1. Anti-infection
  2. Bacterial
  3. IP6C

IP6C is a specific inhibitor and phage sensitizer targeting type II Thoeris systems. IP6C competitively binds to histidine in the catalytic pocket of ThsB, blocks the production of the His-ADPR alarm signal and inhibits ThsA activation, thereby relieving bacterial stasis of phage replication. IP6C selectively resensitizes drug-resistant bacteria carrying type II Thoeris systems (such as Pseudomonas aeruginosa) to phage lysis, without affecting other bacteria, and shows no toxicity to mice and human cell lines. IP6C significantly improves the survival rate of infected mice, and can be used to overcome bacterial phage defense mechanisms and study Pseudomonas aeruginosa infections.
Thoeris system: (named after the Egyptian goddess of fertility and protection), is a widespread anti-phage immune defense system in bacteria and archaea. Thoeris system belongs to the "Abortion Infection (Abi)" mechanism of bacteria: when an individual bacterium detects phage invasion, it initiates a suicide program and dies, thereby blocking phage replication and spread, and protecting the surrounding bacterial population from infection.

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IP6C

IP6C Chemical Structure

CAS No. : 103313-38-8

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Description

IP6C is a specific inhibitor and phage sensitizer targeting type II Thoeris systems. IP6C competitively binds to histidine in the catalytic pocket of ThsB, blocks the production of the His-ADPR alarm signal and inhibits ThsA activation, thereby relieving bacterial stasis of phage replication. IP6C selectively resensitizes drug-resistant bacteria carrying type II Thoeris systems (such as Pseudomonas aeruginosa) to phage lysis, without affecting other bacteria, and shows no toxicity to mice and human cell lines. IP6C significantly improves the survival rate of infected mice, and can be used to overcome bacterial phage defense mechanisms and study Pseudomonas aeruginosa infections[1].
Thoeris system: (named after the Egyptian goddess of fertility and protection), is a widespread anti-phage immune defense system in bacteria and archaea. Thoeris system belongs to the "Abortion Infection (Abi)" mechanism of bacteria: when an individual bacterium detects phage invasion, it initiates a suicide program and dies, thereby blocking phage replication and spread, and protecting the surrounding bacterial population from infection.

In Vitro

IP6C (0.1-1000 μM; 15 h) potently inhibits the type II BaY2 Thoeris anti-phage system in Bacillus subtilis, mediates bacterial lysis induced by SPO1 phage and restores phage propagation[1].
IP6C (500 μM; 4 h, 80 min) inhibits the type II BaY2 Thoeris system in Bacillus subtilis by blocking BaY2ThsB-mediated generation of the His-ADPR alarm signal, without affecting intracellular NAD+ levels[1].
IP6C (1 mM; 15 h) inhibits the type II MRSN11538 Thoeris anti-phage system in Pseudomonas aeruginosa PAO1 with an IC50 of 19 μM, thereby mediating Lit1 phage-induced bacterial lysis and restoring phage replicative capacity[1].
IP6C (300 μM; 8.5 h, 24 h) selectively re-sensitizes Pseudomonas aeruginosa PAO1 expressing the type II MRSN11538 Thoeris system to phage Lit1 in polymicrobial communities, reduces the titer of Pseudomonas aeruginosa, does not affect other bacterial species, and maintains stability in the community for 24 h[1].

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

Cell Proliferation Assay[1]

Cell Line: Bacillus subtilis
Concentration: 0.1-1000 μM
Incubation Time: 15 h
Result: Mediated SPO1 phage-induced bacterial lysis and restoring phage reproduction, with an IC50 of 10 μM against type II BaY2 Thoeris anti-phage system in Bacillus subtilis.
In Vivo

IP6C (50 mg/kg; i.p.; single dose) administered alongside Lit1 phage increases 7-day survival of Pseudomonas aeruginosa-infected BALB/c mice to 86%[1].

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

Animal Model: BALB/c (7-week-old, female)[1]
Dosage: 50 mg/kg
Administration: i.p.; single dose
Result: Increased 7-day survival rate to 86% when combined with Lit1 phage.
Showed 0% 7-day survival rate when administered alone.
Molecular Weight

161.16

Formula

C8H7N3O

CAS No.
SMILES

NC(C1=CN2C=CN=C2C=C1)=O

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

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  • 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.

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IP6C
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