DrugBank: Alpha-1-proteinase inhibitor (DB00058)

targets (1)

Identification

Name

Alpha-1-proteinase inhibitor

Accession Number

DB00058 (BIOD00002, BTD00002)

Type

biotech

Groups

approved

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

Display: 3D Structure

Protein chemical formula

C₂₀₀₁H₃₁₃₀N₅₁₄O₆₀₁S₁₀

Protein average weight

44324.5000

Sequences

>DB00058 sequence
EDPQGDAAQKTDTSHHDQDHPTFNKITPNLAEFAFSLYRQLAHQSNSTNIFFSPVSIATA
FAMLSLGTKADTHDEILEGLNFNLTEIPEAQIHEGFQELLRTLNQPDSQLQLTTGNGLFL
SEGLKLVDKFLEDVKKLYHSEAFTVNFGDTEEAKKQINDYVEKGTQGKIVDLVKELDRDT
VFALVNYIFFKGKWERPFEVKDTEEEDFHVDQVTTVKVPMMKRLGMFNIQHCKKLSSWVL
LMKYLGNATAIFFLPDEGKLQHLENELTHDIITKFLENEDRRSASLHLPKLSITGTYDLK
SVLGQLGITKVFSNGADLSGVTEEAPLKLSKAVHKAVLTIDEKGTEAAGAMFLEAIPMSI
PPEVKFNKPFVFLMIEQNTKSPLFMGKVVNPTQK

FASTA

Synonyms

Alpha 1-antitrypsin
Alpha-1 protease inhibitor
Alpha-1-antiproteinase
Alpha-1-antitrypsin precursor

Salts

Not Available

Brand names

Name	Company
Aralast (Baxter)
Prolastin (Talecris Biotherapeutics C formerly Bayer)

Brand mixtures

Not Available

Categories

Enzyme Replacement Agents

CAS number

9041-92-3

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

For treatment of panacinar emphysema

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.

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

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Dosage forms

Form	Route	Strength
Injection, powder, lyophilized, for solution	Intravenous

Prices

Unit description	Cost	Unit
Aralast 1000 mg vial	0.52 USD	vial
Aralast np 1000 mg vial	0.52 USD	vial
Aralast np 500 mg vial	0.52 USD	vial
Aralast 500 mg vial	0.5 USD	vial
Zemaira 1000 mg vial	0.5 USD	vial
Prolastin 1000 mg vial	0.46 USD	vial
Prolastin 500 mg vial	0.46 USD	vial
Prolastin c 1000 mg vial	0.46 USD	vial

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

liquid

Experimental Properties

Property	Value	Source
melting point	59 °C at pH 7.8	Tew D.J., Bottomley, S.P. J. Mol. Biol. 313:1161-1169 (2001)
hydrophobicity	-0.302	Not Available
isoelectric point	5.37	Not Available

References

Synthesis Reference

Not Available

General Reference

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

External Links

Resource	Link
UniProt	P01009
Genbank	K01396
PharmGKB	PA10308
Drug Product Database	2204606
RxList	http://www.rxlist.com/cgi/generic3/zemaira.htm
Wikipedia	http://en.wikipedia.org/wiki/Alpha_1-antitrypsin

ATC Codes

Not Available

AHFS Codes

Not Available

PDB Entries

1QLP

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Leukocyte elastase Pharmacological action: yes Actions: inhibitor Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis Organism class: human UniProt ID: P08246 Gene: ELA2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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. 2010 Jun 3. Pubmed 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 Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Targets

1. Leukocyte elastase

Pharmacological action: yes
Actions: inhibitor

Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis

Organism class: human
UniProt ID: P08246 Link_out

Gene: ELA2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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. 2010 Jun 3. Pubmed
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
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on September 29, 2010 14:34