2. Immunology/Inflammation
  3. TREM receptor
  4. AL002

AL002 is a humanized monoclonal IgG1 antibody and a blood-brain barrier-permeable TREM2 modulator. AL002 binds to TREM2 on the surface of microglia, promotes TREM2 clustering and the formation of the TREM2-DAP12 complex, activates the TREM2 signaling pathway and PI3K cascade, and induces TREM2 internalization and degradation. AL002 is applicable to research related to Alzheimer's disease.

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AL002

AL002 Chemical Structure

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Description

AL002 is a humanized monoclonal IgG1 antibody and a blood-brain barrier-permeable TREM2 modulator. AL002 binds to TREM2 on the surface of microglia, promotes TREM2 clustering and the formation of the TREM2-DAP12 complex, activates the TREM2 signaling pathway and PI3K cascade, and induces TREM2 internalization and degradation. AL002 is applicable to research related to Alzheimer's disease[1][2].

Isotype

Human IgG1 kappa
Recommend Isotype Controls
Species Reactivity

Human
IC50 & Target

TREM-2

 

In Vitro

AL002 (0.0003-5 μg/mL, 48 h) reduces membrane-bound and soluble TREM2 levels in primary human macrophages, indicating TREM2 activation and internalization[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

AL002 Related Antibodies
Parmacokinetics
Species Dose Route Cmax AUC0-t CL
Cynomolgus Monkey[1] 20 mg/kg i.v. 504 μg/mL 33,700 μg·h/mL 0.615 mL/h/kg
Cynomolgus Monkey[1] 80 mg/kg i.v. 1560 μg/mL 99,400 μg·h/mL 0.811 mL/h/kg
Cynomolgus Monkey[1] 250 mg/kg i.v. 5130 μg/mL 265,000 μg·h/mL 0.976 mL/h/kg
In Vivo

AL002 (20-250 mg/kg; i.v.; once weekly or once monthly) dose-dependently engages TREM2 and activates downstream signaling pathways in healthy cynomolgus monkeys, with the 250 mg/kg weekly dose producing the most robust reductions in CSF sTREM2 and brain total TREM2, and increases in SPP1, CSF1R, and IL1RN[1].
AL002c (50 mg/kg; single dose) upregulates genes associated with TREM2 signaling in the frontal cortex of human TREM2-overexpressing transgenic mice[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Cambodia origin cynomolgus monkeys (24 to 50 months old, male/female); naive female cynomolgus monkeys (2-3 kg)[1]
Dosage: 20 mg/kg; 80 mg/kg; 250 mg/kg
Administration: i.v.; once weekly (5 doses for 4-week study; 3 doses for DRF study); once monthly (3 doses for interval study); 4-week recovery period for 250 mg/kg group
Result: Dose-dependently decreased CSF sTREM2: 20 mg/kg caused a partial reduction, while 80 and 250 mg/kg caused >70% reduction compared with predose levels.\nDose-dependently reduced total TREM2 protein in brain tissues: 250 mg/kg significantly reduced TREM2 in frontal cortex (p < 0.001) and hippocampus (p < 0.0001); 80 mg/kg significantly reduced TREM2 in hippocampus (p < 0.001); 20 mg/kg showed a non-significant reduction trend.\nDose-dependently increased frontal cortex SPP1 mRNA expression: 80 and 250 mg/kg had significantly higher levels than controls (ps < 0.01).\nElevated CSF SPP1 protein levels: 80 and 250 mg/kg showed increases 48 hours after Day 1 dose; 250 mg/kg caused statistically significant increases 12 and 24 hours after each monthly dose; 80 mg/kg showed partial, non-significant increases after monthly doses.\nIncreased frontal cortex CSF1R mRNA and protein: 250 mg/kg had significantly elevated CSF1R mRNA and protein (p < 0.05) compared with controls; lower doses showed non-significant trends.\nElevated CSF IL1RN protein levels: 80 and 250 mg/kg had significantly higher levels 48 hours after Day 1 dose and 48 hours after Day 29 dose (ps < 0.0001).
Animal Model: BAC transgenic mice overexpressing human TREM2[1]
Dosage: 50 mg/kg
Administration: single dose
Result: Upregulated expression of Tyrobp (Dap12), Csf1r, and Gfap genes in frontal cortex.
Gene ID

54209  [NCBI]

Accession
Application

ELISA, FACS, Functional assay
Conjugated

Unconjugated
Reconsititution

The product can be reconstituted/diluted with sterile PBS or saline.
Molecular Weight

145.62 kDa

Appearance

Liquid

Color

Colorless to light yellow

SMILES

[AL002]
Shipping

Shipping with dry ice.
Formulation

Please refer to the lot-specific COA for specific buffer information.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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AL002 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

AL002AL 002AL-002TREM receptorTriggering receptors expressed on myeloid cellsAβDAP12APOE ε4 carriershealthy volunteerscynomolgus monkeysPI3K cascadesAlzheimer’s diseaseTREM2primary human macrophagesmicroglialInhibitorinhibitorinhibit

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