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Identification
NameAldesleukin
Accession NumberDB00041  (BIOD00082, BTD00082)
TypeBiotech
GroupsApproved
Description

Aldesleukin, a lymphokine, is produced by recombinant DNA technology using a genetically engineered E. coli strain containing an analog of the human interleukin-2 gene. Genetic engineering techniques were used to modify the human IL-2 gene, and the resulting expression clone encodes a modified human interleukin-2. This recombinant form differs from native interleukin-2 in the following ways: a) Aldesleukin is not glycosylated because it is derived from E. coli; b) the molecule has no N-terminal alanine; the codon for this amino acid was deleted during the genetic engineering procedure; c) the molecule has serine substituted for cysteine at amino acid position 125.

Protein structureDb00041
Protein chemical formulaC690H1115N177O202S6
Protein average weight15314.8000
Sequences
>Aldesleukin sequence
MAPTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCL
EEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLN
RWITFCQSIISTLT
Download FASTA Format
Synonyms
SynonymLanguageCode
IL-2Not AvailableNot Available
Interleukin-2 precursorNot AvailableNot Available
T-cell growth factorNot AvailableNot Available
TCGFNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
ProleukinChiron Corp
Brand mixturesNot Available
Categories
CAS number85898-30-2
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor treatment of adults with metastatic renal cell carcinoma.
PharmacodynamicsUsed to treat renal cell carcinoma, Aldesleukin induces the enhancement of lymphocyte mitogenesis and stimulation of long-term growth of human interleukin-2 dependent cell lines, the enhancement of lymphocyte cytotoxicity, the induction of killer cell (lymphokine-activated (LAK) and natural (NK)) activity; and the induction of interferon-gamma production. IL-2 is normally produced by the body, secreted by T cells, and stimulates growth and differentiation of T cell response. It can be used in immunotherapy to treat cancer. It enhances the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor.
Mechanism of actionAldesleukin binds to the IL-2 receptor which leads to heterodimerization of the cytoplasmic domains of the IL-2R beta and gamma(c) chains, activation of the tyrosine kinase Jak3, and phosphorylation of tyrosine residues on the IL-2R beta chain. These events led to the creation of an activated receptor complex, to which various cytoplasmic signaling molecules are recruited and become substrates for regulatory enzymes (especially tyrosine kinases) that are associated with the receptor. These events stimulate growth and differentiation of T cells.
AbsorptionNot Available
Volume of distribution

0.18 l/kg

Protein bindingNot Available
Metabolism
Route of eliminationThe pharmacokinetic profile of Proleukin is characterized by high plasma concentrations following a short IV infusion, rapid distribution into the extravascular space and elimination from the body by metabolism in the kidneys with little or no bioactive protein excreted in the urine. Following the initial rapid organ distribution, the primary route of clearance of circulating proleukin is the kidney. Greater than 80% of the amount of Proleukin distributed to plasma, cleared from the circulation and presented to the kidney is metabolized to amino acids in the cells lining the proximal convoluted tubules.
Half life13 min-85 min
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous
Prices
Unit descriptionCostUnit
Proleukin 22 million unit vial1092.34USDeach
Proleukin 22000000 unit Solution Vial976.66USDvial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.192Not Available
isoelectric point7.31Not Available
References
Synthesis Reference

Hans-Ake Fabricius, Roland Stahn, “Serum-free and mitogen-free T-cell growth factor and process for making same.” U.S. Patent US4464355, issued May, 1971.

US4464355
General ReferenceNot Available
External Links
ResourceLink
UniProtP60569
GenbankM11144
PharmGKBPA448081
Drug Product Database2130181
RxListhttp://www.rxlist.com/cgi/generic2/aldesleukin.htm
Drugs.comhttp://www.drugs.com/cdi/aldesleukin.html
WikipediaAldesleukin
ATC CodesL03AC01
AHFS Codes
  • 10:00.00
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
Clobetasol propionateCorticosteroids such as clobetasol may diminish the antineoplastic effect of aldesleukin. Avoid conccurent use of corticosteroids with aldesleukin.
ClocortoloneCorticosteroids such as clocortolone may diminish the antineoplastic effect of aldesleukin. Avoid conccurent use of corticosteroids with aldesleukin.
ClozapineAvoid combination due to enhanced adverse effects of clozapine, especially the risk of agranulocytosis.
CorticotropinCorticosteroids may diminish the antineoplastic effect of Aldesleukin. Avoid conccurent use of corticosteroids with aldesleukin.
DuloxetineMonitor therapy due to enhanced orthostatic hypotensive effect of duloxetine.
Food InteractionsNot Available

Targets

1. Interleukin-2 receptor subunit beta

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist modulator

Components

Name UniProt ID Details
Interleukin-2 receptor subunit beta P14784 Details

References:

  1. Stauber DJ, Debler EW, Horton PA, Smith KA, Wilson IA: Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2788-93. Epub 2006 Feb 13. Pubmed
  2. Steppan S, Eckart MR, Bajsarowicz K, Sternberg LR, Greve JM, Cassell DJ: Reduced secondary cytokine induction by BAY 50-4798, a high-affinity receptor-specific interleukin-2 analog. J Interferon Cytokine Res. 2006 Mar;26(3):171-8. Pubmed
  3. Cornish GH, Sinclair LV, Cantrell DA: Differential regulation of T-cell growth by IL-2 and IL-15. Blood. 2006 Jul 15;108(2):600-8. Epub 2006 Mar 28. Pubmed
  4. Lee KD, Chen HW, Chen CC, Shih YC, Liu HK, Cheng ML: Construction and characterization of a novel fusion protein consisting of anti-CD3 antibody fused to recombinant interleukin-2. Oncol Rep. 2006 May;15(5):1211-6. Pubmed
  5. Maclennan C, Hutchinson P, Holdsworth S, Bardin PG, Freezer NJ: Airway inflammation in asymptomatic children with episodic wheeze. Pediatr Pulmonol. 2006 Jun;41(6):577-83. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Interleukin-2 receptor subunit alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist modulator

Components

Name UniProt ID Details
Interleukin-2 receptor subunit alpha P01589 Details

References:

  1. Waldmann TA: Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey. J Clin Immunol. 2007 Jan;27(1):1-18. Epub 2007 Jan 11. Pubmed
  2. Recchia F, Cesta A, Rea S: Low dose interleukin-2 and 13-cis-retinoic acid as maintenance therapy in patients with solid tumors responsive to chemotherapy. J Exp Clin Cancer Res. 2003 Dec;22(4 Suppl):135-43. Pubmed
  3. Waldmann TA: Daclizumab (anti-Tac, Zenapax) in the treatment of leukemia/lymphoma. Oncogene. 2007 May 28;26(25):3699-703. Pubmed
  4. Vlad G, Ho EK, Vasilescu ER, Fan J, Liu Z, Cai JW, Jin Z, Burke E, Deng M, Cadeiras M, Cortesini R, Itescu S, Marboe C, Mancini D, Suciu-Foca N: Anti-CD25 treatment and FOXP3-positive regulatory T cells in heart transplantation. Transpl Immunol. 2007 Jul;18(1):13-21. Epub 2007 Apr 2. Pubmed
  5. Liu BY, Zhu P, Luo HB, Fu N: [Screening of short peptides binding to cell surface interleukin-2 receptor alpha chain] Nan Fang Yi Ke Da Xue Xue Bao. 2006 Jul;26(7):971-4. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Ouyang Y, Kaminski NE: Phospholipase A2 inhibitors p-bromophenacyl bromide and arachidonyl trifluoromethyl ketone suppressed interleukin-2 (IL-2) expression in murine primary splenocytes. Arch Toxicol. 1999 Feb;73(1):1-6. Pubmed

3. Cytokine receptor common subunit gamma

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Cytokine receptor common subunit gamma P31785 Details

References:

  1. Stauber DJ, Debler EW, Horton PA, Smith KA, Wilson IA: Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2788-93. Epub 2006 Feb 13. Pubmed
  2. Shibata F, Toma T, Wada T, Inoue M, Tone Y, Ohta K, Kasahara Y, Sano F, Kimura M, Ikeno M, Koizumi S, Yachie A: Skin infiltration of CD56 CD16 natural killer cells in a case of X-SCID with Omenn syndrome-like manifestations. Eur J Haematol. 2007 Jul;79(1):81-5. Pubmed
  3. Fonseca SG, Reis MM, Coelho V, Nogueira LG, Monteiro SM, Mairena EC, Bacal F, Bocchi E, Guilherme L, Zheng XX, Liew FY, Higuchi ML, Kalil J, Cunha-Neto E: Locally produced survival cytokines IL-15 and IL-7 may be associated to the predominance of CD8+ T cells at heart lesions of human chronic Chagas disease cardiomyopathy. Scand J Immunol. 2007 Aug-Sep;66(2-3):362-71. Pubmed
  4. Blank RB, Lamb EW, Tocheva AS, Crow ET, Lim KC, McKerrow JH, Davies SJ: The common gamma chain cytokines interleukin (IL)-2 and IL-7 indirectly modulate blood fluke development via effects on CD4+ T cells. J Infect Dis. 2006 Dec 1;194(11):1609-16. Epub 2006 Oct 23. Pubmed
  5. Smyth CM, Ginn SL, Deakin CT, Logan GJ, Alexander IE: Limiting {gamma}c expression differentially affects signaling via the interleukin (IL)-7 and IL-15 receptors. Blood. 2007 Jul 1;110(1):91-8. Epub 2007 Mar 15. Pubmed

Enzymes

1. Prostaglandin G/H synthase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

References:

  1. Pyeon D, Diaz FJ, Splitter GA: Prostaglandin E(2) increases bovine leukemia virus tax and pol mRNA levels via cyclooxygenase 2: regulation by interleukin-2, interleukin-10, and bovine leukemia virus. J Virol. 2000 Jun;74(12):5740-5. Pubmed
  2. Hamada T, Tsuchihashi S, Avanesyan A, Duarte S, Moore C, Busuttil RW, Coito AJ: Cyclooxygenase-2 deficiency enhances Th2 immune responses and impairs neutrophil recruitment in hepatic ischemia/reperfusion injury. J Immunol. 2008 Feb 1;180(3):1843-53. Pubmed

2. Cytosolic phospholipase A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytosolic phospholipase A2 P47712 Details

References:

  1. Wolbink GJ, Schalkwijk C, Baars JW, Wagstaff J, van den Bosch H, Hack CE: Therapy with interleukin-2 induces the systemic release of phospholipase-A2. Cancer Immunol Immunother. 1995 Nov;41(5):287-92. Pubmed

3. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Elkahwaji J, Robin MA, Berson A, Tinel M, Letteron P, Labbe G, Beaune P, Elias D, Rougier P, Escudier B, Duvillard P, Pessayre D: Decrease in hepatic cytochrome P450 after interleukin-2 immunotherapy. Biochem Pharmacol. 1999 Apr 15;57(8):951-4. Pubmed
  2. Sunman JA, Hawke RL, LeCluyse EL, Kashuba AD: Kupffer cell-mediated IL-2 suppression of CYP3A activity in human hepatocytes. Drug Metab Dispos. 2004 Mar;32(3):359-63. Pubmed

4. Xanthine dehydrogenase/oxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Xanthine dehydrogenase/oxidase P47989 Details

References:

  1. Faggioni R, Allavena P, Cantoni L, Carelli M, Demitri MT, Delgado R, Gatti S, Gnocchi P, Isetta AM, Paganin C, et al.: Mechanisms of interleukin-2-induced hydrothoraxy in mice: protective effect of endotoxin tolerance and dexamethasone and possible role of reactive oxygen intermediates. J Immunother Emphasis Tumor Immunol. 1994 Apr;15(3):194-201. Pubmed

5. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Elkahwaji J, Robin MA, Berson A, Tinel M, Letteron P, Labbe G, Beaune P, Elias D, Rougier P, Escudier B, Duvillard P, Pessayre D: Decrease in hepatic cytochrome P450 after interleukin-2 immunotherapy. Biochem Pharmacol. 1999 Apr 15;57(8):951-4. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 13, 2013 10:48