NOD2 nucleotide binding oligomerization domain containing 2
ENSG00000167207 · protein coding · Open Targets profile
Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and plays an important role in gastrointestinal immunity (PubMed:12514169, PubMed:12527755, PubMed:12626759, PubMed:15044951, PubMed:15998797, PubMed:27283905, PubMed:27748583, PubMed:31649195). Specifically activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan found in every bacterial peptidoglycan type (PubMed:12514169, PubMed:12527755, PubMed:12626759, PubMed:12871942, PubMed:15044951, PubMed:15198989, PubMed:15998797, PubMed:22857257, PubMed:23322906, PubMed:27748583, PubMed:36002575). NOD2 specifically recognizes and binds 6-O-phospho- MDP, the phosphorylated form of MDP, which is generated by NAGK (PubMed:36002575). 6-O-phospho-MDP-binding triggers oligomerization that facilitates the binding and subsequent activation of the proximal adapter receptor-interacting RIPK2 (PubMed:11087742, PubMed:17355968, PubMed:21887730, PubMed:23806334, PubMed: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 (PubMed:11087742, PubMed:12514169, PubMed:12626759, PubMed:15198989, PubMed:21887730, PubMed:23322906, PubMed:23806334, PubMed:28436939). This in turn leads to the transcriptional activation of hundreds of genes involved in immune response (PubMed: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 (PubMed: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 (PubMed: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 (PubMed:27007849, PubMed:33942347). May also be involved in NLRP1 activation following activation by MDP, leading to CASP1 activation and IL1B release in macrophages (PubMed:18511561). {ECO:0000250|UniProtKB:Q8K3Z0, ECO:0000269|PubMed:11087742, ECO:0000269|PubMed:12514169, ECO:0000269|PubMed:12527755, ECO:0000269|PubMed:12626759, ECO:0000269|PubMed:12871942, ECO:0000269|PubMed:15044951, ECO:0000269|PubMed:15198989, ECO:0000269|PubMed:15998797, ECO:0000269|PubMed:17355968, ECO:0000269|PubMed:18511561, ECO:0000269|PubMed:19701189, ECO:0000269|PubMed:20637199, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:22857257, ECO:0000269|PubMed:23322906, ECO:0000269|PubMed:23806334, ECO:0000269|PubMed:27007849, ECO:0000269|PubMed:27283905, ECO:0000269|PubMed:27748583, ECO:0000269|PubMed:28436939, ECO:0000269|PubMed:31649195, ECO:0000269|PubMed:33942347, ECO:0000269|PubMed:36002575}.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, High-Quality Ligand, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.9461399912834167 (upper bound 1.1319999694824219). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 3 registry trials, updated in the last three years, of the most advanced drugs against NOD2 (mifamurtide), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Emanuela PalmeriniIstituto Ortopedico Rizzoli · 1 of 1 trials Phase 2+
- Nathalie GASPARGustave Roussy Cancer Campus · 1 of 1 trials Phase 2+
- Sophie PIPERNO-NEUMANNInstitut Curie · 1 of 1 trials Phase 2+
Registry trials of mifamurtide updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 3 of 3 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. Source: ClinicalTrials.gov, fetched live.
1 trials of drugs against NOD2 were stopped early
Terminated, withdrawn and suspended interventional trials of mifamurtide, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 1 most recent of 1.
- terminated · 2019-09-13 · University of Oxford · Mifamurtide“Failed to recruit sufficient numbers of patients in the funded period”
Paediatric incentives and obligations for NOD2's drugs
For mifamurtide: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · NOD2 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: no · No EMA paediatric investigation plan decision names mifamurtideRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/16/1699 positive 14 Jul 2016: Treatment of echinococcosis; EU/3/16/1700 positive 14 Jul 2016: Treatment of hepatocellular carcinomaRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Mepact: authorised since 6 Mar 2009Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA EPAR Mepact, 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of mifamurtideRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 4 interventional studies of mifamurtide include patients under 18; 2 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 1 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| MIFAMURTIDE | Small molecule | approval | osteosarcoma, neoplasm | Open Targets · ChEMBL |