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Purity: ≥98%
NSC-663284 (also known as SPS-8I1; DA3003-1) is a novel and potent inhibitor of the Cdc25 dual specificity phosphatases and SETD8 with anticancer activity. It inhibits Cdc25 phosphatases with an IC50 of 0.21 μM. NSC 663284 blocked cellular Erk dephosphorylation caused by ectopic Cdc25A expression. The Cdc25 dual specificity phosphatases have central roles in coordinating cellular signaling processes and cell proliferation, but potent and selective inhibitors are lacking. DA3003-1 inhibited the growth of subcutaneous human colon HT29 xenografts in SCID mice. After a single i.v. dose of 5 mg/kg, DA3003-1 was not detectable in plasma or tissues beyond 5 min. In vitro studies showed that DA3003-1 was rapidly dechlorinated and conjugated to glutathione. Following DA3003-1 treatment of tumor-bearing SCID mice, reduced glutathione concentrations in HT29 tumor were decreased to a greater extent and remained decreased for longer than the reduced glutathione concentrations in liver and kidneys. These studies suggest that the minimal antitumor activity of DA3003-1 in mice may be due to its rapid metabolism.
| ln Vitro |
The NCI 60-cell human tumor panel showed a mean IC50 of 1.5 ± 0.6 μM for NSC 663284 (3-100 μM; 48 hours), while human breast cancer MDA-MB-435 and MDA-N cells had an IC50 of 0.2 μM. 1.7 μM is the IC50 value in human breast MCF-7 cells that have been grown [1]. NSC 663284's relative IC50 value for Cdc25B2 (IC50=0.21 μM) is greater than that of PTP1B (IC50>4.0 μM) or VHR (IC50=4.0 μM) [1].
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| ln Vivo |
The growth of human floating HT29 xenografts obtained via SCID intravenous subcutaneous injection is inhibited by NSC 663284 (iv; 2, 3, and 5 mg/kg). After a single dosage of 5 mg/kg, NSC 663284 was not identifiable in tissues or veins for more than five minutes. Glutathione levels in HT29 tumors decreased more and persisted longer following NSC 663284 treatment in tumor-bearing SCID mice than in kidney and liver cancer [3].
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| References |
[1]. Lazo JS, et al. Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatase Cdc25. J Med Chem. 2001 Nov 22;44(24):4042-9.
[2]. Coussens NP, et al. High-throughput screening with nucleosome substrate identifies small-molecule inhibitors of the human histone lysine methyltransferase NSD2. J Biol Chem. 2018 Aug 31;293(35):13750-13765. [3]. Guo J, et al. Pharmacology and antitumor activity of a quinolinedione Cdc25 phosphatase inhibitor DA3003-1 (NSC 663284). Anticancer Res. 2007 Sep-Oct;27(5A):3067-73 |
| Molecular Formula |
C15H16N3O3CL
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|---|---|
| Molecular Weight |
321.75884
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| CAS # |
383907-43-5
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| SMILES |
O=C(C(Cl)=C1NCCN2CCOCC2)C3=C(N=CC=C3)C1=O
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| InChi Key |
BMKPVDQDJQWBPD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H16ClN3O3/c16-11-13(18-4-5-19-6-8-22-9-7-19)15(21)12-10(14(11)20)2-1-3-17-12/h1-3,18H,4-9H2
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| Chemical Name |
6-Chloro-7-(2-morpholin-4-yl-ethylamino)quinoline-5,8-dione
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| Synonyms |
SPS8I1; DA30031; NSC-663284; SPS-8I1; DA3003 1;NSC 663284; SPS 8I1; DA3003-1; NSC663284;
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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 : ≥ 100 mg/mL (~310.79 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.77 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 (7.77 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 (7.77 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 | 3.1079 mL | 15.5395 mL | 31.0791 mL | |
| 5 mM | 0.6216 mL | 3.1079 mL | 6.2158 mL | |
| 10 mM | 0.3108 mL | 1.5540 mL | 3.1079 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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