (0.375 mg/1) + Folic acid (0.03 mg/1) + Lactic acid (30 mg/1) + Nicotinamide (0.045 mg/1) + Pyridoxine (0.285 mg/1) + Riboflavin (0.24 mg/1) + Thiamine chloride (0.195 mg/1) + Vitamin A (0.675 mg/1) + Vitamin E (1.875 mg/1)Tablet, chewableOralTobico2010-03-18Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Kimchi Vitamin chewable multivitaminCollagenase clostridium histolyticum (5.625 mg/1) + Ascorbic acid (180 mg/1) + Cholecalciferol (0.375 mg/1) + Folic acid (0.03 mg/1) + Lactic acid (30 mg/1) + Nicotinamide (0.045 mg/1) + Pyridoxine (0.285 mg/1) + Riboflavin (0.24 mg/1) + Thiamine chloride (0.195 mg/1) + Vitamin A (0.675 mg/1) + Vitamin E (1.875 mg/1)Tablet, chewableOralTobico2010-03-18Not applicableUS flag

Categories

ATC Codes
D03BA02 — CollagenaseM09AB02 — Collagenase clostridium histolyticumD03BA52 — Collagenase, combinations
Drug Categories
Chemical TaxonomyProvided by Classyfire
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

Chemical Identifiers

UNII
9X7O8V25IT
CAS number
9001-12-1

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]
  3. Rossi AM, Katz BE: A modern approach to the treatment of cellulite. Dermatol Clin. 2014 Jan;32(1):51-9. doi: 10.1016/j.det.2013.09.005. [PubMed:24267421]
  4. Randhawa K, Shukla CJ: Non-invasive treatment in the management of Peyronie's disease. Ther Adv Urol. 2019 Feb 11;11:1756287218823671. doi: 10.1177/1756287218823671. eCollection 2019 Jan-Dec. [PubMed:30792820]
  5. Grazina R, Teixeira S, Ramos R, Sousa H, Ferreira A, Lemos R: Dupuytren's disease: where do we stand? EFORT Open Rev. 2019 Feb 20;4(2):63-69. doi: 10.1302/2058-5241.4.180021. eCollection 2019 Feb. [PubMed:30931150]
  6. Dhillon S: Collagenase Clostridium Histolyticum: A Review in Peyronie's Disease. Drugs. 2015 Aug;75(12):1405-12. doi: 10.1007/s40265-015-0441-7. [PubMed:26201462]
  7. Kaplan FT: Collagenase clostridium histolyticum injection for the treatment of Dupuytren's contracture. Drugs Today (Barc). 2011 Sep;47(9):653-67. doi: 10.1358/dot.2011.47.9.1656502. [PubMed:21971540]
  8. Krane SM: Collagenases and collagen degradation. J Invest Dermatol. 1982 Jul;79 Suppl 1:83s-86s. doi: 10.1111/1523-1747.ep12545849. [PubMed:6282982]
  9. Andrew J Watt, Vincent R Hentz: Collagenase clostridium histolyticum: a novel nonoperative treatment for Dupuytren’s disease Int. J. Clin. Rheumatol..
  10. FDA Approved Products: Qwo (collagenase clostridium histolyticum-aaes) for subcutaneous injection [Link]
  11. FDA Approved Products: Ziaflex (collagenase clostridium histolyticum) for intralesional use [Link]
  12. Thermo Fisher SDS: Collagenase, Type II Powder [Link]
  13. Endo International website [Link]
  14. FDA Approved Products: Santyl (collagenase) ointment [Link]
  15. Product monograph: Santyl (collagenase) [Link]
KEGG Compound
C00816
PubChem Substance
46506485
RxNav
58939
Therapeutic Targets Database
DAP000965
PharmGKB
PA449107
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Collagenase
AHFS Codes
  • 44:00.00 — Enzymes
  • 84:92.00 — Misc. Skin and Mucous Membrane Agents
MSDS
Download (72.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentDupuytren's Contracture of the Hand (Viking's Disease)1
4Active Not RecruitingTreatmentPeyronie's Disease1
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 / Diabetic Foot Ulcers (DFU)1
4CompletedTreatmentDupuytren's Contracture of the Hand (Viking's Disease)3
4Enrolling by InvitationTreatmentDupuytren Disease of Finger1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Abbott Laboratories Ltd.
  • Advance Biofactures Corp.
  • Auxilium Pharmaceuticals
  • BASF Corp.
  • Dispensing Solutions
  • Healthpoint Ltd.
  • Medisca Inc.
Dosage Forms
FormRouteStrength
OintmentTopical250 [arb'U]/1g
OintmentTopical120 IU
Tablet, chewableOral
OintmentTopical
OintmentTopical1.2 U
Powder, for solutionIntralesional0.9 mg
SolutionIntralesional0.9 mg/1
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
Solid
Experimental Properties
PropertyValueSource
melting point (°C)49-54https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406112/
hydrophobicity-0.714Not Available
isoelectric point5.35-6.20https://pubs.acs.org/doi/pdfplus/10.1021/bi00308a036?src=recsys

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
Curator comments
Collagenase targets many types of collagen chains. This chain has been selected as a representative collagen chain, though others may also be targeted.
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
Humans
Pharmacological action
Yes
Actions
Binder
Curator comments
Collagenase targets many types of collagen chains. This chain has been selected as a representative collagen chain, though others may also be targeted.
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
Humans
Pharmacological action
Yes
Actions
Binder
Curator comments
Collagenase targets many types of collagen chains. This chain has been selected as a representative collagen chain, though others may also be targeted.
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]

Drug created on June 13, 2005 07:24 / Updated on October 31, 2020 10:29

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