| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
GSK2837808A is a potent, selective, and an NADH-competitive inhibitor of lactate dehydrogenase A (LDHA) with IC50s of 1.9 and 14 nM for LDHA and LDHB, respectively. GSK2837808A rapidly and profoundly inhibited lactate production rates in multiple cancer cell lines including hepatocellular and breast carcinomas. Consistent with selective inhibition of LDHA, the most sensitive breast cancer cell lines to lactate inhibition in hypoxic conditions were cells with low expression of LDHB. GSK2837808A increased rates of oxygen consumption in hepatocellular carcinoma cells at doses up to 3 microM, while higher concentrations directly inhibited mitochondrial function. Analysis of more than 500 metabolites upon LDHA inhibition in Snu398 cells revealed that intracellular concentrations of glycolysis and citric acid cycle intermediates were increased, consistent with enhanced Krebs cycle activity and blockage of cytosolic glycolysis. Treatment with these compounds also potentiated PKM2 activity and promoted apoptosis in Snu398 cells.
| ln Vitro |
In certain cancer cell lines, such as those from hepatocellular carcinoma and breast cancer, GSK2837808A quickly and significantly reduces the rates at which lactate is produced. In thirty cancer cell lines with different levels of LDHA and LDHB expression, the potency of GSK2837808A varied from 400 nM to ineffective (EC50 reported as 30 μM). There was no correlation found between the potency of GSK2837808A and the levels of LDHA, LDHB, or total LDH expression. Under hypoxic conditions, GSK2837808A suppresses lactate synthesis, but at higher doses than in normoxic conditions (EC50=10 μM). Furthermore, it lowers ECAR (EC50=10 μM). Multiple metabolic pathways in Snu398 cells are altered when LDH is inhibited by GSK2837808A [1].
|
|---|---|
| ln Vivo |
Following intravenous infusion at a dose of 0.25 mg/kg in rats, the clearance rate of GSK2837808A was 69 mL/min/kg, exceeding the animal liver blood flow. Following oral administration of GSK2837808A at a dose of 50 mg/kg in rats and 100 mg/kg in mice, blood chemical levels were at or below the 2.5 ng/mL detection limit [1].
|
| References |
[1]. Billiard J, et al. Quinoline 3-sulfonamides inhibit lactate dehydrogenase A and reverse aerobic glycolysis in cancer cells. Cancer Metab. 2013 Sep 6;1(1):19
|
| Molecular Formula |
C31H25F2N5O7S
|
|
|---|---|---|
| Molecular Weight |
649.63
|
|
| CAS # |
1445879-21-9
|
|
| Related CAS # |
|
|
| SMILES |
O=C(O)C1=CC(OC2=CC(F)=CC(F)=C2)=CC(NC3=C(S(=O)(NC4CC4)=O)C=NC5=CC(C6=CN=C(OC) N=C6OC)=CC=C35)=C1
|
|
| Chemical Name |
|
|
| Synonyms |
|
|
| 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)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.85 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5393 mL | 7.6967 mL | 15.3934 mL | |
| 5 mM | 0.3079 mL | 1.5393 mL | 3.0787 mL | |
| 10 mM | 0.1539 mL | 0.7697 mL | 1.5393 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.
Quinoline 3-sulfonamides inhibit lactate dehydrogenase A (LDHA) and reduce lactate production in cancer cells.Cancer Metab.2013 Sep 6;1(1):19. |
|---|
Lactate dehydrogenase A (LDHA) inhibitor induces profound metabolic changes in Snu398, but not HepG2 hepatocellular carcinoma cells.Cancer Metab.2013 Sep 6;1(1):19. |
Compound 1 causes increase in pyruvate kinase (PK) activity.Cancer Metab.2013 Sep 6;1(1):19. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
