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| Targets |
SM-276001 selectively targets Toll-like receptor 7 (TLR7), a pattern recognition receptor involved in innate immunity. TLR7 recognizes single-stranded RNA and activates signaling pathways leading to interferon and cytokine production. By agonizing TLR7, SM-276001 activates NF-κB in a dose-dependent manner via human TLR7. This activation leads to the production of type I interferons (IFN-α/β) and other pro-inflammatory cytokines, which promote antitumor immune responses and immunostimulation. The compound shows selectivity for TLR7 over other TLRs.
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| ln Vitro |
SM-276001 via human TLR7 activates NF-κB in a dose-dependent manner at 1 nM–10 μM[2].
In vitro studies demonstrate that SM-276001 (1 nM-10 μM) dose-dependently activates NF-κB through human TLR7. As an interferon inducer, the compound promotes the production of type I interferons and other cytokines involved in antitumor immunity. The compound's immunostimulatory activity is mediated through TLR7-dependent signaling pathways. In cellular assays, SM-276001 activates downstream signaling cascades including the MyD88-dependent pathway, leading to NF-κB activation and interferon regulatory factor (IRF) activation. The compound demonstrates potent and selective TLR7 agonism without significant activity at other TLRs. |
| ln Vivo |
When given orally to mice at a dose of 0.1 mg/kg, SM-276001 has strong IFN-inducing activity[1]. When SM-276001 is taken orally, it induces an environment of inflammatory cytokines and chemokines and activates a variety of immune effector cells, such as T and B lymphocytes, NK, and NKT cells[2]. In the Renca renal cell cancer and CT26 colorectal models, SM-276001 (3 mg/kg PO biweekly) dramatically reduces tumor growth[2]. In Balb/c and C57BL/6J mice, -276001 (orally; 0.1, 1 or 10 mg/kg) activates a variety of spleen-resident immune effector cells. The MEC of 30 nM is not reached by the plasma concentration of SM-276001 when given at doses of 1 mg/kg or higher[2].
In vivo studies show that SM-276001 significantly reduces tumor burden in mice bearing Renca or CT26 tumors. Oral administration of SM-276001 induces antitumor immune responses in these models. The compound is orally active and induces interferon production in vivo. As an immunomodulatory agent, SM-276001 promotes antitumor immunity through TLR7 activation and subsequent interferon and cytokine production. The compound's efficacy in preclinical models supports its potential for cancer immunotherapy research. Intratracheal administration also induces antitumor immune responses. |
| Enzyme Assay |
The in vitro TLR7 activation assay for SM-276001 involves using HEK293 cells expressing human TLR7 and an NF-κB-driven reporter gene (e.g., luciferase). Cells are treated with varying concentrations of SM-276001 (1 nM-10 μM) for 6-24 hours. Luciferase activity is measured to quantify NF-κB activation. For cytokine production assays, human peripheral blood mononuclear cells (PBMCs) or dendritic cells are treated with the compound and IFN-α, TNF-α, and IL-6 levels are measured by ELISA or multiplex assays. Selectivity is confirmed by testing against other TLR agonists. IC50/EC50 values are determined from dose-response curves using non-linear regression analysis.
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| Cell Assay |
In vitro cellular assays for SM-276001 typically use human TLR7-expressing HEK293 cells or primary immune cells (PBMCs, dendritic cells). Cells are cultured in appropriate media and treated with the compound at concentrations of 0.1-100 μM for 6-48 hours. NF-κB activation is measured using reporter gene assays or by Western blot analysis of phosphorylated downstream targets. Cytokine production (IFN-α, TNF-α, IL-6, IL-12) is measured by ELISA or Luminex assays. Cell viability is assessed using MTT or CCK-8 assays. Dendritic cell maturation is evaluated by flow cytometry analysis of surface markers (CD80, CD86, MHC-II).
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| Animal Protocol |
Animal/Disease Models: C57BL/6 and B6C3F1 mice bearing Renca or CT26 tumors[2]
Doses: 3 mg/kg Route of Administration: Oral administration twice weekly for 25 days Experimental Results: Dramatically decreased disease burden in mice bearing either Renca or CT26 tumors. In vivo animal studies for SM-276001 involve mouse models of cancer including Renca (renal carcinoma) and CT26 (colon carcinoma) tumor models. Mice bearing established tumors are treated with the compound via oral gavage (1-50 mg/kg) or intratracheal administration daily or on a scheduled basis for 2-4 weeks. Tumor volume is measured regularly and tumor weight is determined at necropsy. Tumor-infiltrating lymphocytes are analyzed by flow cytometry. Cytokine levels in plasma and tumor tissues are measured by ELISA. Survival analysis is performed. Immune cell populations in spleen and lymph nodes are characterized. Histological analysis of tumors is performed to assess immune infiltration. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of SM-276001 indicate good oral bioavailability. The compound has a molecular weight of 327.38 and molecular formula of C16H21N7O. It is soluble in DMSO and other organic solvents. The compound should be stored at -20°C for long-term preservation and at -80°C in solvent. After oral administration, the compound reaches systemic circulation and distributes to tissues. The interferon-inducing activity is observed within hours of administration. Further studies on plasma half-life, clearance, volume of distribution, and protein binding are needed to fully characterize its PK profile.
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| Toxicity/Toxicokinetics |
Toxicological data for SM-276001 is not extensively reported. As an immunostimulatory TLR7 agonist, the compound may cause cytokine-related side effects including fever, flu-like symptoms, and immune-related adverse events. The compound is for research use only and not for human therapeutic applications. Standard safety precautions should be followed when handling. For detailed toxicity information, including acute toxicity, genotoxicity, and organ-specific toxicity, specialized toxicological studies would need to be performed in appropriate animal models.
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| References |
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| Additional Infomation |
SM-276001 is a research-grade compound with a purity of ≥98%. Its CAS number is 473930-22-2 and molecular formula is C16H21N7O. The molecular weight is 327.38. The compound is a potent and selective TLR7 agonist and orally active interferon inducer. It induces antitumor immune responses and is being investigated for cancer immunotherapy research. The mechanism of action involves TLR7 activation leading to NF-κB activation, interferon production, and immune stimulation. This compound has not advanced to clinical trials and is not FDA-approved. It is strictly for research purposes only.
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| Molecular Formula |
C16H21N7O
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| Molecular Weight |
327.384241819382
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| Exact Mass |
327.18
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| CAS # |
473930-22-2
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| Related CAS # |
473930-22-2;473930-50-6 (sulfate);
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| PubChem CID |
10359083
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
1.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
24
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| Complexity |
435
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1NC2C(N)=NC(NCCCC)=NC=2N1CC1C=NC(C)=CC=1
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| InChi Key |
UEIOLEMXCBOQAX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H21N7O/c1-3-4-7-18-15-21-13(17)12-14(22-15)23(16(24)20-12)9-11-6-5-10(2)19-8-11/h5-6,8H,3-4,7,9H2,1-2H3,(H,20,24)(H3,17,18,21,22)
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| Chemical Name |
6-amino-2-(butylamino)-9-((6-methylpyridin-3-yl)methyl)-9H-purin-8-ol
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| Synonyms |
SM276001 SM 276001 SM-276001.
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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 (~381.82 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.35 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.35 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0546 mL | 15.2728 mL | 30.5455 mL | |
| 5 mM | 0.6109 mL | 3.0546 mL | 6.1091 mL | |
| 10 mM | 0.3055 mL | 1.5273 mL | 3.0546 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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