Cat. No.: HY-182377

DT-5461

DT-5461 is an IL-1 and TNF-α antagonist. DT-5461 competitively binds lipid A-binding sites on macrophage receptors, blocks LPS (HY-D1056)-initiated signaling, inhibits LPS-induced cytokine release, prevents LPS-induced serum cytokine production in mice, and protects against LPS-induced lethal endotoxemia. DT-5461 can be used for the research of lethal endotoxemia, medullary tubular mammary carcinoma, poorly differentiated colon adenocarcinoma, squamous-cell lung carcinoma, and gelatinous gastric adenocarcinoma.

For research use only. We do not sell to patients.

CAS No.: 123598-19-6
Formula: C₇₃H₁₃₃N₄O₂₂P
Molecular Weight:1449.82

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

DT-5461 Chemical Structure

CAS No.: 123598-19-6

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Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Protocols (3)
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

^[1]

IL-1

All Interleukin Related Isoforms :

All TNF Receptor Isoforms :

In Vitro

DT-5461 (0.1-10 μg/mL; 2 h pre-incubation) acts as an LPS antagonist in human peripheral blood monocytes, significantly inhibiting E. coli LPS-induced IL-1 and TNF-α secretion in a concentration-dependent manner, with maximal suppression observed at 10 μg/mL^[1].
DT-5461 (10 μg/mL; 4 h) stimulates TNF production in IFN-γ-treated nude mouse peritoneal macrophages, and this production is augmented 2-4 times by co-culture with PC-6, QG56, or MX-1 human tumor cells, with MX-1 cells exerting the strongest augmentative effect^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.

In Vivo

DT-5461 (1-100 μg per mouse; i.p.; single dose) dose-dependently prevents LPS-induced lethal endotoxemia in D-galactosamine-sensitized C57BL/6 mice, with a 100% survival rate achieved at a dose of 100 μg per mouse, and inhibits LPS-mediated serum IL-1 and TNF-α production^[1].
DT-5461 (i.v.; 4-6 doses) exhibits an LD₅₀ greater than 68000 ng/kg via bolus intravenous injection and greater than 20000 ng/kg via drip intravenous infusion in naive male Sprague-Dawley rats, with no difference in lethality between administration routes at tested doses^[2].
DT-5461 (i.v.; 4-6 doses) exhibits an LD₅₀ greater than 400 ng/kg via bolus intravenous injection in 2/3 hepatectomized male Sprague-Dawley rats, with enhanced but lower-potency lethality compared to C506 and LPS^[2].
DT-5461 (35 mg/kg; i.v.; single dose) induces persistent splenomegaly, transient increases in blood cell counts and serum IgG, and splenic B-cell and T-cell population changes in naive male Sprague-Dawley rats, with characteristic histopathological alterations^[2].
DT-5461 (1.0-2.5 mg/kg; i.v.; drip infusion; single dose) does not induce DIC-related clinico-pathological changes in 0.4 M lactic acid-pretreated male Sprague-Dawley rats^[2].
DT-5461 (0.64-10 mg/kg; i.v.; daily; 14 days) induces splenomegaly at 0.64 mg/kg or higher, decreased platelet counts and hepatocellular necrosis at 4 mg/kg or higher, and increased serum alanine aminotransferase at 10 mg/kg in male Sprague-Dawley rats^[2].
DT-5461 (4-25 mg/kg; i.v.; daily; 14 days) causes no changes at 4 mg/kg, slight hepatocellular necrosis and reticuloendothelial system activation at 10 mg/kg, and increased serum alanine aminotransferase, extensive hepatocellular necrosis, and reticuloendothelial system activation at 25 mg/kg in male squirrel monkeys^[2].
DT-5461 (200 μg/mouse; i.v.; three times at 5-day intervals) exhibits significant antitumor activity against Meth A fibrosarcoma in BALB/c mice, resulting in a T/C value of 29%^[3].
DT-5461 (200 μg/mouse; i.v.; three times at 5-day intervals) exhibits significant antitumor activity against Meth A fibrosarcoma in BALB/c-nu/nu mice, resulting in a T/C value of 35%^[3].
DT-5461 (200-800 μg/mouse; i.v.; 9 times at 3-day intervals) exhibits dose-dependent, statistically significant antitumor activity against PC-6 oat-cell lung carcinoma in BALB/c-nu/nu mice, with T/C values of 21% at 200 μg/mouse and 8% at 800 μg/mouse, and induces intratumoral TNF activity that correlates with antitumor efficacy^[3].
DT-5461 (200-800 μg/mouse; i.v.; 9 times at 3-day intervals) exhibits dose-dependent, statistically significant antitumor activity against MX-1 medullary tubular mammary carcinoma in BALB/c-nu/nu mice, with T/C values of 30% at 200 μg/mouse and 14% at 800 μg/mouse, and induces high intratumoral TNF activity that correlates with antitumor efficacy^[3].
DT-5461 (200-800 μg/mouse; i.v.; 9 times at 3-day intervals) exhibits statistically significant antitumor activity against Co-4 poorly differentiated colon adenocarcinoma in BALB/c-nu/nu mice, with T/C values of 27% at 200 μg/mouse and 29% at 800 μg/mouse, and induces high intratumoral TNF activity that correlates with antitumor efficacy^[3].
DT-5461 (200-800 μg/mouse; i.v.; 9 times at 3-day intervals) exhibits dose-dependent, statistically significant antitumor activity against QG56 squamous-cell lung carcinoma in BALB/c-nu/nu mice, with T/C values of 54% at 200 μg/mouse and 27% at 800 μg/mouse, and induces intratumoral TNF activity that correlates with antitumor efficacy^[3].
DT-5461 (200-800 μg/mouse; i.v.; 9 times at 3-day intervals) exhibits dose-dependent antitumor activity against SC-6 poorly differentiated gastric adenocarcinoma in BALB/c-nu/nu mice, with a statistically significant T/C value of 32% at 800 μg/mouse, and induces intratumoral TNF activity that correlates with antitumor efficacy^[3].
DT-5461 (200-800 μg/mouse; i.v.; 9 times at 3-day intervals) exhibits weak antitumor activity against St-15 gelatinous gastric adenocarcinoma in BALB/c-nu/nu mice, with T/C values of 72% at 200 μg/mouse and 57% at 800 μg/mouse, and induces low intratumoral TNF activity^[3].

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

Animal Model:

C57BL/6 (female, 7-10 weeks old, specific-pathogen-free, sensitized with E. coli 0127:B8 LPS and D-galactosamine for lethal endotoxemia model)^[1]
Dosage:

1 μg per mouse; 10 μg per mouse; 100 μg per mouse
Administration:

i.p.; single dose
Result:

Inhibited LPS-mediated increases in endogenous serum IL-1 and TNF-α in a dose-dependent manner.
Reduced serum IL-1 and TNF-α levels significantly relative to LPS-only controls at 1 μg per mouse.
Achieved greater reductions in serum IL-1 and TNF-α levels at 10 μg per mouse.
Suppressed serum IL-1 and TNF-α levels most strongly at 100 μg per mouse (P < 0.001 vs.
LPS-only group).
Resulted in 37.5% (3/8) survival rate through day 6 at 1 μg per mouse.
Resulted in 75% (6/8) survival rate through day 6 at 10 μg per mouse.
Resulted in 100% (8/8) survival rate through day 6 at 100 μg per mouse.
Had a 50% protection dose of 2.1 μg per mouse and a 100% protection dose of 25 μg per mouse.

Animal Model:

Sprague-Dawley (male, 8-9 weeks old, 220-260 g)^[2]
Dosage:

35 mg/kg
Administration:

i.v.; single bolus injection
Result:

Induced splenomegaly from day 1, with no full recovery to control levels by day 28.
Caused a marked increase in white blood cell, lymphocyte, and neutrophil counts on days 3-6, returning to baseline by day 28.
Induced serum IgG levels to peak between days 2-6, mirroring white blood cell fluctuations.
Caused splenic nucleated cells to increase from day 3.
Induced B-cells to significantly increase from day 3, and T-cells to increase from day 14.
Caused enlargement of B-cell area lymphatic follicles with large phagocytic cell infiltration and decreased T-cell area lymphocytes from 6 h to day 3.
Triggered lympho-reticular cell proliferation in the red pulp zone from days 1-28.
Induced megakaryopoiesis on days 2-6, and enhanced erythropoiesis on days 4-6.

Animal Model:

Sprague-Dawley (male, 8-9 weeks old, 220-260 g, lactic acid-pretreated)^[2]
Dosage:

1.0 mg/kg; 2.5 mg/kg
Administration:

i.v.; drip infusion; single dose
Result:

Caused no changes in platelet counts, activated partial thromboplastin time, fibrin-fibrinogen degradation products, serum alanine aminotransferase, or urea nitrogen at both 1.0 mg/kg and 2.5 mg/kg.
Showed no hepatocellular necrosis or glomerular fibrin thrombus formation at both doses, unlike C506 and LPS.

Animal Model:

Sprague-Dawley (male, 8-9 weeks old, 220-260 g)^[2]
Dosage:

0.64 mg/kg; 1.6 mg/kg; 4 mg/kg; 10 mg/kg
Administration:

i.v.; bolus injection; daily; 14 days
Result:

Induced splenomegaly at all doses (0.64 mg/kg or more).
Caused decreased platelet counts and single hepatocellular necrosis at 4 mg/kg or more.
Induced increased serum alanine aminotransferase activity at 10 mg/kg.

Animal Model:

Squirrel monkey (male, over 4 years old, 0.7-1 kg)^[2]
Dosage:

4 mg/kg; 10 mg/kg; 25 mg/kg
Administration:

i.v.; bolus injection; daily; 14 days
Result:

Caused no changes at 4 mg/kg.
Induced slight hepatocellular necrosis and moderate activation of the hepatic and splenic reticuloendothelial system at 10 mg/kg.
Caused increased serum alanine aminotransferase activity, extensive hepatocellular necrosis, and extensive activation of the hepatic and splenic reticuloendothelial system at 25 mg/kg.
Showed no effects on organ weights at any dose.

Animal Model:

BALB/c (male, 6-week-old, intradermal inoculation of Meth A fibrosarcoma cells)^[3]
Dosage:

200 μg/mouse
Administration:

i.v.; three times at 5-day intervals
Result:

Produced a statistically significant tumor growth inhibitory effect with a T/C value of 29% relative to control mice.

Animal Model:

BALB/c-nu/nu (nude, male, 6-week-old, intradermal inoculation of Meth A fibrosarcoma cells)^[3]
Dosage:

200 μg/mouse
Administration:

i.v.; three times at 5-day intervals
Result:

Produced a statistically significant tumor growth inhibitory effect with a T/C value of 35% relative to control mice.

Animal Model:

BALB/c-nu/nu (nude, male, 6-week-old, subcutaneous transplantation of PC-6 tumor pieces)^[3]
Dosage:

200 μg/mouse; 800 μg/mouse
Administration:

i.v.; 9 times at 3-day intervals
Result:

Produced a mean tumor weight of 0.65 g, a statistically significant T/C value of 21% relative to control mice at 200 μg/mouse.
Produced a mean tumor weight of 0.24 g, a statistically significant T/C value of 8% relative to control mice at 800 μg/mouse.
Induced intratumoral TNF activity with a single i.v.
dose of 200 μg/mouse.
Induced higher intratumoral TNF activity and serum TNF activity with a single i.v.
dose of 800 μg/mouse.

Animal Model:

BALB/c-nu/nu (nude, male, 6-week-old, subcutaneous transplantation of MX-1 tumor pieces)^[3]
Dosage:

200 μg/mouse; 800 μg/mouse
Administration:

i.v.; 9 times at 3-day intervals
Result:

Produced a mean tumor weight of 1.98 g, a statistically significant T/C value of 30% relative to control mice at 200 μg/mouse.
Produced a mean tumor weight of 0.90 g, a statistically significant T/C value of 14% relative to control mice at 800 μg/mouse.
Induced intratumoral TNF activity with a single i.v.
dose of 200 μg/mouse.
Induced higher intratumoral TNF activity and serum TNF activity with a single i.v.
dose of 800 μg/mouse.
Augmented DT-5461-stimulated macrophage TNF production 4-fold in vitro by MX-1 tumor cells.

Animal Model:

BALB/c-nu/nu (nude, male, 6-week-old, subcutaneous transplantation of Co-4 tumor pieces)^[3]
Dosage:

200 μg/mouse; 800 μg/mouse
Administration:

i.v.; 9 times at 3-day intervals
Result:

Produced a mean tumor weight of 0.49 g, a statistically significant T/C value of 27% relative to control mice at 200 μg/mouse.
Produced a mean tumor weight of 0.51 g, a statistically significant T/C value of 29% relative to control mice at 800 μg/mouse.
Induced intratumoral TNF activity with a single i.v.
dose of 200 μg/mouse.
Induced higher intratumoral TNF activity and serum TNF activity with a single i.v.
dose of 800 μg/mouse.

Animal Model:

BALB/c-nu/nu (nude, male, 6-week-old, subcutaneous transplantation of QG56 tumor pieces)^[3]
Dosage:

200 μg/mouse; 800 μg/mouse
Administration:

i.v.; 9 times at 3-day intervals
Result:

Produced a mean tumor weight of 1.97 g, a statistically significant T/C value of 54% relative to control mice at 200 μg/mouse.
Produced a mean tumor weight of 0.98 g, a statistically significant T/C value of 27% relative to control mice at 800 μg/mouse.
Induced intratumoral TNF activity with a single i.v.
dose of 200 μg/mouse.
Induced higher intratumoral TNF activity and serum TNF activity with a single i.v.
dose of 800 μg/mouse.
Augmented DT-5461-stimulated macrophage TNF production 2-fold in vitro by QG56 tumor cells.

Animal Model:

BALB/c-nu/nu (nude, male, 6-week-old, subcutaneous transplantation of SC-6 tumor pieces)^[3]
Dosage:

200 μg/mouse; 800 μg/mouse
Administration:

i.v.; 9 times at 3-day intervals
Result:

Produced a mean tumor weight of 1.37 g, a T/C value of 44% relative to control mice at 200 μg/mouse.
Produced a mean tumor weight of 1.01 g, a statistically significant T/C value of 32% relative to control mice at 800 μg/mouse.
Induced intratumoral TNF activity with a single i.v.
dose of 200 μg/mouse.
Induced higher intratumoral TNF activity and serum TNF activity with a single i.v.
dose of 800 μg/mouse.

Animal Model:

BALB/c-nu/nu (nude, male, 6-week-old, subcutaneous transplantation of St-15 tumor pieces)^[3]
Dosage:

200 μg/mouse; 800 μg/mouse
Administration:

i.v.; 9 times at 3-day intervals
Result:

Produced a mean tumor weight of 1.00 g, a T/C value of 72% relative to control mice at 200 μg/mouse.
Produced a mean tumor weight of 0.79 g, a T/C value of 57% relative to control mice at 800 μg/mouse.
Induced low intratumoral TNF activity with a single i.v.
dose of 200 μg/mouse.
Induced higher intratumoral TNF activity and serum TNF activity with a single i.v.
dose of 800 μg/mouse.

Chemical Information

CAS No. 123598-19-6
Molecular Weight 1449.82
Formula C₇₃H₁₃₃N₄O₂₂P
SMILES

CCCCCCCCCCCCCC(N[C@@H]1[C@H]([C@@H]([C@H](O[C@H]1OC[C@H]2O[C@@H]([C@@H]([C@H]([C@@H]2O)OC(CNC(CCCCCCCCCCC)=O)=O)NC(CCCCCCCCCCCCC)=O)OC(CC(O)=O)CC(O)=O)CO)OP(O)(O)=O)OC(CNC(CCCCCCCCCCC)=O)=O)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

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

Protocols

All Animals and Diseases Signal Pathway Related

LPS-Induced Endotoxemia/Systemic Inflammation
Lipopolysaccharide (LPS)-induced endotoxemia is a widely used in vivo model of acute systemic inflammation in which LPS, a Gram-negative bacterial endotoxin, activates innate immune signaling primarily through TLR4, leading to rapid and transient induction of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β in circulation and tissues. This cytokine surge is commonly used as a measurable readout of systemic inflammatory activation and immune dysregulation, and is typically assessed within hours after intraperitoneal LPS administration in mouse models of endotoxemia. The model captures key features of systemic inflammatory response syndrome, including cytokine release, immune cell activation, and downstream tissue responses, and has been used to evaluate anti-inflammatory interventions such as cytokine modulation, lipid mediators, and immune cell-targeting therapies.
Research Protocol for Inflammation-related Diseases
The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co
Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.

Purity & Documentation

Handling Instructions (2659 KB)

References

[1]. Sato K, et al. A novel synthetic lipid A analog with low endotoxicity, DT-5461, prevents lethal endotoxemia. Infect Immun. 1995;63(8):2859-2866. [Content Brief]

[2]. Sagara-Ishijima N, et al. Toxic characteristics of the synthetic lipid A derivative DT-5461 in rats and monkeys. Toxicol Sci. 1999;49(2):324-331. [Content Brief]

[3]. Kumazawa E, et al. Antitumor effect of DT-5461, a lipid A derivative, against human tumor xenografts is mediated by intratumoral production of tumor necrosis factor and affected by host immunosuppressive factors in nude mice. Cancer Invest. 1997;15(6):522-530. [Content Brief]

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DT-5461

All Interleukin Related Isoforms

All TNF Receptor Isoforms