| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
MDM2 (IC50 < 0.50 μM)
SP-141 directly binds to MDM2, a negative regulator of the tumor suppressor p53. By binding to MDM2, SP-141 promotes its auto-ubiquitination and subsequent degradation by the proteasome. This reduces MDM2 levels, leading to the activation of p53 and the induction of apoptosis, even in cancer cells with mutant p53, due to alternative pathways. |
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| ln Vitro |
SP141 can bound directly to MDM2, promoting its auto-ubiquitination and degradation by the proteasome. With 50% inhibitory concentrations <0.5 μM (0.38–0.50 μM), SP141 decreases MDM2 levels in pancreatic cancer cell lines as well as their proliferation. Regardless of whether pancreatic cancer cell lines expressed functional P53, increasing SP141 concentrations cause an increase in apoptosis and G2-M phase arrest. [1]
In vitro, SP-141 directly binds to MDM2 with a Ki of 28 nM. It promotes MDM2 auto-ubiquitination and degradation. It induces pancreatic cancer cell death with IC50 values of 0.38-0.5 µM and inhibits MDM2 expression regardless of the p53 status of the cells, demonstrating p53-independent effects as well. |
| ln Vivo |
SP-141 (40 mg/kg; administered by i.p. injection; 5 d/wk for about three weeks) inhibits the development of pancreatic tumors In orthotopic and xenograft mouse models.
In vivo, SP-141 has shown potent therapeutic effects in breast cancer models. It inhibits the proliferation and tumor formation of pancreatic cancer cells in nude mice. Its ability to promote MDM2 degradation makes it a promising anticancer agent, with tumor growth inhibition observed in xenograft studies. |
| Enzyme Assay |
In vitro binding assays for SP-141 typically measure its affinity for MDM2 using techniques such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The compound's Ki of 28 nM is determined using these methods. Its ability to promote MDM2 ubiquitination can be assessed in cell-free ubiquitination assays using purified components.
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| Cell Assay |
The human pancreatic cancer cell lines HPAC, Panc-1, AsPC-1, and Mia-Paca-2 are subjected to various SP141 concentrations or vehicle controls. The effects of SP141 on cell viability, colony formation, proliferation (BrdUrd incorporation assay), apoptosis, and cell cycle distribution are then assessed using cells (MTT assay, colony formation, proliferation, 39, and cell proliferation).
In vitro cellular assays for SP-141 involve treating cancer cell lines (e.g., pancreatic, breast) with the compound and measuring MDM2 levels (by Western blot), p53 activity (by reporter assay or target gene expression), cell viability (by MTT or CCK-8), and apoptosis (by flow cytometry). The compound's ability to induce MDM2 degradation and cancer cell death is assessed. |
| Animal Protocol |
In vivo animal models for SP-141 include xenograft tumor models of pancreatic and breast cancer in immunocompromised mice. The compound is administered via intraperitoneal or oral routes, and tumor growth inhibition (volume measurement) and MDM2 levels in tumor tissue are assessed. Pharmacokinetic and toxicity studies are also conducted.
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| ADME/Pharmacokinetics |
SP-141 has a molecular formula of C22H16N2O and a molecular weight of 324.37 g/mol. Its chemical name is 6-methoxy-1-(naphthalen-1-yl)-9H-pyrido[3,4-b]indole. It is a cell-permeable MDM2 inhibitor. The compound is soluble in DMSO and DMF and should be stored as a powder at -20°C.
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| Toxicity/Toxicokinetics |
SP-141 is an MDM2 inhibitor with a well-characterized mechanism of action. As with any anticancer agent, potential toxicity may include effects on normal cell proliferation. In preclinical studies, it has shown acceptable safety profiles, but it is for research use only and is not approved for human therapeutic use.
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| References | |
| Additional Infomation |
An MDM2 inhibitor with antitumor activity; structure described in the first article.
SP-141 is a novel, cell-permeable, and selective MDM2 inhibitor with a Ki of 28 nM. It promotes MDM2 auto-ubiquitination and degradation and has shown anticancer activity in pancreatic and breast cancer models. The compound is for research use only and is not approved for human therapeutic use. |
| Molecular Formula |
C22H16N2O
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|---|---|
| Molecular Weight |
324.37524
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| Exact Mass |
324.126
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| Elemental Analysis |
C, 81.46; H, 4.97; N, 8.64; O, 4.93
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| CAS # |
1253491-42-7
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| Related CAS # |
1253491-42-7
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| PubChem CID |
59620153
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| Appearance |
White to yellow solid powder
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| LogP |
5.544
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
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| Complexity |
469
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1C=CC2=C(C3C=CN=C(C4=CC=CC5=CC=CC=C45)C=3N2)C=1
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| InChi Key |
AABFWJDLCCDJJN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H16N2O/c1-25-15-9-10-20-19(13-15)18-11-12-23-21(22(18)24-20)17-8-4-6-14-5-2-3-7-16(14)17/h2-13,24H,1H3
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| Chemical Name |
6-methoxy-1-naphthalen-1-yl-9H-pyrido[3,4-b]indole
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| Synonyms |
SP-141; SP 141; SP141
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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: 65~125 mg/mL (200.4~385.4 mM)
Ethanol: ~65 mg/mL (~200.4 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.41 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 (6.41 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 20.8 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 | 3.0828 mL | 15.4140 mL | 30.8280 mL | |
| 5 mM | 0.6166 mL | 3.0828 mL | 6.1656 mL | |
| 10 mM | 0.3083 mL | 1.5414 mL | 3.0828 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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