Collagenase clostridium histolyticum
Identification
- Summary
Collagenase clostridium histolyticum is a collagenase enzyme used to promote debridement of necrotic tissue in burns and skin ulcers as well as to treat Dupuytren's contracture and Peyronie's disease.
- Brand Names
- Qwo, Santyl, Xiaflex
- Generic Name
- Collagenase clostridium histolyticum
- DrugBank Accession Number
- DB00048
- Background
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
- 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
- Clostridiopeptidase A
- 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
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Dupuytren’s contracture •••••••••••• ••••• •••••••• •••• ••••••••• Management of Peyronie’s disease •••••••••••• ••••• •• ••••• •• •••••• ••••• •••••• •••••••••• •••••••• ••••••••••• ••••••• ••••••••• Treatment of Necrotic tissue •••••••••••• •••••••• Treatment of Necrotic tissue •••••••••••• •••••••• - Contraindications & Blackbox Warnings
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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
Target Actions Organism ACollagen alpha-1(I) chain binderHumans ACollagen alpha-1(II) chain binderHumans ACollagen alpha-1(III) chain binderHumans - 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Collagenase clostridium histolyticum. Acenocoumarol The risk or severity of adverse effects can be increased when Acenocoumarol is combined with Collagenase clostridium histolyticum. Alteplase The risk or severity of adverse effects can be increased when Alteplase is combined with Collagenase clostridium histolyticum. Ancrod The risk or severity of adverse effects can be increased when Ancrod is combined with Collagenase clostridium histolyticum. Anistreplase The risk or severity of adverse effects can be increased when Anistreplase is combined with Collagenase clostridium histolyticum. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Cordase
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Collagenase Santyl Ointment 250 [arb'U]/1g Topical SMITH & NEPHEW, INC 2006-10-18 Not applicable US Collagenase Santyl Ointment 250 [arb'U]/1g Topical Healthpoint 2006-10-18 2017-06-30 US Qwo Injection, powder, lyophilized, for solution 0.23 mg/1mL Intralesional Endo Aesthetics LLC 2021-02-01 2025-01-31 US Santyl Ointment 250 unit / g Topical Smith & Nephew, Inc. 1994-12-31 Not applicable Canada Xiaflex Powder, for solution 0.9 mg / vial Intralesional Endo Ventures Ltd 2012-11-14 2020-06-11 Canada - Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image IRUXOL MONO Ointment 1.2 IU Topical SMITH & NEPHEW HEALTHCARE SDN BHD 2020-09-08 Not applicable Malaysia - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Kimchi Vitamin chewable multivitamin Collagenase 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, chewable Oral Tobico 2010-03-18 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Kimchi Vitamin chewable multivitamin Collagenase 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, chewable Oral Tobico 2010-03-18 Not applicable US
Categories
- ATC Codes
- D03BA02 — Collagenase
- D03BA — Proteolytic enzymes
- D03B — ENZYMES
- D03 — PREPARATIONS FOR TREATMENT OF WOUNDS AND ULCERS
- D — DERMATOLOGICALS
- M09AB — Enzymes
- M09A — OTHER DRUGS FOR DISORDERS OF THE MUSCULO-SKELETAL SYSTEM
- M09 — OTHER DRUGS FOR DISORDERS OF THE MUSCULO-SKELETAL SYSTEM
- M — MUSCULO-SKELETAL SYSTEM
- Drug Categories
- Collagen-specific Enzyme
- Collagenases
- Dermatologicals
- Endopeptidases
- Enzymes
- Enzymes and Coenzymes
- Hydrolases
- Metalloendopeptidases
- Metalloproteases
- Microbial Collagenase, antagonists & inhibitors
- Misc. Skin and Mucous Membrane Agents
- Musculo-Skeletal System
- Peptide Hydrolases
- Preparations for Treatment of Wounds and Ulcers
- 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
- Affected organisms
- Humans and other mammals
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
- Norris DB, Trudgill PW: Multiple forms of cyclohexanone oxygenase from Nocardia globerula CL1. Eur J Biochem. 1976 Mar 16;63(1):193-8. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Krane SM: Collagenases and collagen degradation. J Invest Dermatol. 1982 Jul;79 Suppl 1:83s-86s. doi: 10.1111/1523-1747.ep12545849. [Article]
- Andrew J Watt, Vincent R Hentz: Collagenase clostridium histolyticum: a novel nonoperative treatment for Dupuytren’s disease Int. J. Clin. Rheumatol.. [Article]
- FDA Approved Products: Qwo (collagenase clostridium histolyticum-aaes) for subcutaneous injection [Link]
- FDA Approved Products: Ziaflex (collagenase clostridium histolyticum) for intralesional use [Link]
- Thermo Fisher SDS: Collagenase, Type II Powder [Link]
- Endo International website [Link]
- FDA Approved Products: Santyl (collagenase) ointment [Link]
- Product monograph: Santyl (collagenase) [Link]
- External Links
- KEGG Compound
- C00816
- PubChem Substance
- 46506485
- 58939
- Therapeutic Targets Database
- DAP000965
- PharmGKB
- PA449107
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Collagenase
- MSDS
- Download (72.9 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Dupuytren's Contracture of the Hand (Viking's Disease) 1 4 Active Not Recruiting Treatment Dupuytren's Disease of Finger 1 4 Active Not Recruiting Treatment Peyronie's Disease 1 4 Completed Basic Science Impaired Wound Healing / Scarring 1 4 Completed Diagnostic Diabetic Foot Ulcers (DFUs) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Abbott Laboratories Ltd.
- Advance Biofactures Corp.
- Auxilium Pharmaceuticals
- BASF Corp.
- Dispensing Solutions
- Healthpoint Ltd.
- Medisca Inc.
- Dosage Forms
Form Route Strength Ointment Topical 250 [arb'U]/1g Ointment Topical Ointment Topical 120 IU Ointment Topical 1.2 IU Ointment Topical 1.2 u/g Tablet, chewable Oral Injection, powder, lyophilized, for solution Intralesional 0.23 mg/1mL Ointment Topical 250 unit / g Ointment Topical 1.2 U Injection, powder, lyophilized, for solution; kit Intralesional 0.9 mg/1 Powder, for solution Intralesional 0.9 mg / vial Injection, powder, for solution Intralesional 0.9 mg Powder Intralesional 0.9 MG Ointment Topical 1.2 units/g - Prices
Unit description Cost Unit Xiaflex 0.9 mg vial 3900.0USD vial Collagenase powder 2432.7USD g Santyl 250 unit/gm Ointment 15 gm Tube 62.98USD tube Santyl ointment 4.13USD g DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 49-54 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406112/ hydrophobicity -0.714 Not Available isoelectric point 5.35-6.20 https://pubs.acs.org/doi/pdfplus/10.1021/bi00308a036?src=recsys
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 21, 2024 02:33