STING agonist-3, compound 3, is a selective and non-nucleotide small-molecule STING agonist, which has durable anti-tumor effect and tremendous potential to improve treatment of cancer. STING agonist-3 induces activation of STING and secretion of IFN-β with ECapp50 values of 130 nM, 186 nM in human PBMCs and Mouse PBMCs.
Physicochemical Properties
| Molecular Formula | C37H42N12O6 |
| Molecular Weight | 750.8062 |
| Exact Mass | 750.335 |
| CAS # | 2138299-29-1 |
| Related CAS # | STING agonist-3 trihydrochloride |
| PubChem CID | 131986567 |
| Appearance | White to off-white solid powder |
| LogP | 1.6 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 16 |
| Heavy Atom Count | 55 |
| Complexity | 1390 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O(C([H])([H])C([H])([H])C([H])([H])O[H])C1=C([H])C(C(N([H])[H])=O)=C([H])C2=C1N(C(N([H])C(C1=C([H])C(C([H])([H])[H])=NN1C([H])([H])C([H])([H])[H])=O)=N2)C([H])([H])/C(/[H])=C(\[H])/C([H])([H])N1C(N([H])C(C2=C([H])C(C([H])([H])[H])=NN2C([H])([H])C([H])([H])[H])=O)=NC2C([H])=C(C(N([H])[H])=O)C([H])=C([H])C1=2 |
| InChi Key | VHCDRDBBENBVEK-BQYQJAHWSA-N |
| InChi Code | InChI=1S/C37H42N12O6/c1-5-48-28(16-21(3)44-48)34(53)42-36-40-25-18-23(32(38)51)10-11-27(25)46(36)12-7-8-13-47-31-26(19-24(33(39)52)20-30(31)55-15-9-14-50)41-37(47)43-35(54)29-17-22(4)45-49(29)6-2/h7-8,10-11,16-20,50H,5-6,9,12-15H2,1-4H3,(H2,38,51)(H2,39,52)(H,40,42,53)(H,41,43,54)/b8-7+ |
| Chemical Name | 1-[(E)-4-[5-carbamoyl-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]benzimidazol-1-yl]but-2-enyl]-2-[(2-ethyl-5-methylpyrazole-3-carbonyl)amino]-7-(3-hydroxypropoxy)benzimidazole-5-carboxamide |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | According to research using co-transfection of human embryonic kidney (HEK293T) cells expressing STING and a promoter activated by an interferon response element, STING agonist-3 has a pEC50 value of 7.5 when it comes to activating STING in cells [1]. propelled by luciferase from fireflies. In the FRET assay, STING agonist-3 showed a pIC50 value of 9.5. The purpose of this competition binding assay is to ascertain whether a molecule binds to the human STING C-termination domain (CTD) [1]. |
| References |
[1]. Heterocyclic amides useful as protein modulators.patent WO2017175147A1. [2]. Design of amidobenzimidazole STING receptor agonists with systemic activity [published correction appears in Nature. 2019 Jun;570(7761):E53. doi: 10.1038/s41586-019-1265-5]. Nature. 2018;564(7736):439-443. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~41.67 mg/mL (~55.50 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.77 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 (2.77 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (2.77 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 | 1.3319 mL | 6.6595 mL | 13.3189 mL | |
| 5 mM | 0.2664 mL | 1.3319 mL | 2.6638 mL | |
| 10 mM | 0.1332 mL | 0.6659 mL | 1.3319 mL |