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

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Pharmacology

Indication

For treatment of organ transplant recipients, prevention of organ rejection

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Associated Conditions

Indication Type	Indication	Approval Level	Dose Form
Management of	Acute renal allograft rejection	••••••••••••	•••••••••
Management of	Steroid resistant heart transplant rejection	••••••••••••	•••••••••
Management of	Steroid 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.

Target	Actions	Organism
AT-cell surface glycoprotein CD3 delta chain	Not Available	Humans
AT-cell surface glycoprotein CD3 epsilon chain	binder	Humans
AT-cell surface glycoprotein CD3 gamma chain	Not Available	Humans
AT-cell surface glycoprotein CD3 zeta chain	Not Available	Humans
ULow affinity immunoglobulin gamma Fc region receptor III-B	Not Available	Humans

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 Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

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.

Drug	Interaction
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Abatacept	The risk or severity of adverse effects can be increased when Muromonab is combined with Abatacept.
Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Muromonab.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Muromonab.
Adenovirus type 7 vaccine live	The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Muromonab.
Aducanumab	The 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

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Okt3	Injection, solution	5 mg/5mL	Intravenous	Centocor Ortho Biotech Products, L.P.	1986-07-19	2011-07-30
Orthoclone Okt 3 Sterile Solution IV 1mg/ml	Solution	1 mg / mL	Intravenous	Janssen Pharmaceuticals	1987-12-31	2007-07-09

Chemical Identifiers

UNII: JGA39ICE2V
CAS number: 140608-64-6

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-CD3

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
3	Active Not Recruiting	Treatment	Acute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative	1
3	Active Not Recruiting	Treatment	Recurrent B Acute Lymphoblastic Leukemia	1
3	Completed	Treatment	Type 1 Diabetes Mellitus	2
3	Not Yet Recruiting	Treatment	B-cell Acute Lymphoblastic Leukemia	1
3	Recruiting	Treatment	B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Centocor Ortho Biotech Inc.

Dosage Forms

Form	Route	Strength
Injection, solution	Intravenous	5 mg/5mL
Solution	Intravenous	1 mg / mL

Prices

Unit description	Cost	Unit
Orthoclone okt-3 5 mg/5 ml	261.75USD	ml

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

Patents

Not Available

Properties

State

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	61 °C (FAB fragment), 71 °C (whole mAb)	Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
hydrophobicity	-0.513	Not Available
isoelectric point	8.31	Not Available

Targets

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Details1. T-cell surface glycoprotein CD3 delta chain

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

Todd PA, Brogden RN: Muromonab CD3. A review of its pharmacology and therapeutic potential. Drugs. 1989 Jun;37(6):871-99. [Article]
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]

Details2. T-cell surface glycoprotein CD3 epsilon chain

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

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
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]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Details3. T-cell surface glycoprotein CD3 gamma chain

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

Todd PA, Brogden RN: Muromonab CD3. A review of its pharmacology and therapeutic potential. Drugs. 1989 Jun;37(6):871-99. [Article]
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]

Details4. T-cell surface glycoprotein CD3 zeta chain

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

Todd PA, Brogden RN: Muromonab CD3. A review of its pharmacology and therapeutic potential. Drugs. 1989 Jun;37(6):871-99. [Article]
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]

Details5. Low affinity immunoglobulin gamma Fc region receptor III-B

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

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]
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

Muromonab

Identification

Pharmacology

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References

Clinical Trials

Pharmacoeconomics

Properties

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References

References

References