1253491-42-7

Basic information

• Product Name: SP-141
• CAS NO: 1253491-42-7
• Molecular Weight: 324.382
• Mol File: 1253491-42-7.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 571.2±45.0 °C(Predicted)
• Density: 1.284±0.06 g/cm3(Predicted)
• CAS DataBase Reference: SP-141(CAS DataBase Reference)
• NIST Chemistry Reference: SP-141(1253491-42-7)
• EPA Substance Registry System: SP-141(1253491-42-7)

Safety Data

• Hazardous Substances Data: 1253491-42-7(Hazardous Substances Data)

Usage

Description

Mouse double minute 2 protein (MDM2) is an E3 ubiquitin-protein ligase that binds and ubiquitinates the tumor suppressor p53, leading to its degradation by the proteasome. SP 141 is a cell-permeable inhibitor of MDM2 (Ki = 28 nM). Binding of MDM2 by SP 141 promotes its auto-ubiquitination and proteasomal degradation. SP 141 induces cell cycle arrest and apoptosis in breast and pancreatic cancer cell lines and inhibits xenograft tumor growth in vivo. This compound has a short half-life in plasma and wide tissue distribution in tumor-bearing nude mice.

Uses

SP 141 induces cell cycle arrest and apoptosis in breast and pancreatic cancer cell lines, inhibiting xenograft tumor growth in vivo.

references

[1]. vassilev lt, vu bt, graves b, et al. in vivo activation of the p53 pathway by small-molecule antagonists of mdm2. science. 2004 feb 6;303(5659):844-8.[2]. wang w, qin jj, voruganti s, et al. the pyrido[b]indole mdm2 inhibitor sp-141 exerts potent therapeutic effects in breast cancer models. nat commun. 2014 oct 1;5:5086.[3]. wang w, qin jj, voruganti s, et al. 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.[4]. nag s, qin jj, voruganti s, et al. development and validation of a rapid hplc method for quantitation of sp-141, a novel pyrido[b]indole anticancer agent, and an initial pharmacokinetic study in mice. biomed chromatogr. 2015 may;29(5):654-63.

Upstream product

• 66-83-1 5-methoxytryptamine hydrochloride 
• 66-77-3 1-naphthaldehyde 
• 608-07-1 2-(5-methoxyindol-3-yl)ethylamine 

Relevant articles and documents

Feasibility of developing radiotracers for mdm2: Synthesis and preliminary evaluation of an18 f‐labeled analogue of the mdm2 inhibitor sp‐141

Murine double minute 2 (MDM2), a negative regulator of the p53 tumor suppressor pro-tein, is overexpressed in several human cancers. Herein we investigate the feasibility of developing 18 F‐labeled compounds based on the small molecule inhibitor SP‐141 for imaging tumor MDM2 expression levels with positron emission tomography (PET). Three nonradioactive fluorinated SP‐141 analogues, 1–3, were synthesized, and their binding to the MDM2 protein was analyzed by surface plasmon resonance (SPR). One of these, a fluoroethoxy analogue, was labeled with fluorine‐18 (18F) using18F‐fluorethyl bromide to provide [18F]1 and evaluated in vitro and in vivo. SPR analysis con-firmed the binding of the fluorinated analogues to MDM2 at 1.25–20 μM concentrations. Cell uptake studies revealed high uptake (67.5–71.4 %/mg protein) and specificity of [18F]1 in MCF7 and HepG2 cells. The uptake of [18F]1 in these cells could be modulated using 100 μM SP‐141, potentially reflect-ing changes in MDM2 expression because of p53 activation by SP‐141. [18 F]1 exhibited stable uptake and retention in HepG2 tumor xenografts (~3 %ID/g) in vivo, but poor clearance from blood and other normal tissues, yielding low tumor‐to‐background ratios (18F]1 has suboptimal characteristics for in vivo evaluation as a PET tracer for MDM2, but warrant radiolabeling and assessment of the other fluorinated analogues synthesized in this work, 2 and 3, and potentially other molecular scaffolds for developing MDM2 targeted radiotrac-ers.

1-ARYL OR 1-HETEROARYL-PYRIDO[B]INDOLES AND USES THEREOF

Provided herein are 1-aryl or 1-heteroarylsubstituted phenanthrene diketo acid compounds. These compounds comprise a β-carboline ring structure substituted at C1 with an aryl or heteroaryl moiety and individually substituted at C3-C8 and N9 with a C1-C4 alkyl, a C1-C4 alkoxy, a C1-C4 alkoxyphenyl, halogen, thiol, alkylthiol, sulfonyl, sulfomainde, amide, substituted amide, ester, nitrile, OH, amino, substituted amine, haloalkyl, haloalkoxy, acyl, or a hydrogen. Also provided are methods for inhibiting proliferation of a cancer cell or for treating a cell proliferative disease by contacting the cancer cell or tumor comprising the same with the compounds provided herein or by administering the compounds to a subject with a cell proliferative disease.