1. Immunology/Inflammation Anti-infection
  2. Toll-like Receptor (TLR) Bacterial
  3. NAB815

NAB815 is a specific inhibitor of the Stx2a (Kd = 0.01 μM)/TLR4 interaction. NAB815 inhibits the neutrophil/Stx2a interaction (IC50 = 0.057 μg/mL). NAB815 inhibits the formation of Stx2-containing extracellular vesicles (EVs) produced by leukocytes and platelets and reduces their toxic effects in cellular (Vero cells) and animal models (CD-1 mice). NAB815 reduces bacterial loads in the kidneys, urine, and bladders of Escherichia coli-infected mice. NAB815 is useful in the study of hemolytic uremic syndrome (HUS).

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NAB815

NAB815 Chemical Structure

CAS No. : 1969250-99-4

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Description

NAB815 is a specific inhibitor of the Stx2a (Kd = 0.01 μM)/TLR4 interaction. NAB815 inhibits the neutrophil/Stx2a interaction (IC50 = 0.057 μg/mL). NAB815 inhibits the formation of Stx2-containing extracellular vesicles (EVs) produced by leukocytes and platelets and reduces their toxic effects in cellular (Vero cells) and animal models (CD-1 mice). NAB815 reduces bacterial loads in the kidneys, urine, and bladders of Escherichia coli-infected mice. NAB815 is useful in the study of hemolytic uremic syndrome (HUS)[1][2].

In Vitro

NAB815 (1 nM, 4 h) inhibits the formation of white blood cell/platelet aggregates by Stx2a[1].
NAB815 (0.01-0.1 μg/mL, 4 h) slightly affects the viability of human leukocytes but has no effect on erythrocytes, inhibits the formation of platelet-derived and leukocyte-derived pathogenic EVs containing Stx2a, impairs the recruitment of complement factors in Stx2-induced EVs[1].
NAB815 (0.01 μg/mL) affords protection against toxicity induced by Stx2a-triggered EVs in Vero cells[1].

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

In Vivo

NAB815 (0.01 μg/mL, 100 μL, i.v., once) affords protection against free Stx2a in CD-1 mice[1].
NAB815 (0.01 μg/mL, 300 μL, i.v., once) affords protection against EV-associated Stx2a in Human EVs CD-1 mice[1].
NAB815 (0.5-2 mg/L, 0.2 mL, s.c., twice a day, 3 days) reduces the bacterial burden in the kidney, urine and bladder in E. coli-infected female OF-1 mice[2].

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

Animal Model: CD-1 mice(6-7 weeks old 21-26 g, female) intoxicated with Stx2a (10 and 15 pg/g) [1]
Dosage: 0.01 μg/mL, 100 μL
Administration: i.v., once
Result: Improved survival rate without changing body weight, decreased intestinal damage.
Animal Model: Human EVs (10,400–20,800 g) CD-1 mice(6-7 weeks old 21-26 g, female) intoxicated with Stx2a (10 and 15 pg/g)[1]
Dosage: 0.01 μg/mL, 300 μL
Administration: i.v., once
Result: Decreased serum creatinine and a significant rise in serum urea, number of cells with acute tubular injuries (ATIs).
Animal Model: E. coli-infected (5 × 108) female OF-1 mice (27-33 g)[2]
Dosage: 0.5, 2, 2 mg/L, 0.2 mL
Administration: s.c., twice a day, 3 days
Result: Reduced CFU levels.
Molecular Weight

1175.42

Formula

C55H94N14O14

CAS No.
Sequence

Octanoic-{Dab}-Thr-{d-Thr}-{Dab}-{Dab}-{d-Phe}-Leu-{Abu}-{Dab}-Thr (lactam bridge: Dab4-Thr10)

Sequence Shortening

Octanoic-{Dab}-T-{d-Thr}-{Dab}-{Dab}-{d-Phe}-L-{Abu}-{Dab}-T (lactam bridge: Dab4-Thr10)

SMILES

O=C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@@](C(NCC[C@@H](C(N[C@H](C(N1)=O)CCN)=O)NC([C@@H]([C@@H](O)C)NC([C@H]([C@H](O)C)NC([C@H](CCN)NC(CCCCCCC)=O)=O)=O)=O)=O)([H])[C@H](O)C)=O)CCN)=O)CC)=O)CC(C)C)[C@H]1CC2=CC=CC=C2

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Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation
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    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.

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NAB815
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