| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
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| Targets |
SOD1 1.07 μM (IC50)
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|---|---|
| ln Vitro |
HCT116 cells that express the bloom syndrome gene product (BLM) or lack it are specifically cytotoxic to LCS-1 (1–10,000 nM; 24 hours) [1]. LCS-1 targets normal human bronchial epithelial (NHBE) cells (IC 50=2.66 μM) and 10/27 adenocarcinoma cell lines (median IC50=0.20 μM; such as H23, H2347, and HCC827 cell lines) [2]. In multiple myeloma (MM) cells, LCS-1 (0, 1.25, 2 μM; 4 hours) significantly inhibits SOD1 enzymatic activity in a concentration-dependent manner [3]. The viability of other MM cell lines, such as MM.1R (dexamethasone-resistant), Dox40 (doxorubicin-resistant), or LR5 (melphalan-resistant), is reduced in a dose-dependent manner by LCS-1 (0, 1.25, 2.5, and 5 μM; 48 hours) [3]. LCS-1 (48 hours) had an IC50 value of 2.5 and 4.6 μM, respectively, on the viability of ANBL6-WT (bortezomib-sensitive) and ANBL6-BR (bortezomib-resistant) cells [3]. In MM.1S cells, LCS-1 (1.25 μM; 16 h) dramatically raised ROS and O2 levels [3]. In MM.1S cells, LCS-1 (1.25 μM; 16 hours) significantly reduced the GSH/GSSG ratio [3]. In MM.1S cells, LCS-1 (1.25 μM; 24 hours) enriches proteins that mediate mtUPR signaling (HSP60/CLPP) and stimulates the release of mitochondrial cytochrome-c into the cytosol [3]. RP2CP is activated by LCS-1-induced O2 (1.25 μM; 5 hours), and RP dramatically lowers the CP form of the 126S proteasome [3]. MM.1S cells undergo both early and late apoptosis when exposed to LCS-1 (2 μM; 16 hours) [3]. In MM.1S cells, LCS-1 (0, 0.5, 1, 1.5, or 2 μM) downregulates MCL-1, BclxL, or c-Myc and upregulates p53/p21 signaling [3]. When applied to mitochondrial unfolded protein response (UPR) proteins (BIP, PERK, phosphorylated eIF2α, or lectin proteins) in MM.1S and ANBL6-BR cells, LCS-1 (0, 4, 8, 16, 24 hours; 2 μM) demonstrates a strong and quick induction [3].
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| ln Vivo |
In mice harboring MM.1S, LCS-1 (20 mg/kg; intraperitoneally given every other day for 14 days) suppresses MM growth and prolongs host survival [3].
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: BLM-proficient and BLM-deficient HCT116 cells Tested Concentrations: 1-10000 nM Incubation Duration: 24 hrs (hours) Experimental Results: Had IC50 values of 1462 nM and 24.92 nM for the viability of BLM-proficient and BLM-deficient HCT116 cells, respectively. Western Blot Analysis[3] Cell Types: MM.1S and ANBL6-BR cells Tested Concentrations: 2 μM Incubation Duration: 16 hrs (hours) Experimental Results: diminished the expression of cell-cycle regulatory proteins (cyclin-B1, CDC25C, and CDC2). Western Blot Analysis[3] Cell Types: MM.1S cells Tested Concentrations: 0, 0.5, 1, 1.5, 2 μM Incubation Duration: Experimental Results: Upregulated p53/p21 signaling, as well as downregulated survival pathway proteins MCL-1, BclxL, or c-Myc. Western Blot Analysis[3] Cell Types: MM.1S cells Tested Concentrations: 2 μM Incubation Duration: 0, 4, 8, 16, 24 hrs (hours) Experimental Results: demonstrated a rapid and robust induction of UPR proteins (BIP, PERK, phosphorylated eIF2α, or a lectin protein calnexin). |
| Animal Protocol |
Animal/Disease Models: 5weeks old female CB17 SCID (severe combined immunodeficient) mouse (MM.1S tumors volume=100 mm3)[3]
Doses: 20 mg/kg (diluted in saline) Route of Administration: intraperitoneal (ip)injections; treated on an every other day schedule for 14 days Experimental Results: Inhibited MM growth and prolongs host survival. |
| References |
|
| Molecular Formula |
C11H8CL2N2O
|
|---|---|
| Molecular Weight |
255.10
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| Exact Mass |
254.001
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| CAS # |
41931-13-9
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| PubChem CID |
779573
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| Appearance |
Light yellow to light brown solid powder
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| Density |
1.39g/cm3
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| Boiling Point |
339.6ºC at 760 mmHg
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| Flash Point |
159.2ºC
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| Index of Refraction |
1.627
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| LogP |
2.847
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
16
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| Complexity |
365
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
SYUPLLHVMCLXEM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H8Cl2N2O/c1-7-3-2-4-8(5-7)15-11(16)10(13)9(12)6-14-15/h2-6H,1H3
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| Chemical Name |
4,5-dichloro-2-(3-methylphenyl)pyridazin-3-one
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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) |
DMSO : 50 mg/mL (196.00 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.80 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 25.0 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 | 3.9200 mL | 19.6002 mL | 39.2003 mL | |
| 5 mM | 0.7840 mL | 3.9200 mL | 7.8401 mL | |
| 10 mM | 0.3920 mL | 1.9600 mL | 3.9200 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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