Customize ADM Antibody

Description

Antibody Types and Epitope Specificity

ADM antibodies include monoclonal and polyclonal variants, with distinct epitope targets:

Epitope Region	Antibody Example	Binding Amino Acids	Mechanism	Inhibition Efficacy
N-terminal	Adrecizumab	1–19 (human ADM)	Partial inhibition; redistributes ADM to circulation	24–25%
Midregional	MR-M	19–31 (mouse ADM)	Moderate inhibition	~70%
C-terminal	CT-M	40–50 (mouse ADM)	Full inhibition	100%

Key Insight: N-terminal antibodies (e.g., adrecizumab) increase circulating ADM levels while reducing interstitial vasodilation, enhancing endothelial barrier integrity .

Dual-Edged Effects of ADM

ADM has both protective and harmful roles in sepsis:

Beneficial: Enhances endothelial barrier function via cAMP/PKA pathways, reducing vascular leakage .
Detrimental: Causes hypotension via vasodilation .

ADM antibodies aim to preserve barrier-stabilizing effects while mitigating vasodilation.

Epitope-Dependent Outcomes

Antibody Type	Mechanism	Outcome
N-terminal (e.g., adrecizumab)	Binds ADM N-terminus → redistributes ADM to circulation → ↑ endothelial cAMP → ↓ vascular permeability	↑ Survival in sepsis models
C-terminal (e.g., CT-M)	Fully inhibits ADM signaling → ↓ vasodilation → ↑ blood pressure	Limited therapeutic benefit

Preclinical Data: In cecal ligation and puncture (CLP) models, N-terminal antibodies (e.g., NT-M) improved survival to 50% vs. 0% in controls .

Sepsis and Septic Shock

Adrecizumab (a humanized N-terminal antibody) is under investigation for sepsis:

Phase II Trial (NCT03085758): Targets patients with elevated bio-ADM levels.
Mechanism: ↑ Plasma ADM (bound to antibody) → ↑ endothelial barrier stability; ↓ interstitial ADM → ↓ vasodilation .
Safety: Well-tolerated with no severe adverse effects; terminal half-life ~14 days .

Anti-Inflammatory and Anti-Infective Roles

ADM antibodies may synergize with ADM’s intrinsic anti-inflammatory properties:

Pathways: cAMP/PKA → ↓ NF-κB → ↓ pro-inflammatory cytokines (e.g., TNFα, IL-6) .
Inflammatory Bowel Disease (IBD): Preclinical studies show reduced colitis severity with ADM therapy .

Balancing ADM’s Dual Roles

Complete inhibition (C-terminal antibodies) risks eliminating ADM’s barrier-protective effects, while partial inhibition (N-terminal) may optimize outcomes .

Personalized Medicine

Biomarker-guided therapy (e.g., bio-ADM levels) is critical for targeting patients most likely to benefit from ADM antibodies .

Product Specs

Buffer

Preservative: 0.03% ProClin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4

Form

Liquid

Lead Time

14-16 weeks (Made-to-order)

Synonyms

ADM antibody; At4g11940 antibody; F16J13.10Protein ADMETOS antibody

Target Names

ADM

Uniprot No.

Q9SZ59

Target Background

Function

This antibody targets a dosage-sensitive gene product crucial for maintaining balanced paternal and maternal gene expression in the endosperm. This balance is essential for proper seed development. The gene's function contributes to postzygotic reproductive isolation by inducing triploid seed arrest in a dosage-dependent manner, thus acting as a component of postzygotic interploidy hybridization barriers.

Gene References Into Functions

A genetic screen for suppressors of triploid seed abortion identified the paternally expressed imprinted gene ADMETOS (ADM). Increased ADM dosage causes triploid seed arrest. [ADMETOS] [ADM] PMID: 24012484

Database Links

KEGG: ath:AT4G11940

STRING: 3702.AT4G11940.1

UniGene: At.54287

Tissue Specificity

Paternally imprinted expression in the endosperm.

Q&A

ADM Antibody Research FAQs

Advanced Research Questions

How to resolve contradictions between in vitro potency and in vivo efficacy of ADM antibodies?
Example: NT-M antibodies show low in vitro cAMP inhibition (~25%) but reduce mortality by 73% in murine sepsis . Strategies include:
- Assessing antibody pharmacokinetics (e.g., Fab vs. F(ab)₂ fragments for tissue penetration) .
- Evaluating off-target effects using transcriptomics or proteomics.
- Testing in multiple disease models (e.g., sepsis vs. hypertension) to identify context-dependent mechanisms .
What methods ensure specificity and reproducibility of ADM antibodies in complex biological matrices?
- Validation steps:
  1. Confirm subcellular localization via immunofluorescence (e.g., endothelial cells for vascular studies) .
  2. Use immunodepletion assays to verify target binding in serum/plasma .
  3. Cross-test against related peptides (e.g., proadrenomedullin) to rule out cross-reactivity .
- Troubleshooting tip: Pre-adsorb antibodies with recombinant ADM to confirm signal loss .
How to mitigate immunogenicity risks when using ADM antibodies in preclinical models?
- Anti-drug antibody (ADA) assays: Employ bridging ELISA or electrochemiluminescence to detect ADA formation .
- Strategies:
  - Use fully humanized antibodies to reduce immunogenicity.
  - Monitor ADA incidence in long-term studies (>28 days) with serial sampling .

Table 1: Epitope-Specific Functional Profiles of Anti-ADM Antibodies

Epitope Region	Affinity Constant (M)	Maximal cAMP Inhibition	In Vivo Survival Benefit (CLP Model)
N-terminal	$1.6 \times 10^{-8}$	25%	73% reduction in mortality
Midregional	$4.2 \times 10^{-9}$	70%	40% reduction
C-terminal	$1.1 \times 10^{-9}$	100%	35% reduction

Methodological Challenges

How to design a robust sepsis model for testing ADM antibody efficacy?
- Key parameters:
  - Use cecal ligation and puncture (CLP) in C57Bl/6 mice with 14-day survival as the primary endpoint .
  - Administer antibodies intravenously at 0.2 mg/mL immediately post-surgery .
- Controls: Include unspecific IgG and vehicle groups to isolate antibody effects .
What are best practices for validating ADM antibody lot-to-lot consistency?
- Perform parallel testing of old/new lots in:
  1. Surface plasmon resonance (SPR) for binding kinetics.
  2. Functional assays (e.g., cAMP inhibition at IC₅₀).
  3. In vivo pilot studies (n=3–5 per group) to confirm reproducibility .

Ethical and Safety Considerations

What safety assessments are critical for ADM antibody studies?
- Acute toxicity: Administer 15-fold higher doses (3.0 mg/mL) in healthy mice; monitor survival and organ histology .
- Chronic effects: Assess autoimmunity markers (e.g., ANA titers) in 90-day repeated-dose studies.

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ADM Antibody