osm-3 Antibody

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Description

OSM and Its Receptors: Biological Context

OSM binds to two receptor complexes:

  • Type I: gp130 + leukemia inhibitory factor receptor (LIFR)

  • Type II: gp130 + OSMRβ

These interactions activate signaling pathways such as JAK/STAT, MAPK, and PI3K/AKT, driving pro-inflammatory cytokine production, fibrosis, and tumor growth . OSM is implicated in RA, SSc, and cancers, where it promotes synovial fibroblast invasion, fibrotic tissue deposition, and metastasis .

Anti-OSM Antibodies

Antibody NameTargetMechanismKey FindingsClinical Status
GSK2330811OSMBinds OSM, blocking interaction with gp130Reduced STAT3 phosphorylation in RA synovial fluid; Phase 2 trial in SSc showed dose-dependent anemia/thrombocytopenia Discontinued due to safety concerns
SMI-10BOSMSmall molecule inhibitor (not antibody)Reduces STAT3 activation in cancer cells; preclinical efficacy Preclinical

Note: While anti-OSM antibodies like GSK2330811 neutralize OSM directly, their clinical utility is limited by on-target toxicities (e.g., hematologic effects) .

Anti-OSMRβ Antibodies

Antibody NameTargetMechanismPreclinical EfficacyClinical Status
B14/B21OSMRβDisrupts OSMR-IL6ST dimerization; promotes OSMR internalizationInhibited ovarian cancer growth (in vitro and in vivo); reduced STAT3 activation Preclinical
Anti-OSMR scFvsOSMRβBlocks OSMR-mediated STAT3 signalingSensitive cisplatin-resistant ovarian cancer to therapy Preclinical

Key Insight: Anti-OSMR antibodies show broader therapeutic potential by targeting the receptor rather than the cytokine, potentially avoiding systemic OSM suppression .

OSMR-STAT3 Axis in Cancer

  • Ovarian Cancer: OSMR overexpression correlates with metastasis and cisplatin resistance. Anti-OSMR antibodies (e.g., B14/B21) block STAT3 activation, reducing tumor growth and peritoneal dissemination .

  • Glioblastoma: OSMRβ knockdown suppresses STAT3-driven mesenchymal transition and tumor growth .

Fibrotic Diseases

In SSc, OSMRβ expression in fibroblasts and endothelial cells drives collagen deposition and vascular remodeling. Anti-OSM/OSMR strategies aim to disrupt this axis but face challenges in clinical translation .

Clinical Trials and Challenges

  • Bispecific Antibodies: Combining anti-OSMR with anti-PD-1/PD-L1 to enhance immunotherapy in cancers.

  • Biomarker-Driven Trials: Stratifying patients by OSMRβ expression levels to optimize therapeutic response .

Comparative Analysis of OSM-Targeting Strategies

StrategyAdvantagesLimitations
Anti-OSM (e.g., GSK2330811)Direct neutralization of cytokineSystemic OSM suppression; hematologic toxicity
Anti-OSMR (e.g., B14/B21)Tissue-specific targeting; preserves anti-inflammatory OSM rolesRequires OSMRβ expression in target tissues

Product Specs

Buffer
Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Form
Liquid
Lead Time
Made-to-order (14-16 weeks)
Synonyms
osm-3 antibody; M02B7.3 antibody; Osmotic avoidance abnormal protein 3 antibody; Kinesin-like protein osm-3 antibody
Target Names
osm-3
Uniprot No.

Target Background

Function
OSM-3 is a kinesin motor protein essential for anterograde intraflagellar transport (IFT) along the middle segment of sensory neuron cilia. It collaborates with the kinesin II motor complex (comprising klp-11, klp-20, and kap-1) and independently facilitates IFT along the distal segment. OSM-3 also plays a crucial role in regulating cilia length. It may further participate in neurogenesis and axonal transport.
Gene References Into Functions
  1. OSM-3 mutations result in both NPHP-4 dependent and independent phenotypes. PMID: 26863025
  2. Research findings indicate that kinesin-II and OSM-3 facilitate ciliary import and long-range transport. PMID: 26523365
  3. Dauer pheromone and gpa-3 signaling influence the coordination of intraflagellar transport of kinesin-II and OSM-3. PMID: 20501698
  4. OSM-3 functions as an accessory intraflagellar transport (IFT) kinesin motor; subtle modifications in its deployment or actions can contribute to variations in cilia morphology, cilia function, and sensory perception. PMID: 16492809
  5. Wild-type organisms exhibit the expression of an L1 (first larval stage) surface epitope in later larval stages when cultivated in spent culture medium. This expression is absent in chemotaxis-defective osm-3 mutants. PMID: 16879619
  6. Using a single-molecule fluorescence assay, researchers demonstrated that bacterially expressed OSM-3 in solution lacks processive movement and displays low microtubule-stimulated adenosine triphosphatase (ATPase) activity. PMID: 17000874

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Database Links

KEGG: cel:CELE_M02B7.3

STRING: 6239.M02B7.3b

UniGene: Cel.12541

Protein Families
TRAFAC class myosin-kinesin ATPase superfamily, Kinesin family, Kinesin II subfamily
Subcellular Location
Cytoplasm, cytoskeleton. Cell projection, cilium. Cytoplasm, cytoskeleton, cilium axoneme. Cytoplasm, cytoskeleton, cilium basal body.
Tissue Specificity
Expressed in an exclusive set of 26 chemosensory neurons whose dendritic endings are exposed to the external environment; six IL2 neurons of the inner labial sensilla, 8 pairs of amphid neurons in the head, and 2 pairs of phasmid neurons in the tail.

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