Alpha-1-proteinase inhibitor

Identification

Name
Alpha-1-proteinase inhibitor
Accession Number
DB00058  (BTD00002, BIOD00002)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Other protein based therapies
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.

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
  • 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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Alpha1-proteinase Inhibitor (human)Powder, for solution500 mgIntravenousGrifols Therapeutics Inc.Not applicableNot applicableCanada
Alpha1-proteinase Inhibitor (human)Powder, for solution1 gIntravenousGrifols Therapeutics Inc.Not applicableNot applicableCanada
Aralast NPKit16 mg/1mLBaxter Laboratories2010-04-192014-11-09Us
Aralast NPKit16 mg/1mLBaxalta u.s. Inc.2002-12-23Not applicableUs
Aralast NPKit16 mg/1mLBaxter Laboratories2010-09-012014-11-09Us
Aralast NPKit16 mg/1mLBaxalta u.s. Inc.2002-12-23Not applicableUs
Aralast NPKit16 mg/1mLBaxter Laboratories2010-09-012014-11-09Us
GlassiaInjection, solution1 g/50mLIntravenousBaxalta Usa Inc.2010-07-01Not applicableUs
Prolastin Inj 25.0mg/mlPowder, for solution25 mgIntravenousCutter Biological, Division Of Miles Lab Inc.1988-12-311998-09-25Canada
Prolastin-CKit1000 mg/20mLGrifols1987-12-02Not applicableUs
International/Other Brands
Aralast (Baxter) / Glassia / Prolastin (Talecris Biotherapeutics C formerly Bayer) / Prolastin-C
Categories
UNII
F43I396OIS
CAS number
9041-92-3

Pharmacology

Indication

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

Associated Conditions
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
Human
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]
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Aminocaproic AcidAminocaproic Acid may increase the thrombogenic activities of Alpha-1-proteinase inhibitor.
Aminomethylbenzoic acidAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Aminomethylbenzoic 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 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.
AprotininAprotinin may increase the thrombogenic activities of Alpha-1-proteinase inhibitor.
Beroctocog alfaAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Beroctocog alfa.
CamostatAlpha-1-proteinase inhibitor may increase the thrombogenic activities of Camostat.
Coagulation Factor IX (Recombinant)Alpha-1-proteinase inhibitor may increase the thrombogenic activities of Coagulation Factor IX (Recombinant).
Food Interactions
Not Available

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]
External Links
UniProt
P01009
Genbank
K01396
PubChem Substance
46506364
Therapeutic Targets Database
DAP001102
PharmGKB
PA10308
RxList
RxList Drug Page
Wikipedia
Alpha_1-antitrypsin
ATC Codes
B02AB02 — Alfa1 antitrypsin
AHFS Codes
  • 44:00.00 — Enzymes
FDA label
Download (101 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAlpha 1-Antitrypsin Deficiency1
1CompletedTreatmentDiabetes Mellitus (DM) / Diabetes, Diabetes Mellitus Type 11
1TerminatedTreatmentDiabetes, Diabetes Mellitus Type 11
1TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1Unknown StatusTreatmentNeuromyelitis Optica1
1, 2CompletedSupportive CareGraft Versus Host Disease (GVHD)1
1, 2CompletedTreatmentAcute Myocardial Infarction (AMI)1
1, 2CompletedTreatmentAlpha-1 Anti-trypsin Deficiency1
1, 2CompletedTreatmentDiabetes, Diabetes Mellitus Type 11
1, 2Enrolling by InvitationTreatmentAlpha-1 Anti-trypsin Deficiency1
1, 2RecruitingPreventionPancreatitis, Chronic1
1, 2Unknown StatusTreatmentPost Cardiac Surgery Systemic Inflammatory Response1
2Active Not RecruitingTreatmentGraft Versus Host Disease (GVHD)1
2Active Not RecruitingTreatmentLung Transplantation Rejection / Transplantation, Lung Rejection1
2CompletedTreatmentAlpha 1 Antitrypsin Deficiency1
2CompletedTreatmentAlpha 1-Antitrypsin Deficiency1
2CompletedTreatmentAlpha 1-antitrypsin Deficiency (AATD) / Emphysema1
2CompletedTreatmentCystic Fibrosis (CF)2
2CompletedTreatmentNew Onset Type-1 Diabetes1
2RecruitingPreventionGraft Versus Host Disease (GVHD)1
2RecruitingTreatmentDiabetes, Diabetes Mellitus Type 1 / Transplant, Kidney1
2TerminatedTreatmentCystic Fibrosis (CF)1
2TerminatedTreatmentDiabetes, Diabetes Mellitus Type 11
2WithdrawnTreatmentAlpha 1-Antitrypsin Deficiency1
2WithdrawnTreatmentDiabetes, Diabetes Mellitus Type 11
2, 3CompletedTreatmentAlpha-1 Anti-trypsin Deficiency1
2, 3CompletedTreatmentEmphysema1
2, 3TerminatedBasic ScienceHuman Immunodeficiency Virus (HIV)1
2, 3TerminatedTreatmentGraft Versus Host Disease (GVHD)1
3CompletedTreatmentAlpha 1-Antitrypsin Deficiency2
3Enrolling by InvitationTreatmentPulmonary Emphysema in Alpha-1 Antitrypsin Deficiency1
3RecruitingPreventionAlpha-1 Anti-trypsin Deficiency1
3RecruitingTreatmentPulmonary Emphysema in Alpha-1 PI Deficiency1
4CompletedTreatmentAlpha 1-Antitrypsin Deficiency1
4CompletedTreatmentAlpha 1-proteinase Inhibitor Deficiency / Emphysema1
4CompletedTreatmentAlpha-1 Anti-trypsin Deficiency / Healthy Volunteers1
4CompletedTreatmentAlpha1-proteinase Inhibitor Deficiency / Emphysema1
4RecruitingTreatmentAlpha-1 Anti-trypsin Deficiency / Chronic Obstructive Pulmonary Disease (COPD)1
4RecruitingTreatmentPancreatitis, Chronic; Diabetes; Transplant1
Not AvailableAvailableNot AvailableAcute Graft-Versus-Host Reaction Following Bone Marrow Transplant / Acute-graft-versus-host Disease / Alpha 1-Antitrypsin Deficiency / Alpha-1 Protease Inhibitor Deficiency / Alpha-1 Proteinase Inhibitor / Graft Versus Host Disease (GVHD) / SR aGvHD / Steroid Refractory Acute Graft Versus Host Disease1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Baxter International Inc.
  • CSL Behring LLC
  • Talecris Biotherapeutics
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous1 g
Powder, for solutionIntravenous500 mg
Kit16 mg/1mL
Injection, solutionIntravenous1 g/50mL
Powder, for solutionIntravenous25 mg
Kit1000 mg/20mL
Powder, for solutionIntravenous1000 mg
Injection, solutionIntravenous1000 mg/20mL
Injection, powder, for solutionIntravenous1000 mg
Kit; powder, for solutionIntravenous1000 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

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
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 September 21, 2018 20:42