| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
Toll-like receptor 7 (TLR7) - potent and selective agonist (EC50 = 7.2 nM for human; 4.6 nM for mouse).
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| ln Vitro |
An NF-κB-driven reporter experiment is carried out in HEK293 cells that have been modified to express either hTLR7, TLR8, or TLR9 in order to evaluate the selectivity of DSR-6434 toward TLR7. In this experiment, NF-κB is activated upon successful binding of DSR-6434 to the particular receptor. Only HEK293 cells expressing hTLR7 can be stimulated by DSR-6434 to activate reporter genes; HEK293 cells expressing hTLR8 or hTLR9, which are physically identical, cannot be stimulated[2].
In vitro studies demonstrate that DSR-6434 is a potent and selective TLR7 agonist, activating several immune effector cells. The compound has TLR7 EC50 values of 7.2 nM for human and 4.6 nM for mouse TLR7. TLR7 is a pattern recognition receptor that recognizes single-stranded RNA and activates innate immune responses, leading to the production of type I interferons and pro-inflammatory cytokines. By activating TLR7, DSR-6434 stimulates dendritic cells, macrophages, and other immune cells, promoting anti-tumor immune responses. The compound has a strong antitumor effect. |
| ln Vivo |
Compound 20 (0.1–1 mg/kg; intravenous injection; every two weeks; B6C3F1 mice) administered intraperitoneally for four weeks strongly suppresses lung metastasis, with 78% suppression at 0.1 mg/kg dose (no tumor metastasis in the 1 mg/kg group)[1].
In vivo studies have demonstrated that DSR-6434 suppresses metastasis and enhances the efficacy of radiation therapy in a model of colorectal carcinoma. The compound (0.1 mg/kg) reduces tumor volume and increases survival, as well as potentiates the antitumor effects of ionizing radiation, in a CT26 murine colon cancer model. By activating TLR7 and stimulating innate immune responses, DSR-6434 promotes anti-tumor immunity and enhances the effectiveness of other cancer therapies. The compound's potent immune-activating and tumor-suppressive properties make it a valuable research tool for cancer immunotherapy. |
| Enzyme Assay |
TLR7 activation assays are performed using TLR7-expressing reporter cell lines or primary immune cells. Cells are treated with DSR-6434 at various concentrations, and TLR7 activation is assessed by measuring NF-κB activation (using luciferase reporter assays) or by measuring cytokine production (IFN-α, TNF-α, IL-12) by ELISA. EC50 values are calculated from dose-response curves. Selectivity over other TLRs (TLR3, TLR8, TLR9) is assessed using similar assay formats to confirm the compound's specificity for TLR7.
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| Cell Assay |
Cellular assays for DSR-6434 typically involve culturing immune cells such as dendritic cells, macrophages, or peripheral blood mononuclear cells (PBMCs) and treating them with the compound at various concentrations. TLR7 activation is assessed by measuring cytokine production (IFN-α, TNF-α, IL-12, IL-6) by ELISA or multiplex assays. Immune cell activation and maturation are assessed by flow cytometry for cell surface markers (CD80, CD86, MHC class II, CD40). The compound's ability to stimulate anti-tumor immune responses is assessed in co-culture assays with cancer cells. Cytotoxicity against mammalian cells is assessed in parallel to evaluate selectivity.
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| Animal Protocol |
Animal/Disease Models: B6C3F1 mice injected with HM-1 ovarian cancer cells[1]
Doses: 0.1 mg/kg, 1 mg/kg Route of Administration: intravenous (iv) injection; biweekly; for 4 weeks Experimental Results: Suppressed the Lung metastasis Dramatically, 78% inhibition was seen at 0.1 mg/kg dosing (with no tumor metastasis at the 1 mg/kg group). In vivo efficacy of DSR-6434 is evaluated in mouse models of cancer, such as the CT26 murine colon cancer model. Tumor-bearing mice are treated with DSR-6434 via oral or intraperitoneal administration, and tumor volume is monitored over time. The compound's ability to suppress metastasis and enhance the efficacy of radiation therapy is assessed in combination studies. Tumor immune cell infiltration is assessed by flow cytometry for immune cell populations. Cytokine levels in serum and tumor tissues are measured by ELISA. Endpoints include tumor growth inhibition, metastasis reduction, survival, and immune cell infiltration and activation. Pharmacokinetic studies are conducted to determine the compound's bioavailability and tissue distribution. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of DSR-6434 have been characterized to support its use as a research tool. The compound has a molecular weight of 400.48 and the molecular formula C19H28N8O2. DSR-6434 indicated an optimal balance between agonistic potency and high water solubility. Key PK parameters including half-life, clearance, volume of distribution, and oral bioavailability are determined using LC-MS/MS analysis of plasma and tissue samples following administration. The compound's ability to reach tumors and lymphoid organs is important for its efficacy in cancer immunotherapy models. The compound should be stored as a powder at -20°C.
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| Toxicity/Toxicokinetics |
Toxicological evaluation of DSR-6434 is typically conducted in parallel with efficacy studies in animal models. Standard toxicology assessments include in vitro cytotoxicity assays against a panel of mammalian cell lines to determine the compound's selectivity index. In vivo toxicity studies in rodents include acute and repeated-dose toxicity testing, observation of clinical signs and body weight changes, and histopathological examination of major organs including the spleen and lymph nodes. As a TLR7 agonist that stimulates innate immune responses, potential effects on systemic inflammation, autoimmunity, and cytokine release syndrome are carefully monitored.
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| References |
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| Additional Infomation |
DSR-6434 is a research tool compound used for studying the role of Toll-like receptor 7 in cancer immunotherapy, innate immune signaling, and TLR-targeted drug discovery. The compound is not approved for clinical use and is intended for laboratory research purposes only. Its mechanism of action involves potent and selective agonism of TLR7, which activates innate immune responses, promotes anti-tumor immunity, and enhances the efficacy of other cancer therapies. DSR-6434 suppresses metastasis and enhances the efficacy of radiation therapy in models of colorectal carcinoma. This compound is valuable for validating TLR7 as a therapeutic target for cancer immunotherapy and for investigating the role of innate immune signaling in anti-tumor responses.
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| Molecular Formula |
C19H28N8O2
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| Molecular Weight |
400.487
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| Exact Mass |
400.233
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| Elemental Analysis |
C, 56.98; H, 7.05; N, 27.98; O, 7.99
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| CAS # |
1059070-10-8
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| PubChem CID |
25071151
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.635
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| LogP |
0.23
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
29
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| Complexity |
522
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1NC2C(N)=NC(NCCCC)=NC=2N1CC1C=NC(=CC=1)OCCN(C)C
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| InChi Key |
SSZHESNDOMBSRV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H28N8O2/c1-4-5-8-21-18-24-16(20)15-17(25-18)27(19(28)23-15)12-13-6-7-14(22-11-13)29-10-9-26(2)3/h6-7,11H,4-5,8-10,12H2,1-3H3,(H,23,28)(H3,20,21,24,25)
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| Chemical Name |
6-Amino-2-(butylamino)-9-[[6-[2-(dimethylamino)ethoxy]-3-pyridinyl]methyl]-7,9-dihydro-8H-purin-8-one
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| Synonyms |
DSR6434 DSR 6434 DSR-6434
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~312.13 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.50 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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. Solubility in Formulation 2: ≥ 1 mg/mL (2.50 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 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4969 mL | 12.4847 mL | 24.9694 mL | |
| 5 mM | 0.4994 mL | 2.4969 mL | 4.9939 mL | |
| 10 mM | 0.2497 mL | 1.2485 mL | 2.4969 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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