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| Targets |
LIQ1 specifically targets pyruvate kinase M2 (PKM2), a rate-limiting glycolytic enzyme that also regulates immune-related gene expression. The compound binds to the polyarginine pocket of PKM2, where its protonated carboxyl group forms ionic interactions and hydrogen bonds with the Arg43 residue. Mutation of PKM2 Arg43 to alanine significantly reduces LIQ1's binding affinity (Kd) and inhibitory efficacy (IC50), confirming Arg43 as a critical residue. By binding to this allosteric site, LIQ1 prevents PKM2 nuclear translocation and blocks its interaction with HIF-1alpha.
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| ln Vitro |
LIQ1 (100 μM; 2 h) significantly enhanced the thermal stability of PKM2 in the temperature range of 40-52 °C, increasing its melting temperature (Tm) by 3.4 °C[1]. Compared with wild-type PKM2 (IC50 = 0.98 μM; Kd = 3.2 μM), LIQ1 significantly reduced the inhibitory effect on PKM2 R43A (IC50 = 4.10 μM; Kd = 11.1 μM), indicating that R43 is a key residue mediating allosteric inhibition of PKM2[1].
In vitro biochemical assays show that LIQ1 (100 uM; 2 h) enhances PKM2 thermal stability, increasing its melting temperature by 3.4 degC. Compared to wild‑type PKM2 (IC50 = 0.98 uM; Kd = 3.2 uM), LIQ1 shows markedly reduced inhibition on the PKM2 R43A mutant (IC50 = 4.10 uM; Kd = 11.1 uM), confirming that Arg43 is crucial for allosteric inhibition. These cell‑free studies used purified recombinant PKM2 proteins (wild‑type and R43A mutant) to characterize enzymatic inhibition and binding affinity. |
| ln Vivo |
LIQ1 (1, 2, and 5 mg/kg; intraperitoneal injection; administered 0, 12, 24, and 36 hours after LPS injection) significantly improved the anaphylaxis rate of LPS-induced endotoxin and reduced pathogen and organ damage [1]. LIQ1 (20 mg/kg; intraperitoneal injection; single injection; or once daily for 14 days) showed negligible acute toxicity and no hepatotoxicity or nephrotoxicity in mice, supporting its good safety profile [1].
In vivo, LIQ1 (1, 2, 5 mg/kg i.p. at 0,12,24,36 h post-LPS) improved 7‑day survival in LPS‑induced endotoxemia mice from 40% (1 mg/kg) to 80% (5 mg/kg). It dose‑dependently reduced serum IL‑1beta, mitigated LPS‑induced injuries including microvilli loss, villus atrophy, and pathological lesions in lung and heart tissues at 5 mg/kg. LIQ1 also prevented PKM2 nuclear translocation and PKM2‑HIF-1alpha complex formation in small intestine, lung, and heart. |
| Enzyme Assay |
The non‑cellular binding assay for LIQ1 uses purified recombinant wild‑type PKM2 and PKM2 R43A mutant proteins. Surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) quantifies the dissociation constant (Kd). IC50 values are determined via enzymatic activity assays in the presence of varying compound concentrations. Thermal stability is assessed by incubating PKM2 with LIQ1 (100 uM for 2 h) and measuring the melting temperature using differential scanning fluorimetry. These cell‑free systems validate that the Arg43 residue is critical for binding.
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| Cell Assay |
In vitro cell‑based experiments assess PKM2 cellular localization and its interaction with HIF-1alpha. Cells are treated with LIQ1 and stimulated with LPS. Immunofluorescence visualizes PKM2 nuclear translocation, while co‑immunoprecipitation confirms disruption of PKM2‑HIF-1alpha binding. Downstream IL‑1beta levels in culture supernatants are measured by ELISA. For thermal stability in cell lysates, cells are treated with LIQ1 (100 uM, 2 h) and analyzed by CETSA (cellular thermal shift assay). Cell viability is assessed by CCK‑8 or MTT to confirm no cytotoxicity.
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| Animal Protocol |
Animal/Disease Models: Male BALB/c mice (6-8 weeks old) intraperitoneally injected with LPS (13 mg/kg)[1]
Doses: 1, 2, 5 mg/kg Route of Administration: i.p.; administered at 0, 12, 24, and 36 h after LPS injection Experimental Results: Increased the 7-day survival rate from 40% (1 mg/kg) to 80% (5 mg/kg). Exhibited a dose-dependent reduction in serum IL-1β levels. Mitigated the injuries induced by LPS, such as microvilli loss, villus atrophy, deformation, and necrosis. Alleviated the LPS-induced pathological lesions in the lung and heart tissues at the dose of 5 mg/kg. Suppressed LPS-induced ATP accumulation. Significantly inhibited the nuclear translocation of PKM2 in the small intestine, lung, and heart tissues. Prevented PKM2-HIF-1α complex formation, ultimately leading to reduced IL-1β transcription in mice. Animal/Disease Models: Male BALB/c mice (6-8 weeks old)[1] Doses: 20 mg/kg Route of Administration: i.p.; single dose Experimental Results: Showed no significant decrease in body weight over 14 days. Revealed no changes in motor activity, grooming and rubbing behaviors. Animal/Disease Models: Male BALB/c mice (6-8 weeks old)[1] Doses: 20 mg/kg Route of Administration: i.p.; daily for 14 days Experimental Results: Revealed a significant increase in alkaline phosphatase (ALP) levels. Showed no statistically significant changes in other liver enzymes, including AST, ALT, GGT, total protein (TP), albumin (ALB), and globulin (GLO). Showed no significant effects on kidney function parameters, including urea, creatinine (CREA), uric acid (UA), and estimated glomerular filtration rate (eGFR). In vivo animal studies use male BALB/c mice (6‑8 weeks old). LPS‑induced endotoxemia is established by i.p. injection of 13 mg/kg LPS. LIQ1 (1, 2, or 5 mg/kg) is administered i.p. at 0, 12, 24, and 36 hours after LPS. Survival is monitored for 7 days. Serum and tissue samples (small intestine, lung, heart) are collected for IL‑1beta ELISA, histopathological analysis (H&E staining), and assessment of PKM2 nuclear translocation and PKM2‑HIF-1alpha complex formation by immunohistochemistry or immunoblotting. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic parameters (half‑life, Cmax, AUC, oral bioavailability, clearance) for LIQ1 have not been disclosed in the literature. Based on its MW 284.27 and estimated logP ~2.5‑3.0, the compound is expected to have moderate lipophilicity and membrane permeability. LIQ1 is typically administered intraperitoneally in animal studies. Storage recommendations: powder at -20degC for up to 3 years; in solvent at -80degC for up to 1 year. The compound is stable at ambient temperature for several days during shipping.
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| Toxicity/Toxicokinetics |
Toxicity assessments in male BALB/c mice show that LIQ1 (20 mg/kg, single i.p. injection or daily for 14 days) exhibits negligible acute toxicity with no significant body weight loss or changes in motor activity, grooming, or rubbing behaviors. However, daily administration at 20 mg/kg for 14 days caused a significant increase in alkaline phosphatase (ALP) levels, indicating a potential mild hepatotoxic effect. No nephrotoxicity was observed. Comprehensive toxicological studies beyond these observations have not been published. Standard safety precautions should be followed.
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| References | |
| Additional Infomation |
LIQ1 is a research‑grade compound that has not entered clinical trials and is not approved for therapeutic use by any regulatory authority (FDA, EMA, PMDA). It was discovered and reported by Wang et al. in Bioorganic Chemistry (2025, DOI: 10.1016/j.bioorg.2025.109212). The mechanism of action involves allosteric inhibition of PKM2 by targeting Arg43 within the polyarginine pocket, preventing PKM2 nuclear translocation and disrupting PKM2‑HIF-1alpha complex formation, thereby suppressing IL‑1beta transcription. LIQ1 is intended exclusively for preclinical research applications focusing on inflammation, endotoxemia, and PKM2 biology.
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| Molecular Formula |
C16H12O5
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| Molecular Weight |
284.26
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| CAS # |
2606032-80-6
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| Appearance |
Typically exists as solids at room temperature
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5179 mL | 17.5895 mL | 35.1791 mL | |
| 5 mM | 0.7036 mL | 3.5179 mL | 7.0358 mL | |
| 10 mM | 0.3518 mL | 1.7590 mL | 3.5179 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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