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| 25mg |
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Purity: ≥98%
SW044248 is a novel, potent and selective Topoisomerase I inhibitor that was identified through a screen for chemicals selectively toxic for non-small cell lung cancer (NSCLC) cell lines. It was discovered that in sensitive cells, but not in insensitive cells, SW044248 quickly inhibits macromolecular synthesis. A panel of 74 NSCLC cell lines was treated with SW044248, which was nontoxic to immortalized human bronchial cell lines and killed about 15% of them. SW044248 inhibited topoisomerase 1 (Top1) but not topoisomerase 2, and in sensitive HCC4017 cells, the acute transcriptional response to the drug correlated significantly with topoisomerase inhibitors. Camptothecin did not exhibit the same selective toxicity as SW044248, and SW044248 inhibited Top1 in a different way than camptothecin. Although deleting Top1 was eventually toxic, it did provide some protection against SW044248 for cells when done so via siRNA. siRNA to CDKN1A sensitized cells resistant to SW044248, and those cells upregulated CDKN1A in response to the compound. Thus, at least part of the differential sensitivity of NSCLC cells to SW044248 is the ability to upregulate CDKN1A.
| Targets |
Topoisomerase I
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| Cell Assay |
In wells of 96-well plates, 100 μL of 50,000 cells/mL cell suspensions of distinct cell lines are added. The following day, 100 μL of cell medium was added to each well, substituting 2X concentration of either SW044248, camptothecin, or DMSO in triplicate. The wells' ATP concentration is determined using CelTiter-Glo after 96 and 120 hours. With the aid of a plate reader, luminescence is measured[1].
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| References |
| Molecular Formula |
C22H23N5O2S
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| Molecular Weight |
421.52
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| Exact Mass |
421.157
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| Elemental Analysis |
C, 62.69; H, 5.50; N, 16.61; O, 7.59; S, 7.61
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| CAS # |
522650-83-5
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| Related CAS # |
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| PubChem CID |
3152990
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.675
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| LogP |
4.48
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
582
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1N=NC2=C(N=1)N(C([H])([H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C12)C([H])(C(N([H])C1=C([H])C([H])=C([H])C([H])=C1OC([H])([H])[H])=O)C([H])([H])C([H])([H])[H]
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| InChi Key |
PEVRGVRHMMZNGI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23N5O2S/c1-4-18(21(28)23-15-11-7-9-13-17(15)29-3)30-22-24-20-19(25-26-22)14-10-6-8-12-16(14)27(20)5-2/h6-13,18H,4-5H2,1-3H3,(H,23,28)
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| Chemical Name |
2-[(5-ethyl-[1,2,4]triazino[5,6-b]indol-3-yl)sulfanyl]-N-(2-methoxyphenyl)butanamide
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| Synonyms |
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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 |
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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: ≥ 1.25 mg/mL (2.97 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 12.5 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 | 2.3724 mL | 11.8618 mL | 23.7237 mL | |
| 5 mM | 0.4745 mL | 2.3724 mL | 4.7447 mL | |
| 10 mM | 0.2372 mL | 1.1862 mL | 2.3724 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.
 SW044248 rapidly inhibits RNA, DNA and protein synthesis in HCC4017 but not HBEC30KT cells.Mol Cancer Ther.2016 Jan;15(1):23-36. |
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 SW044248 and CPT inhibit Top1 differentially. A. SW044248 does not inhibit Top2.Mol Cancer Ther.2016 Jan;15(1):23-36. |
 Cells resistant to SW044248 increase p21CDKN1Aand cells sensitive to SW044248 do not.Mol Cancer Ther.2016 Jan;15(1):23-36. |
 SW044248 rapidly activates the integrated stress response through kinases GCN2 and PKR.Mol Cancer Ther.2016 Jan;15(1):23-36. |
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 siRNA knockdown of GCN2 or Top1 decreases the stress responses to SW044248.Mol Cancer Ther.2016 Jan;15(1):23-36. |
 SW044248 is selectively toxic for certain NSCLC cell lines.Mol Cancer Ther.2016 Jan;15(1):23-36. |
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