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| 5mg |
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| Other Sizes |
| Targets |
AXKO-0046 dihydrochloride selectively and uncompetitively targets lactate dehydrogenase B (LDHB), one of the two isoforms of lactate dehydrogenase. It binds to a potential allosteric site away from the LDHB catalytic active site, targeting the tetramerisation interface of the two dimers, which is critical for enzymatic activity. This compound does not significantly inhibit LDHA or other histone methyltransferases, demonstrating high selectivity for LDHB.
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| ln Vitro |
XKO-0046 dihydrochloride exhibits LDHB inhibitory activity with an EC50 value of 42 nM[1].
In vitro, AXKO-0046 exhibits potent and selective LDHB inhibitory activity with an EC50 value of 42 nM. It binds to a potential allosteric site away from the LDHB catalytic active site, inhibiting LDHB in an uncompetitive manner with respect to both NADH and pyruvate. This highly selective inhibition helps validate LDHB-associated pathways in cancer metabolism without affecting LDHA or other related enzymes. |
| ln Vivo |
Detailed in vivo efficacy data for AXKO-0046 dihydrochloride are not extensively reported in standard product data sheets. The primary research focus has been on in vitro enzyme inhibition and binding studies, establishing its role as a highly selective LDHB inhibitor for probing cancer metabolism pathways. Further in vivo studies would be required to evaluate its pharmacokinetic properties and therapeutic potential.
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| Enzyme Assay |
For AXKO-0046 dihydrochloride, a high-throughput mass spectrometry screening system was developed using an LDHB enzyme assay that detects NADH and NAD+ conversion. The compound is pre-incubated with LDHB for varying times (0-120 min) before initiating the reaction. X-ray crystallography is also employed to visualize binding to the allosteric site. Kinetic parameters (Km and Vmax) for NADH and pyruvate are measured to confirm uncompetitive inhibition.
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| Cell Assay |
For AXKO-0046 dihydrochloride, cancer cell lines (such as those dependent on LDHB for proliferation) are cultured and treated with the compound at varying concentrations. Cell viability is assessed using standard assays like MTT or CellTiter-Glo. LDHB inhibition in cells is confirmed by measuring lactate production or NADH/NAD+ ratios in cell lysates. EC50 for enzyme inhibition (42 nM) is measured in cell-free systems rather than whole-cell proliferation assays.
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| Animal Protocol |
For AXKO-0046 dihydrochloride, detailed in vivo animal model protocols are not extensively reported in standard product documentation. As a tool compound for studying cancer metabolism, in vivo studies would typically involve administration to tumor xenograft models to assess its effects on LDHB-associated pathways and tumor growth. Pharmacokinetic properties are likely to be evaluated prior to efficacy studies.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic properties for AXKO-0046 dihydrochloride are not extensively reported in standard product literature, as the compound is primarily used as a tool for in vitro studies of LDHB-associated cancer metabolism. As a small indole derivative, it may have favorable drug-like properties. Comprehensive PK studies would be required to evaluate parameters such as bioavailability, half-life, and tissue distribution for future in vivo applications.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for AXKO-0046 dihydrochloride are not extensively reported in available literature, as the compound is primarily used as a research tool. Standard safety assessments for in vitro and in vivo use should follow institutional guidelines for handling chemical inhibitors. For laboratory applications, typical precautions for indole derivatives apply, including appropriate personal protective equipment.
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| References | |
| Additional Infomation |
AXKO-0046 dihydrochloride was identified as the first highly selective inhibitor of human lactate dehydrogenase B through high-throughput mass spectrometry screening of 2,000 compounds. X-ray crystallography revealed that AXKO-0046 binds to a potential allosteric site away from the LDHB catalytic active site, targeting the tetramerisation interface of the two dimers. The compound and its derivatives can be used to validate LDHB-associated pathways in cancer metabolism, providing a valuable chemical probe for studying the Warburg effect and cancer cell metabolism.
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| Molecular Formula |
C25H35CL2N3
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| Molecular Weight |
448.47
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| Related CAS # |
AXKO-0046
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| Appearance |
Off-white to light yellow solid powder
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 :~50 mg/mL (~111.49 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.57 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 25.0 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: ≥ 2.5 mg/mL (5.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2298 mL | 11.1490 mL | 22.2980 mL | |
| 5 mM | 0.4460 mL | 2.2298 mL | 4.4596 mL | |
| 10 mM | 0.2230 mL | 1.1149 mL | 2.2298 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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