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Purity: ≥98%
DASA-58 is a potent and selective activator of pyruvate kinase M2 (PKM2) with an AC90 value of 680 nM, and an AC50 value of 38 nM. DASA-58 inhibits LPS-induced Hif-1α and IL-1β, as well as the expression of a range of other Hif-1α-dependent genes in primary BMDMs, and also inhibits glycolysis and the accumulation of succinate in LPS-activated macrophages. In PC3 cells, DASA-58 impairs stromal-induced EMT program by restoring PK activity and abrogating the nuclear translocation of PKM2, as well as its association with HIF-1α.
| ln Vitro |
Other metabolic stresses' anticancer effects are enhanced by DASA-58 (15 μM; 2 h)[1]. In breast cancer cells, DASA-58 (15 μM; 24 h, 72 h) increases pyruvate kinase activity, but it has no discernible effect on proliferation [1]. Extracellular acidification and lactate levels are increased in BCa cell lines by DASA-58 (30 μM, 60 μM; 0-72 h); extracellular acidification levels are induced in prostate cancer cell lines[1]. In BCa cells, DASA-58 (15 μM, 30 μM; 0-72 h) alters respiration levels without showing any signs of mitochondrial damage[1]. DASA-58 (15 μM; 0-72 h) does not, in any combination, restore TXNIP levels, and PKM2 effects on AMPK signaling activation (T172 phosphorylation of AMPK) are enhanced by mitochondrial inhibitors [1]. DASA-58 (15 μM; 0-72 h) depletes upstream glycolytic intermediates rather than enhancing proteasomal degradation, which causes a decrease in TXNIP levels independent of AMPK and ER signaling[1].
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| ln Vivo |
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: Five breast cancer cell lines (BCa cells) (MDA MB 231, MDA MB 468, HCC 1443, T47-D, MCF7, LnCap, PC3, and DU145) Tested Concentrations: 15 μM Incubation Duration: 2 h Experimental Results: Could be exploited by other metabolic stressors. Western Blot Analysis[1] Cell Types: BCa cells Tested Concentrations: 15 μM Incubation Duration: 24 h, 72 h Experimental Results: demonstrated comparable PKM2 protein levels in five breast cancer cell lines, except HCC1443 cells and MDA MB 468 that demonstrated the highest and lowest PKM2 protein levels, respectively. Not changed PKM2 levels in five breast cancer cell lines but seemingly decreased TXNIP levels in cells expressing detectable TXNIP levels. |
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| References |
[1]. Fadi Almouhanna, et al. Pharmacological activation of pyruvate kinase M2 reprograms glycolysis leading to TXNIP depletion and AMPK activation in breast cancer cells. Cancer Metab. 2021 Jan 22;9(1):5.
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| Molecular Formula |
C19H23N3O6S2
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| Molecular Weight |
453.53
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| CAS # |
1203494-49-8
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| Related CAS # |
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| SMILES |
NC1=CC=CC(S(=O)(N2CCN(S(=O)(C3=CC=C(OCCO4)C4=C3)=O)CCC2)=O)=C1
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| InChi Key |
GMHIOMMKSMSRLY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H23N3O6S2/c20-15-3-1-4-16(13-15)29(23,24)21-7-2-8-22(10-9-21)30(25,26)17-5-6-18-19(14-17)28-12-11-27-18/h1,3-6,13-14H,2,7-12,20H2
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| Chemical Name |
3-[[4-[(2,3-dihydro-1,4-benzodioxin-6-yl)sulfonyl]hexahydro-1H-1,4-diazepin-1-yl]sulfonyl]-benzenamine
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.59 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 (4.59 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 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.59 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 | 2.2049 mL | 11.0246 mL | 22.0493 mL | |
| 5 mM | 0.4410 mL | 2.2049 mL | 4.4099 mL | |
| 10 mM | 0.2205 mL | 1.1025 mL | 2.2049 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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