Identification

Name
Muromonab
Accession Number
DB00075  (BTD00005, BIOD00005)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

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).

Protein structure
Db00075
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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Okt3Injection, solution5 mg/5mLIntravenousCentocor Ortho Biotech Products, L.P.1986-07-192011-07-30Us
Orthoclone Okt 3 Sterile Solution IV 1mg/mlSolutionIntravenousJanssen Pharmaceuticals1987-12-312007-07-09Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Orthoclone OKT3 (Janssen-Cilag)
Categories
UNII
JGA39ICE2V
CAS number
140608-64-6

Pharmacology

Indication

For treatment of organ transplant recipients, prevention of organ rejection

Associated Conditions
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
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
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Muromonab is combined with 2-Methoxyethanol.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Muromonab is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
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.
AbetimusThe risk or severity of adverse effects can be increased when Muromonab is combined with Abetimus.
AbituzumabThe risk or severity of adverse effects can be increased when Muromonab is combined with Abituzumab.
AbrilumabThe risk or severity of adverse effects can be increased when Muromonab is combined with Abrilumab.
ActeosideThe risk or severity of adverse effects can be increased when Muromonab is combined with Acteoside.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Muromonab.
AdecatumumabThe risk or severity of adverse effects can be increased when Muromonab is combined with Adecatumumab.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D05092
PubChem Substance
46507837
RxNav
42405
ChEMBL
CHEMBL1201608
Therapeutic Targets Database
DAP001301
PharmGKB
PA164743097
Wikipedia
Muromonab
ATC Codes
L04AA02 — Muromonab-cd3

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentBrain and Central Nervous System Tumors1
1CompletedTreatmentMultiple Myeloma and Plasma Cell Neoplasm1
1RecruitingTreatmentRecurrent B Acute Lymphoblastic Leukemia / Recurrent Mixed Phenotype Acute Leukemia / Refractory B Acute Lymphoblastic Leukemia / Refractory Mixed Phenotype Acute Leukemia1
1RecruitingTreatmentRecurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma / Recurrent Burkitt Lymphoma / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Mediastinal Lymphoma / Recurrent Non-Hodgkin Lymphoma / Recurrent Small Lymphocytic Lymphoma / Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma / Refractory Burkitt Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory Follicular Lymphoma / Refractory Mantle Cell Lymphoma / Refractory Marginal Zone Lymphoma / Refractory Mediastinal Lymphoma / Refractory Non-Hodgkin's lymphoma / Refractory Small Lymphocytic Lymphoma1
1Unknown StatusTreatmentHealthy Volunteers1
1WithdrawnTreatmentMalignant Lymphomas1
1WithdrawnTreatmentMalignant Ovarian Clear Cell Tumor / Malignant Ovarian Serous Tumor / Recurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma / Stage IIIA Fallopian Tube Cancer / Stage IIIA Ovarian Cancer / Stage IIIA Primary Peritoneal Cancer / Stage IIIB Fallopian Tube Cancer / Stage IIIB Ovarian Cancer / Stage IIIB Primary Peritoneal Cancer / Stage IIIC Fallopian Tube Cancer / Stage IIIC Ovarian Cancer / Stage IIIC Primary Peritoneal Cancer / Stage IV Fallopian Tube Cancer / Stage IV Ovarian Cancer / Stage IV Primary Peritoneal Cancer1
1, 2CompletedTreatmentModerate to Severe Crohn's Disease1
1, 2CompletedTreatmentUlcerative Colitis1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemia Recurrent / CD19 Positive / Philadelphia Chromosome Positive / Refractory Acute Lymphoblastic Leukemia1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative / Leukemias / Untreated Adult Acute Lymphoblastic Leukemia1
1, 2Unknown StatusTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
2CompletedTreatmentAbdominal wall neoplasm / Fallopian Tube Neoplasms / Ovarian Cancer1
2CompletedTreatmentBrain and Central Nervous System Tumors1
2CompletedTreatmentGiant Cell Myocarditis / Myocarditis1
2CompletedTreatmentGraft Versus Host Disease (GVHD) / Leukemias / Myelodysplastic Syndromes1
2CompletedTreatmentHemoglobinuria, Paroxysmal Nocturnal (PNH) / Juvenile Myelomonocytic Leukemia (JMML) / Leukemia Acute Myeloid Leukemia (AML) / Leukemia, Acute Lymphocytic (ALL) / Leukemia, Myeloid, Chronic(CML) / Lymphoma, Hodgkins / Myelodysplastic Syndromes (MDS) / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentMalignant Melanoma of Skin / Melanoma (Skin)1
2CompletedTreatmentType 1 Diabetes Mellitus1
2RecruitingTreatmentAccelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Acute Lymphoblastic Leukaemia Recurrent / Acute Lymphoblastic Leukaemias (ALL) / Acute Myeloid Leukemia With BCR-ABL1 / Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Philadelphia Chromosome Positive / Refractory Acute Lymphoblastic Leukemia1
2RecruitingTreatmentAccelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Acute Lymphoblastic Leukaemia Recurrent / Acute Lymphoblastic Leukaemias (ALL) / BCR-ABL1 Fusion Protein Expression / Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic / Philadelphia Chromosome Positive / Refractory Acute Lymphoblastic Leukemia / T(9;22)1
2RecruitingTreatmentAcute Lymphoblastic Leukaemia Recurrent / Acute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia / B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / Refractory Acute Lymphoblastic Leukemia1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia / B Lymphoblastic Lymphoma / Leukemias1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemias / Philadelphia Chromosome Negative / Recurrent B Acute Lymphoblastic Leukemia / Refractory B Acute Lymphoblastic Leukemia1
2RecruitingTreatmentAcute Lymphocytic Leukemia (ALL) / Adult Acute Lymphoblastic Leukemia in Complete Remission / B Acute Lymphoblastic Leukemia / Leukemias / Minimal Residual Disease / Philadelphia Chromosome Positive1
2RecruitingTreatmentAdult B Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive1
2RecruitingTreatmentCastration Levels of Testosterone / Castration-Resistant Prostate Carcinoma / Prostate Carcinoma Metastatic in the Bone / PSA Progression / Stage IV Prostate Adenocarcinoma AJCC v71
2SuspendedTreatmentB Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative / Recurrent B Acute Lymphoblastic Leukemia / Refractory B Acute Lymphoblastic Leukemia1
2TerminatedTreatmentChronic Myeloproliferative Disorders / Graft Versus Host Disease (GVHD) / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes1
2Unknown StatusTreatmentChronic Hepatitis C Virus (HCV) Infection1
2Unknown StatusTreatmentRenal Cancers1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative1
3Active Not RecruitingTreatmentRecurrent B Acute Lymphoblastic Leukemia1
3CompletedTreatmentType 1 Diabetes Mellitus2
3RecruitingTreatmentB Acute Lymphoblastic Leukemia / B Lymphoblastic Lymphoma / Down Syndrome (DS)1
Not AvailableCompletedTreatmentMyocarditis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Centocor Ortho Biotech Inc.
Dosage forms
FormRouteStrength
Injection, solutionIntravenous5 mg/5mL
SolutionIntravenous
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

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
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. [PubMed:2503348]
  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. [PubMed:8861551]
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. [PubMed:17139284]
  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. [PubMed:17016423]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
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. [PubMed:2503348]
  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. [PubMed:8861551]
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. [PubMed:2503348]
  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. [PubMed:8861551]
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. [PubMed:10851527]
  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. [PubMed:10851498]

Drug created on June 13, 2005 07:24 / Updated on June 12, 2020 10:51

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