Mifamurtide 4mg powder for dispersion for infusion vials
Prescription only
Requires a prescription from a doctor or prescriber
Mifamurtide is an immunomodulator with antitumor activity via activation of macrophages and monocytes.
Active ingredients:
Mifamurtide
1 safety notice
Safety information for pregnancy and breastfeeding
Pregnancy
Mifamurtide was not mutagenic and did not cause teratogenic effects in rats and rabbits.
Embryotoxic effects were observed only at maternal toxic levels.
Always consult your doctor or midwife before taking any medicine during pregnancy or while breastfeeding. Source: DrugBank (CC BY-NC 4.0).
Official documents, adverse reaction reporting, and safety monitoring
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Source: MHRA Products DatabaseOGL 3.0
Updated 3 months ago(16 Jan 2026)Safety monitoring data
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Mifamurtide 4mg powder for concentrate for dispersion for infusion vials
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Clinical guidelines and formulary information
British National Formulary
Mifamurtide
BNF
Drug monograph — bnf.nice.org.ukSource: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
NICE clinical guidance(1)
Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
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SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF codes from NHS Business Services Authority (NHSBSA). ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
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Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
None known
Half-life
0.40 hours
Mechanism
It was discovered that tumor necrosis could be promoted by factors released by the host’s immune system (e.
Food interactions
None known
Human targets
2 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
4.86 h
Due to rapid clearance from plasma, administration of mifamurtide is associated with a very low serum concentration of total (liposomal and free) drug.…
Half-life
4 mg
Following intravenous administration of 4 mg mifamurtide in healthy adult subjects, the half life was 2.05…
Volume of distribution
4 mg
The mean volume of distribution at steady state (Vss) of total mifamurtide ranged from 225 to 28.7…
Metabolism
Metabolism of liposomal MTP-PE has not been studied in humans .
[L1203]…
[L1203]…
Elimination
As there was no quantifiable urinary excretion of mifamurtide and renal impairment has no clinically significant impact on drug pharmacokinetics,…
Clearance
4 mg
The clearance from the plasma is rapid .
[L1203]
Following 4 mg intravenous infusion, the mean clearance rate of total mifamurtide in healthy subjects ranged from 565 to 569 mL/min .
[A31748]…
[L1203]
Following 4 mg intravenous infusion, the mean clearance rate of total mifamurtide in healthy subjects ranged from 565 to 569 mL/min .
[A31748]…
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
Mifamurtide is an immunomodulator with antitumor activity via activation of macrophages and monocytes. Also called L-MTP-PE, mifamurtide may be a liposomal form of of the active ingredient MTP-PE, which is a synthetic, less pyrogenic, and longer-acting derivative of muramyl dipeptide (MDP). MDP is a motif present in all gram-positive and gram-negative bacterial walls that is recognized by different signalling molecules and activators such as nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) and toll-like receptors present in macrophages and monocytes. The overall result of MDP recognition leads to the production of proinflammatory cytokines and promotion of bactericidal and tumoricidal effects [A31745]. As a liposomal formulation, mifamurtide demonstrates an enhanced tumoricidal effect and improved safety profile [A31745].
Mifamurtide is marketed in Europe as Mepact for intravenous infusion. It is administered as an adjuvant therapy to postoperative combination chemotherapy in pediatric, adolescent or adult patients with high-grade, resectable, non-metastatic osteosarcoma after macroscopically complete surgical resection. In the US, it is currently under investigation that holds orphan drug status for the treatment of osteosarcoma [A31746].
Osteosarcoma is the most common primary malignant bone tumor that usually arises in the metaphyses of long bone in children and adolescents [A31744]. The standard therapy for osteosarcoma is comprised of macroscopic surgical resection and multi-agent chemotherapy consisting of doxorubicin, cisplatin, high-dose methotrexate with leucovorin rescue, and ifosfamide [A31744]. While about 90% of patients with newly diagnosed osteosarcoma may achieve complete remission from first-line therapies, the prognosis is still poor for patients with non-metastatic osteosarcoma with lower 5-year event-free survival. In a large, randomized, open-label, multicenter, phase III trial, the treatment of mifamurtide in conjunction with three- or four-drug combination chemotherapy (doxorubicin, cisplatin, and high-dose methotrexate with, or without, ifosfamide) was associated with significant improvement in survival rates and good tolerance [A31746]. The adverse events (AEs) associated with mifamurtide were generally mild to moderate in severity [A31748].
Mifamurtide is marketed in Europe as Mepact for intravenous infusion. It is administered as an adjuvant therapy to postoperative combination chemotherapy in pediatric, adolescent or adult patients with high-grade, resectable, non-metastatic osteosarcoma after macroscopically complete surgical resection. In the US, it is currently under investigation that holds orphan drug status for the treatment of osteosarcoma [A31746].
Osteosarcoma is the most common primary malignant bone tumor that usually arises in the metaphyses of long bone in children and adolescents [A31744]. The standard therapy for osteosarcoma is comprised of macroscopic surgical resection and multi-agent chemotherapy consisting of doxorubicin, cisplatin, high-dose methotrexate with leucovorin rescue, and ifosfamide [A31744]. While about 90% of patients with newly diagnosed osteosarcoma may achieve complete remission from first-line therapies, the prognosis is still poor for patients with non-metastatic osteosarcoma with lower 5-year event-free survival. In a large, randomized, open-label, multicenter, phase III trial, the treatment of mifamurtide in conjunction with three- or four-drug combination chemotherapy (doxorubicin, cisplatin, and high-dose methotrexate with, or without, ifosfamide) was associated with significant improvement in survival rates and good tolerance [A31746]. The adverse events (AEs) associated with mifamurtide were generally mild to moderate in severity [A31748].
Properties:
solid
Avg. mass: 1277.52 Da
DrugBank indication
Indicated in children, adolescents and young adults for the treatment of high-grade, resectable, non-metastatic osteosarcoma after macroscopically complete surgical resection, typically in combination with post-operative multi-agent chemotherapy .
[L1203]
[L1203]
Also known as(6)
Mifamurtida
Mifamurtide
hToll
CARD15
Caspase recruitment domain-containing protein 15
Inflammatory bowel disease protein 1
Dosage forms(3)
Powder (Intravenous; Parenteral) — 4 MG
Injection (Parenteral) — 4 mg
Powder (Intravenous) — 4 mg
Molecular properties(19)
Drug interactions(133)
Known interactions with other medications. Always consult a healthcare professional.
Cyclosporine
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Cyclosporine.
Tacrolimus
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Tacrolimus.
Voclosporin
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Voclosporin.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Icosapent.
Indomethacin
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Indomethacin.
Nabumetone
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Nabumetone.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Ketorolac.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Tenoxicam.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Celecoxib.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Tolmetin.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Rofecoxib.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Piroxicam.
Fenoprofen
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Fenoprofen.
Valdecoxib
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Valdecoxib.
Diclofenac
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Diclofenac.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Sulindac.
Flurbiprofen
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Flurbiprofen.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Etodolac.
Mefenamic acid
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Mefenamic acid.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Naproxen.
Sulfasalazine
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Sulfasalazine.
Phenylbutazone
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Phenylbutazone.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Meloxicam.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Carprofen.
Diflunisal
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Diflunisal.
Salicylic acid
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Salicylic acid.
Meclofenamic acid
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Meclofenamic acid.
Acetylsalicylic acid
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Acetylsalicylic acid.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Oxaprozin.
Ketoprofen
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Ketoprofen.
Balsalazide
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Balsalazide.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Ibuprofen.
Lumiracoxib
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Lumiracoxib.
Magnesium salicylate
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Magnesium salicylate.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Salsalate.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Choline magnesium trisalicylate.
Antrafenine
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Antrafenine.
Aminophenazone
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Aminophenazone.
Antipyrine
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Antipyrine.
Tiaprofenic acid
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Tiaprofenic acid.
Etoricoxib
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Etoricoxib.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Taxifolin.
Oxyphenbutazone
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Oxyphenbutazone.
Licofelone
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Licofelone.
Nimesulide
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Nimesulide.
Benoxaprofen
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Benoxaprofen.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Zomepirac.
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Cimicoxib.
Lornoxicam
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Lornoxicam.
Aceclofenac
Moderate
The therapeutic efficacy of Mifamurtide can be decreased when used in combination with Aceclofenac.
Showing 50 of 133 interactions
Toxicity & overdose
There have been no reports of overdose with mifamurtide. Signs and symptoms that were associated with higher doses and/or were dose limiting were not life-threatening, and included fever, chills, fatigue, nausea, vomiting, headache and hypotension or hypertension .
[L1203]
In cases of suspected overdose, appropriate supportive care is recommended. Gastrointestinal toxicity associated with nausea, vomiting and loss of apetite from mifamurtide therapy is commonly observed.
Mifamurtide was not mutagenic and did not cause teratogenic effects in rats and rabbits.
Embryotoxic effects were observed only at maternal toxic levels. There is no evidence of mifamurtide generating harmful effects on male or female reproductive organs. Studies assessing reproductive function, perinatal toxicity and carcinogenicity have not been performed .
[L1203]
[L1203]
In cases of suspected overdose, appropriate supportive care is recommended. Gastrointestinal toxicity associated with nausea, vomiting and loss of apetite from mifamurtide therapy is commonly observed.
Mifamurtide was not mutagenic and did not cause teratogenic effects in rats and rabbits.
Embryotoxic effects were observed only at maternal toxic levels. There is no evidence of mifamurtide generating harmful effects on male or female reproductive organs. Studies assessing reproductive function, perinatal toxicity and carcinogenicity have not been performed .
[L1203]
How it works
Mechanism of action
It was discovered that tumor necrosis could be promoted by factors released by the host’s immune system (e.g. macrophages) in response to the endotoxins or bacterial products [A31745]. Mifamurtide is referred to as MTP-PE or L-MTP-PE (in case of the liposomal formulation), which is a fully synthetic derivative of muramyl dipeptide (MDP), which is a motif within the peptidoglycan polymer in the cell wall of bacteria.
MDP stimulates the immune system by being recognized by different pattern recognition molecules and receptors, such as nucleotide-binding oligomerization domain (NOD) 2 receptor and toll-like receptor (TLR). Similarly, mifamurtide acts as a ligand for TRL4 and NOD2. Involved in the innate immunity, NOD2 is an intracellular MDP sensor that is primarily expressed on monocytes, dendritic cells, and macrophages. It possesses an amino-terminal caspase recruitment domain, which is required to trigger nuclear factor-kappaB (NF-κB) signaling [A31745]. Activation of intracellular signaling transduction pathway NF-κB can promote inflammation and release of antimicrobial peptides, resulting in the production of pro-inflammatory cytokines like interleukin-1β (IL-1β), interleukin-6 (IL-6), and TNF-α, and other molecules such as chemokines and adhesion molecules [A31745]. Upon binding to TLR4, mifamurtide may activate extracellular-signal-regulated kinase 1/2 (ERK 1/2), nuclear factor-kappa B (NF-κB) and adaptor protein (AP)-1 [A31744]. Mifamurtide may also activate NLRP3, which is an essential component of the inflammasome, a protein complex that promotes the cleavage of procaspase 1 into its active form. Active caspase 1 further activates pro-inflammatory cytokines like IL-1β [A31745]. Furthermore, mifamurtide induces the expression of adhesion molecules including lymphocyte function-associated antigen (LFA)-1, intracellular adhesion molecule (ICAM)-1, and human leukocyte antigen (HLA)-DR [A31744]. Mifamurtide may interact with interferon (IFN)-γ to up-regulate tumoricidal activity [A31744].
Upon intravenous administration, lipophilic mifamurtide is selectively phagocytosed by monocytes and macrophages followed by subsequent degradation of liposomal vesicles by the phagocytic cells. Then, MTP-PE is released into the cytosol where it interacts with Nod2 and activates the macrophages and monocytes [A31744]. Mifamurtide exerts a tumoricidal action via the same signalling pathway as MDP but with greater superiority because the lipophilic properties of MTP-PE cause higher cell uptake via passive transfer through the cytoplasmic membrane [A31744]. Incorporation of MTP-PE into liposomal structures allows better safety profile and more efficient distribution to the liver, spleen, and lungs after intravenous administration [A31744].
MDP stimulates the immune system by being recognized by different pattern recognition molecules and receptors, such as nucleotide-binding oligomerization domain (NOD) 2 receptor and toll-like receptor (TLR). Similarly, mifamurtide acts as a ligand for TRL4 and NOD2. Involved in the innate immunity, NOD2 is an intracellular MDP sensor that is primarily expressed on monocytes, dendritic cells, and macrophages. It possesses an amino-terminal caspase recruitment domain, which is required to trigger nuclear factor-kappaB (NF-κB) signaling [A31745]. Activation of intracellular signaling transduction pathway NF-κB can promote inflammation and release of antimicrobial peptides, resulting in the production of pro-inflammatory cytokines like interleukin-1β (IL-1β), interleukin-6 (IL-6), and TNF-α, and other molecules such as chemokines and adhesion molecules [A31745]. Upon binding to TLR4, mifamurtide may activate extracellular-signal-regulated kinase 1/2 (ERK 1/2), nuclear factor-kappa B (NF-κB) and adaptor protein (AP)-1 [A31744]. Mifamurtide may also activate NLRP3, which is an essential component of the inflammasome, a protein complex that promotes the cleavage of procaspase 1 into its active form. Active caspase 1 further activates pro-inflammatory cytokines like IL-1β [A31745]. Furthermore, mifamurtide induces the expression of adhesion molecules including lymphocyte function-associated antigen (LFA)-1, intracellular adhesion molecule (ICAM)-1, and human leukocyte antigen (HLA)-DR [A31744]. Mifamurtide may interact with interferon (IFN)-γ to up-regulate tumoricidal activity [A31744].
Upon intravenous administration, lipophilic mifamurtide is selectively phagocytosed by monocytes and macrophages followed by subsequent degradation of liposomal vesicles by the phagocytic cells. Then, MTP-PE is released into the cytosol where it interacts with Nod2 and activates the macrophages and monocytes [A31744]. Mifamurtide exerts a tumoricidal action via the same signalling pathway as MDP but with greater superiority because the lipophilic properties of MTP-PE cause higher cell uptake via passive transfer through the cytoplasmic membrane [A31744]. Incorporation of MTP-PE into liposomal structures allows better safety profile and more efficient distribution to the liver, spleen, and lungs after intravenous administration [A31744].
Pharmacodynamics
Mifamurtide stimulates the innate immunity by activating monocytes and macrophages. Within hours following administration of mifamurtide in healthy adults or patients with osteosarcoma NOS, elevated plasma levels of proinflammatory molecules, such as TNF-α, IL-6, and IL-1β, and other indicators of immune stimulation like C-reactive protein and neopterine were observed [A31745]. In vivo administration of mifamurtide in rat and mouse model resulted in inhibition of tumour growth of lung metastasis, skin and liver cancer, and fibrosarcoma [L1203]. In addition, increased disease-free survival rate was demonstrated when mifamurtide was given as an adjuvant in dog models of osteosarcoma and hemangiosarcoma. Administration of mifamurtide was associated with transient neutropenia, usually when used in conjunction with chemotherapy. Pronounced inflammatory responses are uncommon [L1203].
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
Due to rapid clearance from plasma, administration of mifamurtide is associated with a very low serum concentration of total (liposomal and free) drug. The mean AUC was 17.0 ± 4.86 h x nM and peak plasma concentration (Cmax) was 15.7 ± 3.72 nM following intravenous administration of 4 mg mifamurtide in healthy adult subjects .
[L1203]
Variability in AUC and Cmax is reported to be low .
[A31748]
[L1203]
Variability in AUC and Cmax is reported to be low .
[A31748]
Half-life
Following intravenous administration of 4 mg mifamurtide in healthy adult subjects, the half life was 2.05 ± 0.40 hours. In pediatric and adult patients with psteosarcoma, the half life was 2.04 ± 0.456 hours after intravenous infusion of 2 mg/m^2 .
[L1203]
[L1203]
Volume of distribution
The mean volume of distribution at steady state (Vss) of total mifamurtide ranged from 225 to 28.7 healthy subjects after 4 mg intravenous infusion .
[A31748]
There is no evidence of accumulation of L-MTP-PE or free MTP-PE (non-liposome-associated) .
[A31745]
[A31748]
There is no evidence of accumulation of L-MTP-PE or free MTP-PE (non-liposome-associated) .
[A31745]
Metabolism
Metabolism of liposomal MTP-PE has not been studied in humans .
[L1203]
The liposomes are mainly phagocytosed by the cells of the reticuloendothelial system (RES) .
[A31745]
[L1203]
The liposomes are mainly phagocytosed by the cells of the reticuloendothelial system (RES) .
[A31745]
Route of elimination
As there was no quantifiable urinary excretion of mifamurtide and renal impairment has no clinically significant impact on drug pharmacokinetics, renal clearance is not expected to contribute to the total systemic clearance of mifamurtide .
[A31748]
[A31748]
Clearance
The clearance from the plasma is rapid .
[L1203]
Following 4 mg intravenous infusion, the mean clearance rate of total mifamurtide in healthy subjects ranged from 565 to 569 mL/min .
[A31748]
[L1203]
Following 4 mg intravenous infusion, the mean clearance rate of total mifamurtide in healthy subjects ranged from 565 to 569 mL/min .
[A31748]
Drug targets(2)
Proteins and enzymes this drug interacts with in the body
Toll-like receptor 4
TLR4
ligand
Specific functionamyloid-beta binding
Cellular location
Cell membrane
General function & pharmacology
Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways .
PMID:10835634 PMID:15809303 PMID:16622205 PMID:17292937 PMID:17478729 PMID:20037584 PMID:20711192 PMID:23880187 PMID:27022195 PMID:29038465 PMID:17803912
At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) .
PMID:27022195
Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+) .
PMID:20711192
Mechanistically, acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response .
PMID:10835634 PMID:21393102 PMID:27022195 PMID:36945827 PMID:9237759
Alternatively, CD14-mediated TLR4 internalization via endocytosis is associated with the initiation of a MYD88-independent signaling via the TICAM1-TBK1-IRF3 axis leading to type I interferon production .
PMID:14517278
In addition to the secretion of proinflammatory cytokines, initiates the activation of NLRP3 inflammasome and formation of a positive feedback loop between autophagy and NF-kappa-B signaling cascade .
PMID:32894580
In complex with TLR6, promotes inflammation in monocytes/macrophages by associating with TLR6 and the receptor CD86 .
PMID:23880187
Upon ligand binding, such as oxLDL or amyloid-beta 42, the TLR4:TLR6 complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway .
PMID:23880187
In myeloid dendritic cells, vesicular stomatitis virus glycoprotein G but not LPS promotes the activation of IRF7, leading to type I IFN production in a CD14-dependent manner .
PMID:15265881 PMID:23880187
Required for the migration-promoting effects of ZG16B/PAUF on pancreatic cancer cells
PMID:10835634 PMID:15809303 PMID:16622205 PMID:17292937 PMID:17478729 PMID:20037584 PMID:20711192 PMID:23880187 PMID:27022195 PMID:29038465 PMID:17803912
At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) .
PMID:27022195
Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+) .
PMID:20711192
Mechanistically, acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response .
PMID:10835634 PMID:21393102 PMID:27022195 PMID:36945827 PMID:9237759
Alternatively, CD14-mediated TLR4 internalization via endocytosis is associated with the initiation of a MYD88-independent signaling via the TICAM1-TBK1-IRF3 axis leading to type I interferon production .
PMID:14517278
In addition to the secretion of proinflammatory cytokines, initiates the activation of NLRP3 inflammasome and formation of a positive feedback loop between autophagy and NF-kappa-B signaling cascade .
PMID:32894580
In complex with TLR6, promotes inflammation in monocytes/macrophages by associating with TLR6 and the receptor CD86 .
PMID:23880187
Upon ligand binding, such as oxLDL or amyloid-beta 42, the TLR4:TLR6 complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway .
PMID:23880187
In myeloid dendritic cells, vesicular stomatitis virus glycoprotein G but not LPS promotes the activation of IRF7, leading to type I IFN production in a CD14-dependent manner .
PMID:15265881 PMID:23880187
Required for the migration-promoting effects of ZG16B/PAUF on pancreatic cancer cells
Nucleotide-binding oligomerization domain-containing protein 2
NOD2
ligand
Specific functionactin binding
Cellular location
Cell membrane
General function & pharmacology
Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and plays an important role in gastrointestinal immunity .
PMID:12514169 PMID:12527755 PMID:12626759 PMID:15044951 PMID:15998797 PMID:27283905 PMID:27748583 PMID:31649195
Specifically activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan found in every bacterial peptidoglycan type .
PMID:12514169 PMID:12527755 PMID:12626759 PMID:12871942 PMID:15044951 PMID:15198989 PMID:15998797 PMID:22857257 PMID:23322906 PMID:27748583 PMID:36002575
NOD2 specifically recognizes and binds 6-O-phospho-MDP, the phosphorylated form of MDP, which is generated by NAGK .
PMID:36002575
6-O-phospho-MDP-binding triggers oligomerization that facilitates the binding and subsequent activation of the proximal adapter receptor-interacting RIPK2 .
PMID:11087742 PMID:17355968 PMID:21887730 PMID:23806334 PMID:28436939
Following recruitment, RIPK2 undergoes 'Met-1'- (linear) and 'Lys-63'-linked polyubiquitination by E3 ubiquitin-protein ligases XIAP, BIRC2, BIRC3 and the LUBAC complex, becoming a scaffolding protein for downstream effectors, triggering activation of the NF-kappa-B and MAP kinases signaling .
PMID:11087742 PMID:12514169 PMID:12626759 PMID:15198989 PMID:21887730 PMID:23322906 PMID:23806334 PMID:28436939
This in turn leads to the transcriptional activation of hundreds of genes involved in immune response .
PMID:15198989
Its ability to detect bacterial MDP plays a central role in maintaining the equilibrium between intestinal microbiota and host immune responses to control inflammation (By similarity). An imbalance in this relationship results in dysbiosis, whereby pathogenic bacteria prevail on commensals, causing damage in the intestinal epithelial barrier as well as allowing bacterial invasion and inflammation (By similarity). Acts as a regulator of appetite by sensing MDP in a subset of brain neurons: microbiota-derived MDP reach the brain, where they bind and activate NOD2 in inhibitory hypothalamic neurons, decreasing neuronal activity, thereby regulating satiety and body temperature (By similarity).
NOD2-dependent MDP-sensing of bacterial cell walls in the intestinal epithelial compartment contributes to sustained postnatal growth upon undernutrition (By similarity). Also plays a role in antiviral response by acting as a sensor of single-stranded RNA (ssRNA) from viruses: upon ssRNA-binding, interacts with MAVS, leading to activation of interferon regulatory factor-3/IRF3 and expression of type I interferon .
PMID:19701189
Also acts as a regulator of autophagy in dendritic cells via its interaction with ATG16L1, possibly by recruiting ATG16L1 at the site of bacterial entry .
PMID:20637199
NOD2 activation in the small intestine crypt also contributes to intestinal stem cells survival and function: acts by promoting mitophagy via its association with ATG16L1 (By similarity). In addition to its main role in innate immunity, also regulates the adaptive immune system by acting as regulator of helper T-cell and regulatory T-cells (Tregs) (By similarity).
Besides recognizing pathogens, also involved in the endoplasmic reticulum stress response: acts by sensing and binding to the cytosolic metabolite sphingosine-1-phosphate generated in response to endoplasmic reticulum stress, initiating an inflammation process that leads to activation of the NF-kappa-B and MAP kinases signaling .
PMID:27007849 PMID:33942347
May also be involved in NLRP1 activation following activation by MDP, leading to CASP1 activation and IL1B release in macrophages PMID:18511561
PMID:12514169 PMID:12527755 PMID:12626759 PMID:15044951 PMID:15998797 PMID:27283905 PMID:27748583 PMID:31649195
Specifically activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan found in every bacterial peptidoglycan type .
PMID:12514169 PMID:12527755 PMID:12626759 PMID:12871942 PMID:15044951 PMID:15198989 PMID:15998797 PMID:22857257 PMID:23322906 PMID:27748583 PMID:36002575
NOD2 specifically recognizes and binds 6-O-phospho-MDP, the phosphorylated form of MDP, which is generated by NAGK .
PMID:36002575
6-O-phospho-MDP-binding triggers oligomerization that facilitates the binding and subsequent activation of the proximal adapter receptor-interacting RIPK2 .
PMID:11087742 PMID:17355968 PMID:21887730 PMID:23806334 PMID:28436939
Following recruitment, RIPK2 undergoes 'Met-1'- (linear) and 'Lys-63'-linked polyubiquitination by E3 ubiquitin-protein ligases XIAP, BIRC2, BIRC3 and the LUBAC complex, becoming a scaffolding protein for downstream effectors, triggering activation of the NF-kappa-B and MAP kinases signaling .
PMID:11087742 PMID:12514169 PMID:12626759 PMID:15198989 PMID:21887730 PMID:23322906 PMID:23806334 PMID:28436939
This in turn leads to the transcriptional activation of hundreds of genes involved in immune response .
PMID:15198989
Its ability to detect bacterial MDP plays a central role in maintaining the equilibrium between intestinal microbiota and host immune responses to control inflammation (By similarity). An imbalance in this relationship results in dysbiosis, whereby pathogenic bacteria prevail on commensals, causing damage in the intestinal epithelial barrier as well as allowing bacterial invasion and inflammation (By similarity). Acts as a regulator of appetite by sensing MDP in a subset of brain neurons: microbiota-derived MDP reach the brain, where they bind and activate NOD2 in inhibitory hypothalamic neurons, decreasing neuronal activity, thereby regulating satiety and body temperature (By similarity).
NOD2-dependent MDP-sensing of bacterial cell walls in the intestinal epithelial compartment contributes to sustained postnatal growth upon undernutrition (By similarity). Also plays a role in antiviral response by acting as a sensor of single-stranded RNA (ssRNA) from viruses: upon ssRNA-binding, interacts with MAVS, leading to activation of interferon regulatory factor-3/IRF3 and expression of type I interferon .
PMID:19701189
Also acts as a regulator of autophagy in dendritic cells via its interaction with ATG16L1, possibly by recruiting ATG16L1 at the site of bacterial entry .
PMID:20637199
NOD2 activation in the small intestine crypt also contributes to intestinal stem cells survival and function: acts by promoting mitophagy via its association with ATG16L1 (By similarity). In addition to its main role in innate immunity, also regulates the adaptive immune system by acting as regulator of helper T-cell and regulatory T-cells (Tregs) (By similarity).
Besides recognizing pathogens, also involved in the endoplasmic reticulum stress response: acts by sensing and binding to the cytosolic metabolite sphingosine-1-phosphate generated in response to endoplasmic reticulum stress, initiating an inflammation process that leads to activation of the NF-kappa-B and MAP kinases signaling .
PMID:27007849 PMID:33942347
May also be involved in NLRP1 activation following activation by MDP, leading to CASP1 activation and IL1B release in macrophages PMID:18511561
Scientific references(4)
Ando K., Mori K., Corradini N., Redini F., Heymann D.
Mifamurtide for the treatment of nonmetastatic osteosarcoma.
Expert Opinion on Pharmacotherapy
2011 Feb12(2):285-92. doi: 10.1517/14656566.2011.543129
Kager L., Potschger U., Bielack S.
Review of mifamurtide in the treatment of patients with osteosarcoma. Therapeutics and Clinical Risk Management. 2010;:279. doi: 10.
2147/tcrm
s5688
Frampton J.E.
Mifamurtide: a review of its use in the treatment of osteosarcoma.
Paediatr Drugs
2010 Jun12(3):141-53. doi: 10.2165/11204910-000000000-00000
Venkatakrishnan K., Liu Y., Noe D., Mertz J., Bargfrede M., Marbury T., Farbakhsh K., Oliva C., Milton A.
Pharmacokinetics and pharmacodynamics of liposomal mifamurtide in adult volunteers with mild or moderate hepatic impairment.
British Journal of Clinical Pharmacology
2014 Jun77(6):998-1010. doi: 10.1111/bcp.12261
ATC classification(1 code)
ATC L03AX15
Affected organisms(1)
Humans and other mammals
Commercial products(1)
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Show
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Mifamurtide
Additional database identifiers
ChemSpider
32700228
HUGO Gene Nomenclature Committee (HGNC)
HGNC:11850
GenAtlas
TLR4
GeneCards
TLR4
GenBank Gene Database
U93091
Guide to Pharmacology
1754
UniProt Accession
TLR4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:5331
GeneCards
NOD2
Guide to Pharmacology
1763
UniProt Accession
NOD2_HUMAN
DrugBank citations
If you use DrugBank data in your research, please cite the following publications:
Knox C., Wilson M., Klinger C.M., et al
DrugBank 6.
0: the DrugBank Knowledgebase for 2024
Nucleic Acids Res. 2024 Jan 552(D1):D1265-D1275
Wishart D.S., Feunang Y.D., Guo A.C., et al
DrugBank 5.
0: a major update to the DrugBank database for 2018
Nucleic Acids Res. 2017 Nov 846(D1):D1074-D1082
Show earlier publications
Law V., Knox C., Djoumbou Y., et al
DrugBank 4.
0: shedding new light on drug metabolism
Nucleic Acids Res. 2014 Jan 142(1):D1091-7
Knox C., Law V., Jewison T., et al
DrugBank 3.
0: a comprehensive resource for 'omics' research on drugs
Nucleic Acids Res. 2011 Jan39(Database issue):D1035-41
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a knowledgebase for drugs, drug actions and drug targets.
Nucleic Acids Research
2008 Jan36(Database issue):D901-6
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a comprehensive resource for in silico drug discovery and exploration.
Nucleic Acids Research
2006 Jan 134(Database issue):D668-72
Source: go.drugbank.comCC BY-NC 4.0
Updated 26 days ago(8 Mar 2026)