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 solution1 gIntravenousGrifols Therapeutics Inc.Not applicableNot applicableCanada
Alpha1-proteinase Inhibitor (human)Powder, for solution500 mgIntravenousGrifols Therapeutics Inc.Not applicableNot applicableCanada
Aralast NPKitBaxalta u.s. Inc.2002-12-23Not applicableUs
Aralast NPKitBaxalta u.s. Inc.2002-12-23Not applicableUs
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-CPowder, for solution1000 mgIntravenousGrifols Therapeutics Inc.1996-11-11Not applicableCanada
Prolastin-CKitGrifols1987-12-02Not applicableUs
Prolastin-CKitGrifols1987-12-02Not applicableUs
Prolastin-CKitGrifols1987-12-02Not 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.

Structured Indications
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
DrugInteractionDrug group
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved, Investigational
AlfuzosinThe serum concentration of Alfuzosin can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved, Investigational
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved, Illicit, Investigational
Ambroxol acefyllinateThe serum concentration of Ambroxol acefyllinate can be decreased when it is combined with Alpha-1-proteinase inhibitor.Experimental, Investigational
AmineptineThe serum concentration of Amineptine can be increased when it is combined with Alpha-1-proteinase inhibitor.Illicit, Withdrawn
AminophyllineThe serum concentration of Aminophylline can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
AmitriptylineThe serum concentration of Amitriptyline can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
AmoxapineThe serum concentration of Amoxapine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
BoceprevirThe serum concentration of Alpha-1-proteinase inhibitor can be decreased when it is combined with Boceprevir.Approved, Withdrawn
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved, Investigational
CabergolineThe serum concentration of Cabergoline can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
CarbamazepineThe metabolism of Alpha-1-proteinase inhibitor can be increased when combined with Carbamazepine.Approved, Investigational
ChlorotrianiseneThe serum concentration of Chlorotrianisene can be decreased when it is combined with Alpha-1-proteinase inhibitor.Investigational, Withdrawn
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved, Investigational, Withdrawn
ClarithromycinThe therapeutic efficacy of Clarithromycin can be decreased when used in combination with Alpha-1-proteinase inhibitor.Approved
ClomipramineThe serum concentration of Clomipramine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved, Vet Approved
Conjugated estrogensThe serum concentration of Conjugated estrogens can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
CyclobenzaprineThe serum concentration of Cyclobenzaprine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
CyclophosphamideThe risk or severity of adverse effects can be increased when Alpha-1-proteinase inhibitor is combined with Cyclophosphamide.Approved, Investigational
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved, Investigational, Vet Approved
DelavirdineThe serum concentration of Delavirdine can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
DesipramineThe serum concentration of Desipramine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
DibenzepinThe serum concentration of Dibenzepin can be increased when it is combined with Alpha-1-proteinase inhibitor.Experimental
DienestrolThe serum concentration of Dienestrol can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved, Investigational
DiethylstilbestrolThe serum concentration of Diethylstilbestrol can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved, Investigational
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
DihydroergotamineThe serum concentration of Dihydroergotamine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Alpha-1-proteinase inhibitor.Approved
DosulepinThe serum concentration of Dosulepin can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
DoxepinThe serum concentration of Doxepin can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
DyphyllineThe serum concentration of Dyphylline can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
EnfuvirtideThe serum concentration of Enfuvirtide can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved, Investigational
Ergoloid mesylateThe serum concentration of Ergoloid mesylate can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
ErgonovineThe serum concentration of Ergonovine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
ErgotamineThe serum concentration of Ergotamine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
EsmirtazapineThe serum concentration of Esmirtazapine can be increased when it is combined with Alpha-1-proteinase inhibitor.Investigational
EstradiolThe serum concentration of Estradiol can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved, Investigational, Vet Approved
EstramustineThe serum concentration of Estramustine can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
Estrogens, esterifiedThe serum concentration of Estrogens, esterified can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
Estrone sulfateThe serum concentration of Estrone sulfate can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
Ethinyl EstradiolThe serum concentration of Ethinyl Estradiol can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
EtravirineThe serum concentration of Etravirine can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
Fibrinogen HumanThe risk or severity of adverse effects can be increased when Alpha-1-proteinase inhibitor is combined with Fibrinogen Human.Approved
GarlicThe serum concentration of Alpha-1-proteinase inhibitor can be decreased when it is combined with Garlic.Approved
HexestrolThe serum concentration of Hexestrol can be decreased when it is combined with Alpha-1-proteinase inhibitor.Withdrawn
ImipramineThe serum concentration of Imipramine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
IprindoleThe serum concentration of Iprindole can be increased when it is combined with Alpha-1-proteinase inhibitor.Experimental
LofepramineThe serum concentration of Lofepramine can be increased when it is combined with Alpha-1-proteinase inhibitor.Experimental
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved, Investigational
MestranolThe serum concentration of Mestranol can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
MethallenestrilThe serum concentration of Methallenestril can be decreased when it is combined with Alpha-1-proteinase inhibitor.Experimental
MethylergometrineThe serum concentration of Methylergometrine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved, Illicit
MirtazapineThe serum concentration of Mirtazapine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
NefazodoneThe serum concentration of Nefazodone can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved, Withdrawn
NortriptylineThe serum concentration of Nortriptyline can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
OpipramolThe serum concentration of Opipramol can be increased when it is combined with Alpha-1-proteinase inhibitor.Investigational
PethidineThe risk or severity of adverse effects can be increased when Alpha-1-proteinase inhibitor is combined with Pethidine.Approved
PimozideThe serum concentration of Pimozide can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
ProtriptylineThe serum concentration of Protriptyline can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
RiociguatThe serum concentration of Riociguat can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
SildenafilThe serum concentration of Sildenafil can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved, Investigational
SimeprevirThe serum concentration of Simeprevir can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
St. John's WortThe metabolism of Alpha-1-proteinase inhibitor can be increased when combined with St. John's Wort.Investigational, Nutraceutical
Synthetic Conjugated Estrogens, AThe serum concentration of Synthetic Conjugated Estrogens, A can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Alpha-1-proteinase inhibitor.Approved, Investigational
TemsirolimusThe risk or severity of adverse effects can be increased when Alpha-1-proteinase inhibitor is combined with Temsirolimus.Approved
TheophyllineThe serum concentration of Theophylline can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
TianeptineThe serum concentration of Tianeptine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved, Investigational
TipranavirThe serum concentration of Alpha-1-proteinase inhibitor can be decreased when it is combined with Tipranavir.Approved, Investigational
TretinoinTretinoin may increase the thrombogenic activities of Alpha-1-proteinase inhibitor.Approved, Investigational, Nutraceutical
TriazolamThe serum concentration of Triazolam can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
TrimipramineThe serum concentration of Trimipramine can be increased when it is combined with Alpha-1-proteinase inhibitor.Approved
Valproic AcidThe serum concentration of Valproic Acid can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved, Investigational
VerapamilThe metabolism of Verapamil can be decreased when combined with Alpha-1-proteinase inhibitor.Approved
ZidovudineThe serum concentration of Zidovudine can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
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 RecruitingTreatmentNew Onset Type-1 Diabetes1
2CompletedTreatmentAlpha 1 Antitrypsin Deficiency1
2CompletedTreatmentAlpha 1-Antitrypsin Deficiency1
2CompletedTreatmentAlpha 1-antitrypsin Deficiency (AATD) / Emphysema1
2CompletedTreatmentCystic Fibrosis (CF)2
2RecruitingTreatmentDiabetes, Diabetes Mellitus Type 1 / Transplant, Kidney1
2RecruitingTreatmentLung Transplantation Rejection / Transplantation, Lung Rejection1
2TerminatedTreatmentCystic Fibrosis (CF)1
2TerminatedTreatmentDiabetes, Diabetes Mellitus Type 11
2WithdrawnTreatmentDiabetes, Diabetes Mellitus Type 11
2, 3CompletedTreatmentAlpha-1 Anti-trypsin Deficiency1
2, 3CompletedTreatmentEmphysema1
2, 3SuspendedTreatmentGraft Versus Host Disease (GVHD)1
2, 3TerminatedBasic ScienceHuman Immunodeficiency Virus (HIV)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
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous1 g
Powder, for solutionIntravenous500 mg
Injection, solutionIntravenous1 g/50mL
Powder, for solutionIntravenous25 mg
Powder, for solutionIntravenous1000 mg
Injection, powder, for solutionIntravenous1000 mg
Kit
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 December 10, 2017 17:18