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Picropodophyllin

HCID 72435
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Basic information

CAS
477-47-4
Standard SMILES
COc1cc([C@@H]2c3cc4c(cc3[C@H](O)[C@H]3COC(=O)[C@@H]23)OCO4)cc(OC)c1OC
InChIKey
YJGVMLPVUAXIQN-HAEOHBJNSA-N
Molecular formula
C22H22O8
Average molar mass
414.4 g/mol
Monoisotopic mass
414.13146766

Overview

Picropodophyllotoxin is an organic heterotetracyclic compound that has a furonaphthodioxole skeleton bearing 3,4,5-trimethoxyphenyl and hydroxy substituents. It has a role as an antineoplastic agent, a tyrosine kinase inhibitor, an insulin-like growth factor receptor 1 antagonist and a plant metabolite. It is a lignan, an organic heterotetracyclic compound and a furonaphthodioxole.

Names & identifiers

Preferred name
Picropodophyllin
IUPAC
(5R,5aR,8aS,9R)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
English name
(-)PPP
Molecular formula
C22H22O8
Molecular weight
414.41

Names & synonyms

PicropodophyllinPicropodophyllotoxin477-47-4AXL1717cyclolignan PPPpicro-podophyllinAXL-1717Picropodophyllin (PPP)0F35AOI227NSC36407NSC-36407Podophyllotoxin picropodophyllin
Show more names
Metacavir(-)PPP(-)PPPAXL 1717NSC 36407(-)PPP USP/EP/BPPictopodophyllotoxin
(5R,5aR,8aS,9R)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-oneCHEBI:75251DTXSID80197245(5R,5aR,8aS,9R)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-(2)benzofuro(5,6-f)(1,3)benzodioxol-8-oneRefChem:174194DTXCID90119736Furo(3',4':6,7)naphtho(2,3-d)-1,3-dioxol-6(5aH)-one,5,8,8a,9-tetrahydro-9-hydroxy-5-(3,4,5-trimethoxyphenyl)-,(5R-(5-alpha,5a-alpha,8a-alpha,9-alpha))-17434-18-3

Database identifiers

CAS
477-47-4
PubChem CID
72435
DTXSID
DTXSID80197245

Properties

Computed structural properties

XLogP
2
Topological polar surface area
92.7 Ų
Hydrogen bond donors
1
Hydrogen bond acceptors
8
Rotatable bonds
4
Heavy atoms
30
Formal charge
0
Complexity
629

Experimental & physicochemical properties

DrugsPharmaceuticals -> Listed in ZINC15
Endocrine DisruptorsPotential endocrine disrupting compound
Collision Cross Section · 2 items

189.52 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

190.9 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Physicochemical properties

Melting point
225 · 225-227℃
alpha
20 · D20 +9.4° (c = 0.7 in chloroform)
Boiling point
453.31 °C · 453.31°C (rough estimate)
Density
1.37 · 1.370
refractive index
1.448 · 1.4480 (estimate)
storage temp.
2 · Sealed in dry,2-8°C
solubility
2 O: · H2O: soluble
form
powder
pka

Safety & regulation

Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.

GHS classification

GHS Classification · 4 items

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P317, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 41 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Hazard information

Hazard Classes and CategoriesAcute Tox. 3 (100%)

Toxicology

Exposure RoutesTopical application of 0.05 mL of 0.5% podofilox solution to external genitalia did not result in detectable serum levels. Applications of 0.1 to 1.5 mL resulted in peak serum levels of 1 to 17 ng/mL one to two hours after application.
Toxicity Summary · 1 item

Etoposide, a semisynthetic derivative of podofilox, induces DNA breakage through its inhibition of topoisomerase II. The drug is most active in the late S and early G2 phases of the cell cycle. Teniposide is an analog with very similar pharmacologic characteristics. Podofilox derivatives display binding activity to the enzyme topoisomerase II during the late S and early G2 stage. For instance, etoposide binds and stabilizes the temporary break caused by the enzyme, disrupts the reparation of the break through which the double-stranded DNA passes, and consequently stops DNA unwinding and replication. Mutants resistant to either podofilox, or to its topoisomerase II inhibitory derivatives such as etoposide (VP-16), have been described in Chinese hamster cells. The mutually exclusive cross-resistance patterns of these mutants provide a highly specific mean to distinguish the two kinds of podofilox derivatives. Mutant Chinese hamster cells resistant to podofilox are affected in a protein P1 that was later identified as the mammalian HSP60 or chaperonin protein. (Wikipedia)

Chemistry & industry

Pharmacology

Metabolism/MetabolitesHalf Life: 1.0 to 4.5 hours.

Uses & manufacturing

UsesFor treatment of external genital warts (<i>Condyloma acuminatum</i>).
Applications · 4 items

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

UsesInsulin growth factor 1 receptor inhibitor, antineoplastic

UsesPicropodophyllotoxin is an insulin-like growth factor-I (IGF-I) receptor kinase inhibitor

General DescriptionPoly(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.

Additional notes

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

Related reactions

2 records
New reaction record
HRID 1285477 reaction equation
HRID 1285477As reactantuspto-grants-1986_01
HRID 1285478 reaction equation
HRID 1285478As productAs reactantuspto-grants-1986_01

Compound notes

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On this pageBasic informationOverviewNames & identifiersPropertiesSafety & regulationChemistry & industryRelated reactionsCompound notes
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ChEMBL
CHEMBL283120
ChEBI
CHEBI:75251
UNII
0F35AOI227
EC Number
637-166-4
Nikkaji
J112.698I
13.26 · 13.26±0.40(Predicted)
color
white
Water Solubility
2 O: · H2O: soluble
λmax
208 nm · 208 nm (in deoxygenated water)(lit.)
Sensitive
Light Sensitive
Stability
1 year · Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.
InChIKey
YJGVMLPVUAXIQN-HAEOHBJNSA-N
SMILES
O1C2=CC3=C(C=C2OC1)[C@@H](C1=CC(OC)=C(OC)C(OC)=C1)[C@]1([H])C(=O)OC[C@]1([H])[C@H]3O
FDA UNII
0 F35AOI227 · 0F35AOI227
NCI Drug Dictionary
picropodophyllin
UNSPSC Code
12352200 · 12352200
NACRES
77 · NA.77
Symbol(GHS)
6 · GHS06
Signal word
Danger
Hazard statements
301 · H301-H312-H315-H319-H335
Precautionary statements
261 · P261-P264-P280-P301+P310-P302+P352+P312-P305+P351+P338
target organs
Respiratory system
Hazard Codes
Xi,T
Risk Statements
36 · 36/37/38-68-25-21
Safety Statements
26 · 26-36-45-36/37
RIDADR
3462 · UN 3462 6.1/PG 2
WGK Germany
3 · 3
RTECS
2510000 · LV2510000
HazardClass
6.1 · 6.1
Storage Class
6.1 C · 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
Hazard Classifications
3 OralAcute · Acute Tox. 3 OralAcute Tox. 4 DermalEye Irrit. 2Skin Irrit. 2STOT SE 3
Toxicity
50 intraperitoneal · LD50 intraperitoneal in mouse: 280mg/kg
Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).

Safety data

wgk
3
rtecs
LV2510000
ridadr
UN 3462 6.1/PG 2
Toxicity
LD50 intraperitoneal in mouse: 280mg/kg
risk_code
36/37/38-68-25-21
Signal word
Danger
Symbol(GHS)
GHS06
hazard_code
Xi,T
safety_code
26-36-45-36/37
hazard_class
6.1
Storage Class
6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
target organs
Respiratory system
Hazard statements
H301-H312-H315-H319-H335
Hazard Classifications
Acute Tox. 3 OralAcute Tox. 4 DermalEye Irrit. 2Skin Irrit. 2STOT SE 3
Precautionary statements
P261-P264-P280-P301+P310-P302+P352+P312-P305+P351+P338