1. Immunology/Inflammation
  2. STING IFNAR Interleukin Related
  3. SNX281

SNX281 is a selective STING agonist, with IC50 values of 4.1, 4.5, 10.7, and 3.7 μM against human, mouse, rat, and monkey STING, respectively. SNX281 undergoes homodimerization at the STING binding site, triggering a conformational shift of STING from an inactive open state to an active closed state, thereby driving downstream STING-dependent signaling pathways. SNX281 induces type I interferons, IFN-β, TNF-α, IL-6, cytokine release, T cell responses, and long-lasting immune memory. SNX281 exhibits anti-tumor activity and is applicable to research related to colorectal cancer, melanoma, advanced solid tumors, lymphoma, and ovarian cancer.

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SNX281

SNX281 Chemical Structure

CAS No. : 2332803-84-4

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
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Based on 1 publication(s) in Google Scholar

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Description

SNX281 is a selective STING agonist, with IC50 values of 4.1, 4.5, 10.7, and 3.7 μM against human, mouse, rat, and monkey STING, respectively. SNX281 undergoes homodimerization at the STING binding site, triggering a conformational shift of STING from an inactive open state to an active closed state, thereby driving downstream STING-dependent signaling pathways. SNX281 induces type I interferons, IFN-β, TNF-α, IL-6, cytokine release, T cell responses, and long-lasting immune memory. SNX281 exhibits anti-tumor activity and is applicable to research related to colorectal cancer, melanoma, advanced solid tumors, lymphoma, and ovarian cancer[1].

In Vitro

SNX281 (25 µM; 1 h) induces STING translocation, TBK1 phosphorylation, and IRF3 nuclear translocation in HEK293T cells stably expressing human HAQ-mutant STING[1].
SNX281 (10 µM; 0-2 h) rapidly induces the phosphorylation of STING, TBK1 and IRF3 in THP-1 cells[1].
SNX281 (6 h) induces dose-dependent secretion of IFN-β, TNF-α and IL-6 in THP-1 cells[1].
SNX281 induces IRF3 and NF-κB reporter gene activity in a STING-dependent manner in THP1-Dual cells, with an EC50 value of 1.1 µM for human wild-type STING and 1.7 µM for human HAQ mutant STING[1].
SNX281 (6 h) induces dose-dependent IFN-β secretion in J774A.1 mouse macrophage-like cells, with an EC50 of 5.4 µM[1].
SNX281 (6 h) induces dose-dependent IFN-β secretion in peripheral blood mononuclear cells of cynomolgus monkeys, with an EC50 of 2.4 µM[1].
SNX281 induces STING-dependent pathway activation in THP-1 cells and human peripheral blood mononuclear cells (PBMCs), and promotes the production of IFN-β, TNF-α and IL-6[2].

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

ELISA Assay[1]

Cell Line: THP-1 cells
Concentration: /
Incubation Time: 6 hours
Result: Induced dose-dependent secretion of IFN-β with an EC50 of 6.6 µM.
Induced dose-dependent secretion of TNF-α with an EC50 of 7.9 µM.
Induced dose-dependent secretion of IL-6 with an EC50 of 5.5 µM.
Parmacokinetics
Species Dose Route T1/2 AUC0-∞ Vss CL
Mice[1] 5 mg/kg i.v. 2.33 h 16766 ng·h/mL 0.984 L/kg 4.97 mL/min/kg
In Vivo

SNX281 (10-45 mg/kg; intravenous injection; single bolus) induces a rapid, transient, and dose-dependent type I interferon response in healthy C57BL/6 mice[1].
SNX281 (12.5-45 mg/kg; intravenous administration) exhibits dose-dependent antitumor activity in the BALB/c CT26 colorectal cancer model[1].

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

Animal Model: C57BL/6 (male/female)[1]
Dosage: 10 mg/kg; 25 mg/kg; 35 mg/kg; 45 mg/kg
Administration: i.v.; single bolus
Result: Induced dose-dependent elevated plasma IFN-β levels at 3 hours post-dose, with levels highest at 3 hours, reduced at 6 hours, and undetectable by 24 hours across all doses.
Animal Model: BALB/c ( colorectal cancer model via subcutaneous inoculation of CT26.WT cells)[1]
Dosage: 12.5 mg/kg (Days 1/4/7 dosing); 25 mg/kg (Days 1/4/7 dosing); 25 mg/kg (b.i.d. on Day 1); 35 mg/kg (single dose); 45 mg/kg (single dose)
Administration: i.v.; single doses on Days 1, 4, 7; i.v.; two doses 2 hours apart on Day 1; i.v.; single bolus on Day 1
Result: Yielded 0/8 complete responses (CRs) at 12.5 mg/kg (Days 1/4/7).
Yielded 1/8 CRs at 25 mg/kg (Days 1/4/7).
Yielded 3/8 CRs at 25 mg/kg (b.i.d.
on Day 1).
Yielded 8/8 CRs (complete tumor regression in all mice) at 35 mg/kg (single dose).
Yielded 8/8 CRs (complete tumor regression in all mice) at 45 mg/kg (single dose).
Increased circulating CD8+ T cells by ~2-fold at 35 mg/kg or 45 mg/kg single doses compared to vehicle controls.
Caused no significant body weight loss across all treatment groups.
Molecular Weight

389.90

Formula

C20H20ClNO3S

CAS No.
Appearance

Solid

Color

Off-white to light yellow

SMILES

O=C(CN1C2=CC(C(C)(C)C)=CC=C2C(C3=CC=C(C(SC)=C31)Cl)=O)O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

Solvent & Solubility
In Vitro: 

DMSO : 15 mg/mL (38.47 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.5648 mL 12.8238 mL 25.6476 mL
5 mM 0.5130 mL 2.5648 mL 5.1295 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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In Vivo Dissolution Calculator
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Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.5648 mL 12.8238 mL 25.6476 mL 64.1190 mL
5 mM 0.5130 mL 2.5648 mL 5.1295 mL 12.8238 mL
10 mM 0.2565 mL 1.2824 mL 2.5648 mL 6.4119 mL
15 mM 0.1710 mL 0.8549 mL 1.7098 mL 4.2746 mL
20 mM 0.1282 mL 0.6412 mL 1.2824 mL 3.2060 mL
25 mM 0.1026 mL 0.5130 mL 1.0259 mL 2.5648 mL
30 mM 0.0855 mL 0.4275 mL 0.8549 mL 2.1373 mL
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Help & FAQs
  • 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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SNX281
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