T6167923 targets the MyD88 (Myeloid differentiation primary response 88) adaptor protein. It directly binds to the Toll/IL-1 receptor (TIR) domain of MyD88 and disrupts MyD88 homodimerization . The compound inhibits pro-inflammatory cytokines with the following IC50 values in peripheral blood mononuclear cells: IFN-γ (2.7 μM), IL-1β (2.9 μM), IL-6 (2.66 μM), and TNF-α (2.66 μM) .
T6167923 targets the MyD88 protein, an adaptor molecule in Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways. By binding to the TIR domain, it prevents MyD88 homodimerization and downstream signaling.

In peripheral blood mononuclear cells, T6167923 (0-500 μM; 20 h) suppresses the pro-inflammatory cytokine response to staphylococcal enterotoxin B (SEB) [2]. In HEK 293T cells, T6167923 (10-500 μM; 2 hours) suppresses the production of secreted alkaline phosphatase (SEAP) [2]. T6167923 (100 μM; 16 hours) decreases the inhibitory effect on MyD88 signaling by binding to TIR proteins [2]. T6167923 (1-500 μM; 13 hours) prevents the production of full-length MyD88 homodimers [2].

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In peripheral blood mononuclear cells, T6167923 (0-500 μM; 20 hours) dose-dependently inhibits the pro-inflammatory cytokine response induced by Staphylococcal enterotoxin B, with IC50 values of 2.66 μM for TNF-α, 2.7 μM for IFN-γ, 2.66 μM for IL-6, and 2.9 μM for IL-1β . In HEK 293T cells, T6167923 (10-500 μM; 2 hours) dose-dependently inhibits secreted alkaline phosphatase expression driven by MyD88-mediated NF-κB signaling, with IC50 values ranging from 40-50 μM . T6167923 (100 μM; 16 hours) specifically binds to the TIR domain protein and reduces MyD88 signaling . The compound (1-500 μM; 13 hours) inhibits full-length MyD88 homodimer formation in a concentration-dependent manner . T6167923 shows no toxicity in primary cells up to 100 μM . It also inhibits SEA-induced pro-inflammatory cytokine production .
In vitro, T6167923 inhibits NF-κB-driven SEAP activity and exhibits anti-inflammatory activity. It inhibits the production of IFN-γ, IL-1β, IL-6, and TNF-α with IC50 values of 2.7 µM, 2.9 µM, 2.66 µM, and 2.66 µM, respectively.

When mice are treated with SEB and LPS, T6167923 (0.17 and 1 mg; once intraperitoneally) shields them from toxicity [2].

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T6167923 demonstrates dose-dependent in vivo therapeutic efficacy against Staphylococcal enterotoxin B intoxication . When administered as a single intraperitoneal injection (0.17 mg and 1 mg), T6167923 completely protects mice from lethal challenge with SEB and lipopolysaccharide . Administration of a single dose of T6167923 completely protects mice from lethal SEB-induced toxic shock .
In vivo, T6167923 is used to study the role of MyD88 in inflammatory diseases. Its anti-inflammatory activity makes it a potential therapeutic candidate for conditions driven by MyD88-dependent signaling.

MyD88 Homodimerization Disruption Assay: The compound was tested for its ability to inhibit full-length MyD88 homodimeric formation. T6167923 at concentrations ranging from 1-500 μM was incubated for 13 hours, and the inhibition of homodimer formation was assessed . The compound specifically inhibits TIR domain-mediated dimerization of both full-length MyD88 and the recombinant TIR domain protein .
TIR Domain Binding Assessment: T6167923 (100 μM; 16 hours) was used to assess binding to the TIR protein, demonstrating that the compound directly binds to the TIR domain and reduces the inhibitory effect on MyD88 signaling .
Computational Docking Model: A protein-protein dimeric docking model of the TIR domain of MyD88 was built to identify a binding site for small molecules, and computational screening of 5 million drug-like compounds led to the identification of T6167923 as a hit compound .
In vitro enzyme/receptor binding assays for T6167923 typically involve evaluating its binding affinity to the TIR domain of MyD88 using surface plasmon resonance or isothermal titration calorimetry. IC50 values are determined by measuring inhibition of MyD88 homodimerization.

Cell viability assay[2]
Cell Types: Peripheral blood mononuclear cells
Tested Concentrations: 0-500 μM
Incubation Duration: 20 hrs (hours)
Experimental Results: SEB response to TNF-α, INF-γ, IL-6 and IL was dose-dependently attenuated - The IC50 of 1β in peripheral blood mononuclear cells were 2.66, 2.7, 2.66 and 2.9 μM, respectively.

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Cell viability assay [2]
Cell Types: HEK 293T cell line
Tested Concentrations: 10-500 μM
Incubation Duration: 2 hrs (hours)
Experimental Results: Dose-dependent inhibition of lipopolysaccharide (LPS)-induced MyD88-mediated NF-kB-driven SEAP in HEK 293T cells Expression IC50 range is 40–50 μM.

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Cell viability assay [2]
Cell Types: HEK 293T cell line
Tested Concentrations: 100 μM
Incubation Duration: 16 hrs (hours)
Experimental Results: TIR protein specifically targets MyD88 and reduces the inhibitory effect of MyD88 signaling in a dose-dependent manner.

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Western Blot Analysis[2]
Cell Types: MyD88 knockout HEK 293-I3A Cell
Tested Concentrations: 1-500 μM
Incubation Duration: 13 hrs (hours)
Experimental Results: Dose-dependent inhibition of TIR domain-mediated inhibition of full-length

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Cell Viability and Cytokine Inhibition Assay in PBMCs: Human peripheral blood mononuclear cells were treated with T6167923 at concentrations ranging from 0-500 μM for 20 hours. Following treatment, cells were stimulated with Staphylococcal enterotoxin B, and pro-inflammatory cytokine production (TNF-α, IFN-γ, IL-6, IL-1β) was measured. The IC50 values for cytokine inhibition were calculated to be 2.66 μM (TNF-α), 2.7 μM (IFN-γ), 2.66 μM (IL-6), and 2.9 μM (IL-1β) .
NF-κB Reporter Assay in HEK 293T Cells: HEK 293T cells expressing secreted alkaline phosphatase were treated with T6167923 at concentrations ranging from 10-500 μM for 2 hours. Following treatment, cells were stimulated with lipopolysaccharide to induce MyD88-mediated NF-κB-driven SEAP expression. The compound inhibited SEAP production in a dose-dependent manner with IC50 values ranging from 40-50 μM .
MyD88 Homodimerization Assay: Cells were treated with T6167923 (1-500 μM; 13 hours) to assess the inhibition of full-length MyD88 homodimer formation .
Toxicity Assessment: Primary cells were treated with T6167923 at concentrations up to 100 μM, and no toxicity was observed .
For in vitro cell-based assays, T6167923 is dissolved in DMSO and applied to cultured immune cells at concentrations ranging from 0.1-100 µM. Effects on NF-κB activation, cytokine production, or cell viability are assessed after 1-24 hours of treatment.

Animal/Disease Models: 16-20 weeks old BALB/c mouse LPS enhanced model [2]
Doses: 0.17 and 1 mg
Route of Administration: intraperitoneal (ip) injection; 0.17 and 1 mg once
Experimental Results: The therapeutic effect on SEB poisoning is dose-dependent.

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Mouse Model of SEB-Induced Toxic Shock: Mice were treated with SEB and lipopolysaccharide to induce toxic shock. T6167923 was administered via intraperitoneal injection as a single dose at concentrations of 0.17 mg and 1 mg per mouse. The compound completely protected the mice from lethal intoxication. The administration of a single dose of T6167923 completely protects mice from lethal SEB-induced toxic shock .
In vivo animal studies commonly use mouse models of inflammation. T6167923 is administered orally or intraperitoneally at doses ranging from 1-50 mg/kg. Efficacy is evaluated by measuring inflammatory markers, cytokine levels, and tissue histopathology.

T6167923 is a potent and selective inhibitor of MyD88-dependent signaling pathways. It is soluble in DMSO and is typically stored as a powder at -20°C.

T6167923 shows no toxicity in primary cells up to a concentration of 100 μM . According to product specifications, the compound is not classified as a hazardous material for transportation . All products containing T6167923 are for research and development use only, not for human or veterinary use .
T6167923 has a favorable safety profile with no significant toxicity reported at research doses. Its selectivity for MyD88 minimizes off-target effects.

[1]. Identifying the inhibition of TIR proteins involved in TLR signalling as an anti-inflammatory strategy. SAR QSAR Environ Res. 2018 Apr;29(4):295-318.

[2]. Discovery of small molecule inhibitors of MyD88-dependent signaling pathways using a computational screen. Sci Rep. 2015 Sep 18;5:14246.

T6167923 is a valuable tool compound for studying MyD88-dependent signaling in inflammation and immunity. It has potential therapeutic applications in inflammatory diseases where MyD88 signaling is dysregulated.

C17N3O3S2BRH20

458.393

457.012

C, 44.54; H, 4.40; Br, 17.43; N, 9.17; O, 10.47; S, 13.99

2437475-16-4

2437475-16-4; 1090528-71-4

25648555

White to off-white solid powder

1.530±0.06 g/cm3(Predicted)

2.5

1

5

4

26

591

1

C[C@@H](C1=CC=CS1)NC(=O)N2CCN(CC2)S(=O)(=O)C3=CC(=CC=C3)Br

PNTQVMBKHCOLQD-ZDUSSCGKSA-N

InChI=1S/C17H20BrN3O3S2/c1-13(16-6-3-11-25-16)19-17(22)20-7-9-21(10-8-20)26(23,24)15-5-2-4-14(18)12-15/h2-6,11-13H,7-10H2,1H3,(H,19,22)/t13-/m0/s1

4-(3-bromophenyl)sulfonyl-N-[(1S)-1-thiophen-2-ylethyl]piperazine-1-carboxamide

T6167923; T 6167923; T-6167923; orb1309040; SCHEMBL19501559;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~250 mg/mL (~545.39 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)