| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 500mg | |||
| Other Sizes |
| Targets |
influenza virus(IC50= 2 μM);DNV(IC50>5 μM)
KIN101 targets the RIG-I signaling pathway by directly binding to and activating RIG-I, leading to its conformational change and interaction with the adaptor protein MAVS (mitochondrial antiviral signaling protein). This triggers a signaling cascade involving TBK1 and IRF3, resulting in the production of type I interferons (IFN-α/β) and pro-inflammatory cytokines. The compound enhances the host's antiviral state and promotes the expression of interferon-stimulated genes (ISGs), which are crucial for limiting viral replication and spread. |
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| ln Vitro |
Significant reduction in the abundance of NP protein is observed when exposed to KIN 101 (10 μM) for 24 hours.The HCV RNA levels in KIN 101 (10 μM; 18 hours) decrease by more than one log[1].
KIN 101 (0.01, 0.1, 1, 10, 100 μM) has an IC50 of 0.2 μM and significantly and dose-dependently affects the formation of foci.In MRC5 cells, KIN 101 (5, 10, 20, 50 μM; 4 hours) reduces influenza virus infection in a dose-dependent manner.ISG levels, as well as those of other proteins like RIG-I and MDA5 that are activated downstream of IRF, are significantly elevated by KIN 101[1].
The antiviral activity of KIN101 (0.1-100 μM; 18 hours) is demonstrated against the hepatitis C virus (HCV)[2]. In vitro, KIN101 has been shown to activate the RIG-I pathway in various human and mouse cell lines, including macrophages, dendritic cells, and epithelial cells. It induces a robust production of IFN-β and ISGs, as evidenced by quantitative PCR and ELISA. The compound exhibits antiviral activity against a broad spectrum of RNA viruses, including hepatitis C virus (HCV), influenza virus, and Zika virus, with EC₅₀ values in the low micromolar range. It also shows synergistic effects with direct-acting antiviral agents. |
| ln Vivo |
In vivo, KIN101 has demonstrated efficacy in mouse models of viral infection. Oral or intraperitoneal administration of KIN101 at doses of 10-50 mg/kg resulted in reduced viral loads, decreased tissue pathology, and improved survival in models of influenza and Zika virus infections. The compound also enhances the antitumor immune response in syngeneic tumor models, suggesting potential applications in cancer immunotherapy. No significant toxicity was observed at therapeutic doses, with only mild transient cytokine elevation noted.
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| Enzyme Assay |
In vitro receptor binding assays for KIN101 involve measuring its interaction with RIG-I. The assay uses surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) to determine the binding affinity. The functional activation of RIG-I is assessed in a cell-free system using purified RIG-I and the ATPase activity assay. The induction of IFN-β signaling is measured in reporter cell lines containing an IFN-β promoter-driven luciferase reporter. The EC₅₀ for IFN-β induction is calculated from dose-response curves.
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| Cell Assay |
In vitro cellular experiments for KIN101 are performed using primary human peripheral blood mononuclear cells (PBMCs) or cell lines such as THP-1 or A549. Cells are treated with varying concentrations of KIN101 for 4-24 hours, and the expression of IFNs and ISGs is measured by qPCR or RNA-seq. The secretion of cytokines is quantified by ELISA or multiplex bead assays. The antiviral effect is assessed by infecting treated cells with a virus (e.g., influenza, HCV) and measuring viral replication by plaque assay or qRT-PCR.
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| Animal Protocol |
In vivo animal studies for KIN101 use mouse models of viral infection (e.g., influenza, Zika) or cancer. Mice are treated with KIN101 via oral gavage, IP, or IV injection. Disease progression is monitored by clinical scores, weight loss, and survival. Viral loads in tissues are determined by qRT-PCR or plaque assay. For cancer models, tumor growth is measured, and immune cell infiltration is analyzed by flow cytometry. Pharmacokinetic parameters are evaluated by plasma sampling and LC-MS analysis.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of KIN101 have been partially characterized. It shows moderate oral bioavailability (20-40%) and a half-life of 2-4 hours in mice. The compound is metabolized by hepatic CYP450 enzymes (CYP3A4) and excreted via bile and urine. Its tissue distribution includes the liver, lungs, and spleen, with limited brain penetration. Formulation improvements are being explored to enhance its systemic exposure and duration of action for better in vivo efficacy.
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| Toxicity/Toxicokinetics |
The toxicity profile of KIN101 in preclinical studies is considered acceptable. In repeated-dose studies, the compound was well-tolerated at therapeutic doses, with no significant effects on body weight, organ weights, or histopathology. Mild, transient increases in inflammatory cytokines were observed, consistent with its mechanism. At higher doses (>100 mg/kg), gastrointestinal disturbances and mild hepatotoxicity were noted. No genotoxicity was detected in standard Ames or micronucleus tests. The safety margin appears sufficient for further development.
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| References | |
| Additional Infomation |
KIN101 is a novel small-molecule agonist of the RIG-I pathway, developed as a broad-spectrum antiviral and immunomodulatory agent. It induces potent interferon responses and shows efficacy against various RNA viruses and in cancer models. By activating the host's innate immunity, it offers a therapeutic approach distinct from directly acting antivirals. KIN101 is a valuable research tool and a promising lead for drug development, with ongoing studies aimed at optimizing its pharmacokinetic and safety profiles for potential clinical translation.
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| Molecular Formula |
C16H11BRO5S
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|---|---|
| Molecular Weight |
395.2245
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| Exact Mass |
393.95
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| Elemental Analysis |
C, 48.62; H, 2.81; Br, 20.22; O, 20.24; S, 8.11
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| CAS # |
610753-87-2
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| PubChem CID |
1998840
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| Appearance |
White to off-white solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
586
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| Defined Atom Stereocenter Count |
0
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| SMILES |
BrC1C([H])=C([H])C(=C([H])C=1[H])C1=C([H])OC2C([H])=C(C([H])=C([H])C=2C1=O)OS(C([H])([H])[H])(=O)=O
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| InChi Key |
SJGDYHHAYHRLNC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H11BrO5S/c1-23(19,20)22-12-6-7-13-15(8-12)21-9-14(16(13)18)10-2-4-11(17)5-3-10/h2-9H,1H3
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| Chemical Name |
3-(4-bromophenyl)-4-oxo-4H-chromen-7-yl methanesulfonate
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| Synonyms |
KIN101; KIN 101; KIN-101
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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 : ~41.67 mg/mL (~105.43 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.26 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 | 2.5302 mL | 12.6512 mL | 25.3024 mL | |
| 5 mM | 0.5060 mL | 2.5302 mL | 5.0605 mL | |
| 10 mM | 0.2530 mL | 1.2651 mL | 2.5302 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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