Muromonab

Identification

Summary

Muromonab is a monoclonal anti-CD3 antibody used as immunosuppressive therapy in kidney, heart, and liver transplant patients.

Generic Name
Muromonab
DrugBank Accession Number
DB00075
Background

Murine monoclonal antibody specific to CD3 T-cell lymphocyte antigens. More specifically it is a purified murine (mouse) monoclonal antibody, directed against the CD3 (T3) receptor on the surface of human T-cells (T-lymphocytes) cultured using the murine ascites method. Muromonab is 93% monomeric immune globulin G type 2a (IgG2a).

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Protein Chemical Formula
C6460H9946N1720O2043S56
Protein Average Weight
146189.7 Da
Sequences
>Muromonab-CD3 light chain
QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMNWYQQKSGTSPKRWIYDTSKLASGVPAH
FRGSGSGTSYSLTISGMEAEDAATYYCQQWSSNPFTFGSGTKLEINRADTAPTVSIFPPS
SEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTL
TKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC
>Muromonab-CD3 heavy chain
QVQLQQSGAELARPGASVKMSCKASGYTFTRYTMHWVKQRPGQGLEWIGYINPSRGYTNY
NQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYCARYYDDHYCLDYWGQGTTLTVSSA
KTTAPSVYPLAPVCGGTTGSSVTLGCLVKGYFPEPVTLTWNSGSLSSGVHTFPAVLQSDL
YTLSSSVTVTSSTWPSQSITCNVAHPASSTKVDKKIEPRPKSCDKTHTCPPCPAPELLGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN
STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE
LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW
QQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Download FASTA Format
Synonyms
  • Anti-CD3
  • Muromonab-CD3

Pharmacology

Indication

For treatment of organ transplant recipients, prevention of organ rejection

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofAcute renal allograft rejection•••••••••••••••••••••
Management ofSteroid resistant heart transplant rejection•••••••••••••••••••••
Management ofSteroid resistant hepatic transplant rejection•••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Used in organ transplant prophylaxis, Muromonab or OKT-3 binds specifically to the CD-3 complex, which is involved in antigen recognition and cell stimulation, on the surface of T lymphocytes. Immediately after administration CD-3-positive T lymphocytes are abruptly removed from circulation. It has been effective in reversing corticosteroid-resistant acute rejection in renal, liver, and cardiac transplant recipients.

Mechanism of action

Muromonab binds to the T-cell surface glycoprotein CD3 epsilon chain. It appears to kill CD-3 positive cells by inducing Fc mediated apoptosis, antibody mediated cytotoxicity and complement-dependent cytotoxicity.

TargetActionsOrganism
AT-cell surface glycoprotein CD3 delta chainNot AvailableHumans
AT-cell surface glycoprotein CD3 epsilon chain
binder
Humans
AT-cell surface glycoprotein CD3 gamma chainNot AvailableHumans
AT-cell surface glycoprotein CD3 zeta chainNot AvailableHumans
ULow affinity immunoglobulin gamma Fc region receptor III-BNot AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Most likely removed by opsonization via the reticuloendothelial system when bound to T lymphocytes, or by human antimurine antibody production

Route of elimination

Not Available

Half-life

0.8 hours (mammalian reticulocytes, in vitro)

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

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
AbataceptThe risk or severity of adverse effects can be increased when Muromonab is combined with Abatacept.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Muromonab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Muromonab.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Muromonab.
AducanumabThe risk or severity of adverse effects can be increased when Muromonab is combined with Aducanumab.
Food Interactions
No interactions found.

Products

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International/Other Brands
Orthoclone OKT3 (Janssen-Cilag)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Okt3Injection, solution5 mg/5mLIntravenousCentocor Ortho Biotech Products, L.P.1986-07-192011-07-30US flag
Orthoclone Okt 3 Sterile Solution IV 1mg/mlSolution1 mg / mLIntravenousJanssen Pharmaceuticals1987-12-312007-07-09Canada flag

Categories

ATC Codes
L04AA02 — Muromonab-cd3
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
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
JGA39ICE2V
CAS number
140608-64-6

References

General References
Not Available
KEGG Drug
D05092
PubChem Substance
46507837
RxNav
42405
ChEMBL
CHEMBL1201608
Therapeutic Targets Database
DAP001301
PharmGKB
PA164743097
Wikipedia
Muromonab-CD3

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Centocor Ortho Biotech Inc.
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous5 mg/5mL
SolutionIntravenous1 mg / mL
Prices
Unit descriptionCostUnit
Orthoclone okt-3 5 mg/5 ml261.75USD ml
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)61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
hydrophobicity-0.513Not Available
isoelectric point8.31Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
General Function
Transmembrane signaling receptor activity
Specific Function
The CD3 complex mediates signal transduction.
Gene Name
CD3D
Uniprot ID
P04234
Uniprot Name
T-cell surface glycoprotein CD3 delta chain
Molecular Weight
18929.38 Da
References
  1. Todd PA, Brogden RN: Muromonab CD3. A review of its pharmacology and therapeutic potential. Drugs. 1989 Jun;37(6):871-99. [Article]
  2. Wilde MI, Goa KL: Muromonab CD3: a reappraisal of its pharmacology and use as prophylaxis of solid organ transplant rejection. Drugs. 1996 May;51(5):865-94. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
General Function
Transmembrane signaling receptor activity
Specific Function
The CD3 complex mediates signal transduction, resulting in T cell activation and proliferation. Required for normal immune responses (PubMed:15546002, PubMed:8490660).
Gene Name
CD3E
Uniprot ID
P07766
Uniprot Name
T-cell surface glycoprotein CD3 epsilon chain
Molecular Weight
23147.09 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
General Function
Transmembrane signaling receptor activity
Specific Function
The CD3 complex mediates signal transduction.
Gene Name
CD3G
Uniprot ID
P09693
Uniprot Name
T-cell surface glycoprotein CD3 gamma chain
Molecular Weight
20469.335 Da
References
  1. Todd PA, Brogden RN: Muromonab CD3. A review of its pharmacology and therapeutic potential. Drugs. 1989 Jun;37(6):871-99. [Article]
  2. Wilde MI, Goa KL: Muromonab CD3: a reappraisal of its pharmacology and use as prophylaxis of solid organ transplant rejection. Drugs. 1996 May;51(5):865-94. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
General Function
Transmembrane signaling receptor activity
Specific Function
Probable role in assembly and expression of the TCR complex as well as signal transduction upon antigen triggering.
Gene Name
CD247
Uniprot ID
P20963
Uniprot Name
T-cell surface glycoprotein CD3 zeta chain
Molecular Weight
18696.275 Da
References
  1. Todd PA, Brogden RN: Muromonab CD3. A review of its pharmacology and therapeutic potential. Drugs. 1989 Jun;37(6):871-99. [Article]
  2. Wilde MI, Goa KL: Muromonab CD3: a reappraisal of its pharmacology and use as prophylaxis of solid organ transplant rejection. Drugs. 1996 May;51(5):865-94. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent...
Gene Name
FCGR3B
Uniprot ID
O75015
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor III-B
Molecular Weight
26215.64 Da
References
  1. Pellegrini P, Berghella AM, Del Beato T, Adorno D, Casciani CU: Immunological directives for biotherapy improvement in the treatment of colorectal cancer. Cancer Biother Radiopharm. 1996 Apr;11(2):113-8. [Article]
  2. Contasta I, Pellegrini P, Berghella AM, Del Beato T, Canossi A, Di Rocco M, Adorno D, Casciani CU: Necessity of biotherapeutic treatments inducing TH1 cell functions in colorectal cancer. Cancer Biother Radiopharm. 1996 Dec;11(6):373-83. [Article]

Drug created at June 13, 2005 13:24 / Updated at January 02, 2024 23:41