SP-141 is a novel, cell-permeable, selective and high affinity MDM2 inhibitor (Ki = 28 nM) with excellent in-vitro and in-vivo anticancer activity. Directly binding to MDM2, SP 141 causes MDM2 autoubiquitination and proteasomal degradation in addition to inhibiting MDM2 expression. SP 141 has been shown to slow the growth of tumors created from breast cancer xenografts.
Physicochemical Properties
| Molecular Formula | C22H16N2O |
| Molecular Weight | 324.37524 |
| Exact Mass | 324.126 |
| Elemental Analysis | C, 81.46; H, 4.97; N, 8.64; O, 4.93 |
| CAS # | 1253491-42-7 |
| Related CAS # | 1253491-42-7 |
| PubChem CID | 59620153 |
| Appearance | White to yellow solid powder |
| LogP | 5.544 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 25 |
| Complexity | 469 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | COC1C=CC2=C(C3C=CN=C(C4=CC=CC5=CC=CC=C45)C=3N2)C=1 |
| InChi Key | AABFWJDLCCDJJN-UHFFFAOYSA-N |
| 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 |
| Chemical Name | 6-methoxy-1-naphthalen-1-yl-9H-pyrido[3,4-b]indole |
| Synonyms | SP-141; SP 141; SP141 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | MDM2 (IC50 < 0.50 μM) |
| 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] |
| 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. |
| 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). |
| References |
[1]. Identification of a New Class of MDM2 Inhibitor That Inhibits Growth of Orthotopic Pancreatic Tumors in Mice. Gastroenterology. 2014 Oct;147(4):893-902.e2. [2]. The Pyrido[b]indole MDM2 Inhibitor SP-141 Exerts Potent Therapeutic Effects in Breast Cancer Models. Nat Commun. 2014 Oct 1;5:5086. |
Solubility Data
| Solubility (In Vitro) |
DMSO: 65~125 mg/mL (200.4~385.4 mM) Ethanol: ~65 mg/mL (~200.4 mM) |
| 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 |