477-47-4

Basic information

• Product Name: (-)PPP
• Synonyms: PICROPODOPHYLLIN;(-)PPP;POLY(2,5-BIS(3-SULFONATOPROPOXY)-1,4-PHENYLENE, DISODIUM SALT-ALT-1,4-PHENYLENE);NSC 36407, Picropodophyllin, PPP, (5R,5aS,8aR,9R)-9-Hydroxy-5,8,8a,9-tetrahydro-5-(3,4,5-trimethoxyphenyl)furo[3μ,4μ:6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one;(5R,5aS,8aR,9R)-5,8,8a,9-Tetrahydro-9-hydroxy-5-(3,4,5-trimethoxyphenyl)-furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one;IGF-1R Inhibitor, PPP;(5R,5aS,8aR,9R)-9-Hydroxy-5,8,8a,9-tetrahydro-5-(3,4,5-trimethoxyphenyl)fur[3′,4′:6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one;NSC 36407
• CAS NO: 477-47-4
• Molecular Formula: C₂₂H₂₂O₈
• Molecular Weight: 414.40528
• Product Categories: Insulin-like Growth Factor-1 Receptor Inhibitor;Picropodophyllin
• Mol File: 477-47-4.mol
• Article Data: 30

Chemical Properties

• Melting Point: 225-227℃
• Boiling Point: 453.31°C (rough estimate)
• Flash Point: 210.2°C
• Appearance: white/
• Density: 1.370
• Refractive Index: 1.4480 (estimate)
• Storage Temp.: 2-8°C
• Solubility: H2O: soluble
• PKA: 13.26±0.40(Predicted)
• Sensitive: Light Sensitive
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.
• CAS DataBase Reference: (-)PPP(CAS DataBase Reference)
• NIST Chemistry Reference: (-)PPP(477-47-4)
• EPA Substance Registry System: (-)PPP(477-47-4)

Safety Data

• Hazard Codes: Xi,T
• Statements: 36/37/38-68-25-21
• Safety Statements: 26-36-45-36/37
• RIDADR: UN 3462 6.1/PG 2
• WGK Germany: 3
• RTECS: LV2510000
• HazardClass: 6.1
• Hazardous Substances Data: 477-47-4(Hazardous Substances Data)

Usage

Description

Picropodophyllotoxin (477-47-4) is a potent and selective inhibitor of insulin-like growth factor 1 receptor (IGF1R) which is non-competitive with ATP.1?Displays no activity at IR, EGFR, FGFR or PDGFR. Inhibits IGF1R autophosphorylation IC50 ~ 1 nM.1?Displays antiproliferative activity in numerous tumor cell lines, IC50 = 0.05 – 15 μM.2 Exhibits antiangiogenic activity.3?Picropodophyllotoxin attenuates intimal hyperplasia after vascular injury.4?Active in vivo.

Uses

Different sources of media describe the Uses of 477-47-4 differently. You can refer to the following data:
1. Insulin growth factor 1 receptor inhibitor, antineoplastic
2. Picropodophyllotoxin is an insulin-like growth factor-I (IGF-I) receptor kinase inhibitor

Definition

ChEBI: An organic heterotetracyclic compound that has a furonaphthodioxole skeleton bearing 3,4,5-trimethoxyphenyl and hydroxy substituents.

General Description

Poly(2,5-bis(3-sulfonatopropoxy)-1,4-phenylene, disodium salt-alt-1,4-phenylene) (PPP-OPSO3) is a water soluble conjugating polymer that can be used as a donor molecule. It has a poly(p-phenylene) skeleton with each repeating unit having two phenylene groups. It can be used for a variety of optoelectronic applications.

Biological Activity

Orally active insulin-like growth factor 1 receptor (IGF1R) inhibitor that exhibits no activity at the insulin receptor, FGFR, PDGFR or EGFR. Inhibits IGF1R autophosphorylation (IC 50 ~ 1 nM), increases the fraction of cells in the G 2 /M phase and upregulates apoptosis. Exhibits antiproliferative effects in multiple cancer cell lines (IC 50 = 0.05 - 15 μ M), and has anticancer and antineovascularization activity in vivo .

Biochem/physiol Actions

Picropodophyllotoxin (PPP), an epimer of podophyllotoxin (PPT), has been reported to target insulin-like growth factor-I receptor (IGF-IR) and mediate anticancer functions. However, a study in 2007, has reported that PPP can induce G2-M cell cycle arrest even in IGF-IR deficient cells. Hence, the role of PPP in IGF-IR-mediated anticancer functions is debatable.

References

1) Girnita et al. (2004), Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth; Cancer Res., 64 236 2) Girnita et al. (2006), The insulin-like growth factor-I receptor inhibitor picropodophyllin causes tumor regression and attenuates mechanisms involved in invasion of iveal melanoma cells; Clin. Cancer Res., 12 1383 3) Menu et al. (2007), Targeting the IGF-1R using picropodophyllin in therapeutical 5T2MM mouse model of multiple myeloma: beneficial effects on tumor growth, angiogenesis, bone disease and survival; Int. J. Cancer, 121 1857 4) Razuvaev et al. (2007), The cyclolignan picropodophyllin attenuates intimal hyperplasia after rat carotid balloon injury by blocking insulin-like growth factor-1 receptor signaling; J. Vasc. Surg., 46 108

Upstream product

• 186581-53-3 diazomethane 
• 112066-16-7 4'-O-demethylpicropodophyllotoxin 
• 77-78-1 dimethyl sulfate 
• 40505-27-9 4-demethylpodophyllotoxin 
• 7647-01-0 hydrogenchloride 
• 64-19-7 acetic acid 
• 344585-17-7 α-apopicropodophyllotoxin 
• 78216-05-4 picropodophyllic acid hydrazide 
• 7732-18-5 water 
• 75404-00-1 ethyl rel-(3R,4R)-6,7-methylenedioxy-1-oxo-4-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydronaphthalene-3-carboxylate 
• 120-57-0 piperonal 
• 477-67-8 (+/-)-isopodophyllinic acid 
• 1256-91-3 (5S,6R,7R,8S)-8-Hydroxy-7-hydroxymethyl-5-(3,4,5-trimethoxy-phenyl)-5,6,7,8-tetrahydro-naphtho[2,3-d][1,3]dioxole-6-carboxylic acid methyl ester 
• 4375-07-9 epipodophyllotoxin 

Downstream Products

• 47789-93-5 O-(3-Carboxy-propionyl)-picropodophyllin 
• 38491-90-6 (5R,5aR,8aS,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl acetate 
• 78215-98-2 benzoylpicropodophyllin 
• 37158-54-6 (5aS)-5c-(2-bromo-3,4,5-trimethoxy-phenyl)-9c-hydroxy-(5ar,8ac)-5,8,8a,9-tetrahydro-5aH-furo[3',4';6,7]naphtho[2,3-d][1,3]dioxol-6-one 
• 7470-99-7 2-(3,4,5-Trimethoxybenzoyl)-4,5-(methylenedioxy)benzoic Acid 
• 42123-13-7 7-(3,4,5-trimethoxy-phenyl)-7H-[1,3]dioxolo[4,5-f]isobenzofuran-5-one 
• 6258-41-9 5-(3,4,5-Trimethoxy-phenyl)-8H-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6-one 
• 4354-75-0 8-hydroxy-7-hydroxymethyl-5-(3,4,5-trimethoxy-phenyl)-5,6,7,8-tetrahydro-naphtho[2,3-d][1,3]dioxole-6-carboxylic acid 
• 344585-17-7 α-apopicropodophyllotoxin 
• 477-48-5 (5aR,8aS,9R)-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxole-5,8-dione 
• 245321-94-2 picropodophyllotoxin ethyl ether 
• 59123-24-9 (±)-β-apopicropodophyllin 
• 477-51-0 deoxypicropodophyllotoxin 
• 108448-52-8 (+)-4-O-(tert-butyldimethylsilyl)picropodophyllin 

Relevant articles and documents

Catalytic Enantioselective Synthesis of (-)-Podophyllotoxin

The first catalytic enantioselective total synthesis of (-)-podophyllotoxin is accomplished by a challenging organocatalytic cross-aldol Heck cyclization and distal stereocontrolled transfer hydrogenation in five steps from three aldehydes. Reversal of se

Insight into dihalogenation of E-ring of podophyllotoxins, and their acyloxyation derivatives at the C4 position as insecticidal agents

Unexpected sequential E-ring dihalogenation of podophyllotoxin analogues is reported. It demonstrated that a chlorine/bromine atom was prior introduced at the C2′ position of podophyllotoxin, and the corresponding free rotation of E-ring around the C1-C1′

Synthesis and quantitative structure-activity relationship (QSAR) study of novel isoxazoline and oxime derivatives of podophyllotoxin as insecticidal agents

In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, 33 isoxazoline and oxime derivatives of podophyllotoxin modified in the C and D rings were synthesized and their structures were characterized by Proton nuclear magnetic resonance ( 1H NMR), high-resolution mass spectrometry (HRMS), electrospray ionization-mass spectrometry (ESI-MS), optical rotation, melting point (mp), and infrared (IR) spectroscopy. The stereochemical configurations of compounds 5e, 5f, and 9f were unambiguously determined by X-ray crystallography. Their insecticidal activity was evaluated against the pre-third-instar larvae of northern armyworm, Mythimna separata (Walker), in vivo. Compounds 5e, 9c, 11g, and 11h especially exhibited more promising insecticidal activity than toosendanin, a commercial botanical insecticide extracted from Melia azedarach. A genetic algorithm combined with multiple linear regression (GA-MLR) calculation is performed by the MOBY DIGS package. Five selected descriptors are as follows: one two-dimensional (2D) autocorrelation descriptor (GATS4e), one edge adjacency indice (EEig06x), one RDF descriptor (RDF080v), one three-dimensional (3D) MoRSE descriptor (Mor09v), and one atom-centered fragment (H-052) descriptor. Quantitative structure-activity relationship studies demonstrated that the insecticidal activity of these compounds was mainly influenced by many factors, such as electronic distribution, steric factors, etc. For this model, the standard deviation error in prediction (SDEP) is 0.0592, the correlation coefficient (R2) is 0.861, and the leave-one-out cross-validation correlation coefficient (Q2 loo) is 0.797.