Alpha-1-proteinase inhibitor

Identification

Name
Alpha-1-proteinase inhibitor
Accession Number
DB00058
Description

Human alpha-1 proteinase inhibitor or alpha-1-antitrypsin, prepared from human plasma via Cohn alcohol fractionation followed by PEG and zinc chloride fractionation.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Other protein based therapies
Protein Structure
Db00058
Protein Chemical Formula
C2001H3130N514O601S10
Protein Average Weight
44324.5 Da
Sequences
>DB00058 sequence
EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAEFAFSLYRQLAHQSNSTNIFFSPVSIATA
FAMLSLGTKADTHDEILEGLNFNLTEIPEAQIHEGFQELLRTLNQPDSQLQLTTGNGLFL
SEGLKLVDKFLEDVKKLYHSEAFTVNFGDTEEAKKQINDYVEKGTQGKIVDLVKELDRDT
VFALVNYIFFKGKWERPFEVKDTEEEDFHVDQVTTVKVPMMKRLGMFNIQHCKKLSSWVL
LMKYLGNATAIFFLPDEGKLQHLENELTHDIITKFLENEDRRSASLHLPKLSITGTYDLK
SVLGQLGITKVFSNGADLSGVTEEAPLKLSKAVHKAVLTIDEKGTEAAGAMFLEAIPMSI
PPEVKFNKPFVFLMIEQNTKSPLFMGKVVNPTQK
Download FASTA Format
Synonyms
  • Alfa 1-proteinase inhibitor (human)
  • Alfa-1-antitripsina
  • Alfa1 antitrypsin
  • Alpha 1-antitrypsin
  • Alpha 1-Proteinase Inhibitor
  • Alpha 1-proteinase inhibitor (human)
  • Alpha 1-proteinase inhibitor, human
  • Alpha-1 protease inhibitor
  • Alpha-1 proteinase inhibitor (human)
  • Alpha-1-antiproteinase
  • Alpha-1-antitrypsin
  • Alpha-1-proteinase Inhibitor (human)
  • Alpha-1-proteinase inhibitor human
  • Alpha-1-proteinase Inhibitor, Human
  • Alpha-1-proteinase inhibitor,human
  • Alpha1-proteinase Inhibitor
  • Alpha1-proteinase inhibitor (human)
  • alpha1-proteinase inhibitor human
  • API
External IDs
  • 232-924-7

Pharmacology

Indication

For chronic augmentation and maintenance therapy in individuals with alpha1-proteinase inhibitor (A1-PI) deficiency and clinical evidence of emphysema.

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

Prevents excessive accumulation of active neutrophil elastase and consequent proteolysis of elastin tissues in alveolar lung structures. This prevents the development of emphysema.

Mechanism of action

Alpha-1 proteinase inhibitor is a serine protease inhibitor (Serpin). Its primary mechanism is inhibiting the action of the serine protease called elastase (also plasmin and thrombin) in the lungs. The reactive center loop (RCL) of alpha-1 proteinase inhibitor extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.

TargetActionsOrganism
ANeutrophil elastase
inhibitor
Humans
Absorption
Not Available
Volume of distribution
  • 5632 ± 2006 mL [ARALAST NP]
  • 5618 ± 1618 mL [Aralast]
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life
Not Available
Clearance
  • 940 +/- 275 mL/day [Patients with congenital α1-PI deficiency with single IV infusion of 60 mg/kg]
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
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
Albutrepenonacog alfaAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Albutrepenonacog alfa.
Aminocaproic acidAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Aminocaproic acid.
Andexanet alfaAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Andexanet alfa.
Anti-inhibitor coagulant complexAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Anti-inhibitor coagulant complex.
Antihemophilic Factor (Recombinant), PEGylatedAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Antihemophilic Factor (Recombinant), PEGylated.
Antihemophilic factor humanAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Antihemophilic factor human.
Antihemophilic factor, human recombinantAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Antihemophilic factor, human recombinant.
AprotininAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Aprotinin.
Beroctocog alfaAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Beroctocog alfa.
Calcium acetateAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Calcium acetate.
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
Not Available

Products

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International/Other Brands
Aralast (Baxter) / Prolastin (Talecris Biotherapeutics C formerly Bayer)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Alpha1-proteinase Inhibitor (human)Powder, for solutionIntravenousGrifols Therapeutics LlcNot applicableNot applicableCanada flag
Alpha1-proteinase Inhibitor (human)Powder, for solutionIntravenousGrifols Therapeutics LlcNot applicableNot applicableCanada flag
Aralast NPKit16 mg/1mLIntravenousBaxalta u.s. Inc.2002-12-23Not applicableUS flag
Aralast NPKit16 mg/1mLIntravenousBaxter Laboratories2010-09-012014-11-09US flag
Aralast NPKit16 mg/1mLIntravenousBaxter Laboratories2010-09-012014-11-09US flag
Aralast NPKit16 mg/1mLIntravenousBaxalta u.s. Inc.2002-12-23Not applicableUS flag
Aralast NPKit16 mg/1mLIntravenousBaxter Laboratories2010-04-192014-11-09US flag
GlassiaInjection, solution1 g/50mLIntravenousBaxalta Usa Inc.2010-07-01Not applicableUS flag
Prolastin Inj 25.0mg/mlPowder, for solutionIntravenousCutter Biological, Division Of Miles Lab Inc.1988-12-311998-09-25Canada flag
Prolastin-C1000 mg/20mLIntravenousGRIFOLS USA, LLC1987-12-02Not applicableUS 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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Categories

ATC Codes
B02AB02 — Alfa1 antitrypsin
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
F43I396OIS
CAS number
9041-92-3

References

Synthesis Reference

Michael H. Coan, William J. Brockway, "Method of preparing alpha-1-proteinase inhibitor." U.S. Patent US4379087, issued December, 1968.

US4379087
General References
  1. Karnaukhova E, Ophir Y, Golding B: Recombinant human alpha-1 proteinase inhibitor: towards therapeutic use. Amino Acids. 2006 Jun;30(4):317-32. Epub 2006 May 26. [PubMed:16773239]
UniProt
P01009
Genbank
K01396
PubChem Substance
46506364
RxNav
535
Therapeutic Targets Database
DAP001102
PharmGKB
PA10308
RxList
RxList Drug Page
Wikipedia
Alpha-1_antitrypsin
AHFS Codes
  • 44:00.00 — Enzymes
FDA label
Download (101 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentPancreatitis, Chronic; Diabetes; Transplant1
4CompletedTreatmentAlpha 1-Antitrypsin Deficiency1
4CompletedTreatmentAlpha 1-proteinase Inhibitor Deficiency / Emphysema1
4CompletedTreatmentAlpha-1 Anti-trypsin Deficiency / Healthy Volunteers1
4CompletedTreatmentAlpha1-proteinase Inhibitor Deficiency / Emphysema1
4TerminatedTreatmentAlpha-1 Anti-trypsin Deficiency1
4WithdrawnTreatmentAlpha-1 Anti-trypsin Deficiency / Chronic Obstructive Pulmonary Disease (COPD)1
3CompletedTreatmentAlpha 1-Antitrypsin Deficiency2
3CompletedTreatmentAlpha-1 Anti-trypsin Deficiency1
3Enrolling by InvitationTreatmentPulmonary Emphysema in Alpha-1 Antitrypsin Deficiency1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Baxter International Inc.
  • CSL Behring LLC
  • Talecris Biotherapeutics
Dosage Forms
FormRouteStrength
KitIntravenous16 mg/1mL
Injection, solutionIntravenous1 g/50mL
Injection, powder, for solutionParenteral1000 mg
InjectionIntravenous1000 mg
Powder, for solutionIntravenous
Powder, for solutionIntravenous1000 mg
Injection, solutionIntravenous1000 mg/20mL
SolutionIntravenous1000 mg
Injection, powder, lyophilized, for solutionIntravenous1000 mg
Injection, powder, for solutionIntravenous1000 mg
KitIntravenous1000 mg/20mL
KitIntravenous4000 mg/76mL
KitIntravenous5000 mg/95mL
Kit; powder, for solutionIntravenous1000 mg
Kit; powder, for solutionIntravenous4000 mg
Kit; powder, for solutionIntravenous5000 mg
Prices
Unit descriptionCostUnit
Aralast 1000 mg vial0.52USD vial
Aralast np 1000 mg vial0.52USD vial
Aralast np 500 mg vial0.52USD vial
Aralast 500 mg vial0.5USD vial
Zemaira 1000 mg vial0.5USD vial
Prolastin 1000 mg vial0.46USD vial
Prolastin 500 mg vial0.46USD vial
Prolastin c 1000 mg vial0.46USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)59 °C at pH 7.8Tew D.J., Bottomley, S.P. J. Mol. Biol. 313:1161-1169 (2001)
hydrophobicity-0.302Not Available
isoelectric point5.37Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type endopeptidase activity
Specific Function
Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.
Gene Name
ELANE
Uniprot ID
P08246
Uniprot Name
Neutrophil elastase
Molecular Weight
28517.81 Da
References
  1. Topic A, Ljujic M, Nikolic A, Petrovic-Stanojevic N, Dopudja-Pantic V, Mitic-Milikic M, Radojkovic D: Alpha-1-antitrypsin phenotypes and neutrophil elastase gene promoter polymorphisms in lung cancer. Pathol Oncol Res. 2011 Mar;17(1):75-80. doi: 10.1007/s12253-010-9283-5. Epub 2010 Jun 3. [PubMed:20521180]
  2. Karnaukhova E, Ophir Y, Golding B: Recombinant human alpha-1 proteinase inhibitor: towards therapeutic use. Amino Acids. 2006 Jun;30(4):317-32. Epub 2006 May 26. [PubMed:16773239]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on November 30, 2020 13:38

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