PODOFILOX

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H22O8
Molecular Weight	414.4061
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COc1cc(cc(c1OC)OC)[C@]2([H])c3cc4c(cc3[C@@]([H])([C@@]5([H])COC(=O)[C@@]52[H])O)OCO4

InChI

InChIKey=YJGVMLPVUAXIQN-XVVDYKMHSA-N

InChI=1S/C22H22O8/c1-25-16-4-10(5-17(26-2)21(16)27-3)18-11-6-14-15(30-9-29-14)7-12(11)20(23)13-8-28-22(24)19(13)18/h4-7,13,18-20,23H,8-9H2,1-3H3/t13-,18+,19-,20-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=affc1058-7355-4486-8b65-378fea6f9454
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/?term=9562603 http://products.sanofi.ca/en/condyline.pdf

Podofilox ((abbreviated as PPT), otherwise known as podofilox) is an antimitotic drug which can be chemically synthesized or purified from the plant families Coniferae and Berberidaceae (e.g. species of Juniperus and Podophyllum). Podofilox 0.5% solution is indicated for the topical treatment of external genital warts (Condyloma acuminatum). This product is not indicated in the treatment of perianal or mucous membrane warts. Treatment of genital warts with podofilox results in necrosis of visible wart tissue. The exact mechanism of action is unknown, but is believed to exert its antimitotic effect by binding to tubulin, at a site close to but not identical to the binding site of colchicine; it is thought that this antimitotic effect causes necrosis of wart tissue, the observed clinical effect. In addition, podofilox is known to interfere with nucleoside transport, which may also contribute to its action. Adverse effects reported in less than 5% of the patients included pain with intercourse, insomnia, tingling, bleeding, tenderness, chafing, malodor, dizziness, scarring, vesicle formation, crusting edema, dryness/peeling, foreskin irretraction, hematuria, vomiting and ulceration.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin 30 Target ID: CHEMBL2095182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2011590	Inhibitor 3315

Conditions

Condition	Modality	Targets	Highest Phase	Product
External genital warts (Condyloma acuminatum) 1 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=affc1058-7355-4486-8b65-378fea6f9454	Primary		Approved 4033	CONDYLOX Approved Use Podofilox Topical Solution 0.5% is indicated for the topical treatment of external genital warts (Condyloma acuminatum). This product is not indicated in the treatment of perianal or mucous membrane warts (see PRECAUTIONS ). Diagnosis Although genital warts have a characteristic appearance, histopathologic confirmation should be obtained if there is any doubt of the diagnosis. Differentiating warts from squamous cell carcinoma (so-called Bowenoid papulosis) is of particular concern. Squamous cell carcinoma may also be associated with human papillomavirus but should not be treated with Podofilox Topical Solution 0.5%. Launch Date 6.6104643E11

C_max

Value	Dose	Co-administered	Analyte	Population
17 ng/mL DRUG LABEL https://www.drugs.com/pro/podofilox.html	1.5 mL single, topical dose: 1.5 mL route of administration: Topical experiment type: SINGLE co-administered:		PODOFILOX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.5 h DRUG LABEL https://www.drugs.com/pro/podofilox.html	1.5 mL single, topical dose: 1.5 mL route of administration: Topical experiment type: SINGLE co-administered:		PODOFILOX plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.5 % 2 times / day multiple, topical Recommended Dose: 0.5 %, 2 times / day Route: topical Route: multiple Dose: 0.5 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/	unhealthy, adult n = 26 Health Status: unhealthy Condition: Perianal warts Age Group: adult Sex: F Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/	Other AEs: Inflammation, Pain... Other AEs: Inflammation (79.2%) Pain (79.2%) Itching (83.3%) Bleeding (45.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/
0.5 % 2 times / day multiple, topical Recommended Dose: 0.5 %, 2 times / day Route: topical Route: multiple Dose: 0.5 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/	unhealthy, adult n = 82 Health Status: unhealthy Condition: External genital warts Age Group: adult Sex: F Population Size: 82 Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/	Other AEs: Inflammation, Pain... Other AEs: Inflammation (49.4%) Pain (54.3%) Itching (59.3%) Bleeding (29.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/
0.5 % 2 times / day multiple, topical Recommended Dose: 0.5 %, 2 times / day Route: topical Route: multiple Dose: 0.5 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/	unhealthy, adult n = 86 Health Status: unhealthy Condition: Anogenital warts Age Group: adult Sex: F Population Size: 86 Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/	Other AEs: Inflammation, Pain... Other AEs: Inflammation (52.3%) Pain (55.8%) Itching (60.5%) Bleeding (32.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/
0.5 % 2 times / day multiple, topical Recommended Dose: 0.5 %, 2 times / day Route: topical Route: multiple Dose: 0.5 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/	unhealthy, adult n = 119 Health Status: unhealthy Condition: External genital warts Age Group: adult Sex: M Population Size: 119 Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/	Other AEs: Inflammation, Pain... Other AEs: Inflammation (83.2%) Pain (49.6%) Itching (52.9%) Bleeding (28.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/
0.5 % 2 times / day multiple, topical Recommended Dose: 0.5 %, 2 times / day Route: topical Route: multiple Dose: 0.5 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/	unhealthy, adult n = 127 Health Status: unhealthy Condition: Anogenital warts Age Group: adult Sex: M Population Size: 127 Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/	Other AEs: Inflammation, Pain... Other AEs: Inflammation (81.9%) Pain (50.4%) Itching (52.8%) Bleeding (26.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/
0.5 % 2 times / day multiple, topical Recommended Dose: 0.5 %, 2 times / day Route: topical Route: multiple Dose: 0.5 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/	unhealthy, adult n = 14 Health Status: unhealthy Condition: Perianal warts Age Group: adult Sex: M Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/	Other AEs: Inflammation, Pain... Other AEs: Inflammation (71.4%) Pain (71.4%) Itching (57.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/9449907/
0.5 % 2 times / day multiple, topical Recommended Dose: 0.5 %, 2 times / day Route: topical Route: multiple Dose: 0.5 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1997/020529s000lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: Anogenital warts Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1997/020529s000lbl.pdf	Other AEs: Inflammation, Pain... Other AEs: Inflammation (mild, 32.2%) Pain (mild, 23.7%) Itching (mild, 32.2%) Bleeding (mild, 19.2%) Inflammation (moderate, 30.4%) Pain (moderate, 20.4%) Itching (moderate, 16%) Bleeding (moderate, 3%) Inflammation (severe, 9.3%) Pain (severe, 11.5%) Itching (severe, 7.8%) Bleeding (severe, 0.7%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1997/020529s000lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 753	inhibitor 825	inhibitor 894

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A1 90 CYP2C8 417 CYP2E1 424 CYP2A6 334

Drug as perpetrator

Target	Modality	Activity
CYP2A6 356	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/22116286/	no
CYP2C8 448	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/22116286/	no
CYP2D6 908	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/22116286/	no
CYP2E1 467	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/22116286/	no
CYP3A4 920	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/27336918/ \| https://pubmed.ncbi.nlm.nih.gov/22116286/	yes [IC50 1.1 uM]
CYP2C9 851	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/22116286/	yes [IC50 4.6 uM]
MRP1 87	supressor 73 Sources: https://pubmed.ncbi.nlm.nih.gov/29678463/	yes
P-gp 754	supressor 73 Sources: https://pubmed.ncbi.nlm.nih.gov/29678463/	yes
UGT1A1 117	inhibitor 1612 Sources: https://pubmed.ncbi.nlm.nih.gov/26012253/	yes

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-0462	http://www.3bsc.com/index/pro_info.php?id=19818
3B Scientific (Wuhan) Corp	3B1-00688	http://www.3bsc.com/index/pro_info.php?id=20900
AA Blocks	AA003A9R	https://www.aablocks.com/goods/Goods/detail?id=AA003A9R
AHH Chemical co.,ltd	API-1441	http://www.ahhchemical.com/product/API-1441.html
AHH Chemical co.,ltd	MT-58075	http://www.ahhchemical.com/product/MT-58075.html
AHH Chemical co.,ltd	NP-0421	http://www.ahhchemical.com/product/NP-0421.html
AK Scientific, Inc. (AKSCI)	70719	http://www.aksci.com/item_detail.php?cat=70719
Aaron Chemicals	AR003B1J	http://www.aaronchem.com/518-28-5
AbMole Bioscience	M3496	http://www.abmole.com/products/podophyllotoxin.html
Achemtek	0104-003876	http://www.achemtek.com/518-28-5
Acorn PharmaTech	ACN-035836	http://www.acornpharmatech.com/
Acros Organics	AC228411000	https://www.fishersci.com/shop/products/podophyllotoxin-95-acros-organics-1/AC228411000
Acros Organics	AC228410010	https://www.fishersci.com/shop/products/podophyllotoxin-95-acros-organics/AC228410010
Alfa Chemistry	125670-69-1	https://www.alfa-chemistry.com/cas_125670-69-1.htm
Alinda	ALBB-020906	http://alinda.ru/finechem_en_.html?i=ALBB-020906
Aurum Pharmatech LLC	W-5067	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5067
AvaChem Scientific	2680	http://www.avachem.com/productSearch.asp?2680
Axon MedChem	3368	https://www.axonmedchem.com/product/3368
BLD Pharm	BD41750	http://www.bldpharm.com/products/518-28-5.html
BioChemPartner	BCP24085	http://www.biochempartner.com/518-28-5-BCP24085
BioSynth	P-6980	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/P-6980.html
Boerchem	BC202956	http://www.boerchem.com/?product_34100.html
CSNpharm	CSN16748	https://www.csnpharm.com/products/podophyllotoxin.html
Capot Chemical	20017	http://www.capotchem.com/en/20017.htm
Capot Chemical	PubChem20017	http://www.capotchem.com/en/20017.htm
Chem Scene	CS-1185	http://www.chemscene.com/518-28-5.html
ChemFaces	CFN99168	http://www.chemfaces.com/natural/Podophyllotoxin-CFN99168.html
ChemMol	30101274	http://www.chemmol.com/chemmol/30101274.html
ChemMol	44001388	http://www.chemmol.com/chemmol/44001388.html
ChemMol	99098085	http://www.chemmol.com/chemmol/99098085.html
Chemenu	CM110307	http://www.chemenu.com/products/CM110307
Chemspace	CSSB00000743982	https://chem-space.com/CSSB00000743982
Clearsynth	CS-O-30735	https://www.clearsynth.com/en/CSO30735.html
DAOGE BIOPHARMA	DG21-11821	https://www.daogechem.com/product/518-28-5.html
DC Chemicals	DCG-007	http://www.dcchemicals.com//product_show-Podophyllotoxin.html
Glentham Life Sciences	GE0412	http://www.glentham.com/products/product/GE0412/
Hairui	HR138842	http://www.hairuichem.com/en/product/518-28-5.html
Herbest Bio-Tech	HP200546	http://www.bjherbest.com/analytical-standard/lignans/podophyllotoxin-518-28-5.html
Lab Network	LN00178261	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00178261
Matrix Scientific	79670	https://www.matrixscientific.com/079670.html
MedChem Express	HY-15552	https://www.medchemexpress.com/Podophyllotoxin.html
MuseChem	I003874	https://www.musechem.com/product/I003874.html
OChem	12425	http://www.ocheminc.com/index.php?act=psearch&pid=518P285
Oakwood	358381	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=162982&ExtHyperLink=1
Otava	12486930	https://search.otavachemicals.com/#!/search?query=12486930&type=code&base=dbb
Parchem	36299	http://www.parchem.com/chemical-supplier-distributor/podophyllotoxin-026299.aspx
R&D Chemicals	8646	http://www.rdchemicals.com/chemicals.php?mode=details&mol_id=8165
Renno Tech	RL03911	http://www.rennotech.com/product_show.asp?id=4231
Sigma-Aldrich	858447_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/858447?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	73379_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/73379?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	P4405_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/p4405?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
TripleBond	CP0089	http://www.triplebond-canada.com/prod/1520/
VladaChem	VL262072-100MG	https://www.vladachem.com/product.php?products=518-28-5
Yuhao Chemical	JZ2488	http://www.chemyuhao.com/4354-76-1.html
abcr GmbH	AB167899	http://www.abcr.com/shop/en/AB167899
eNovation Chemicals	D512514	https://www.enovationchem.com/ProductDetails.asp?ProductID=D512514
iChemical	EBD2184800	http://www.ichemical.com/products/518-28-5.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
mcule	MCULE-9617461427	https://mcule.com/MCULE-9617461427/

PubMed

Title	Date	PubMed
Sensory neuropathy due to Bajiaolian (Podophyllotoxin) intoxication.	2000	10965167
TEL/AML1 gene fusion is related to in vitro drug sensitivity for L-asparaginase in childhood acute lymphoblastic leukemia.	2000 Aug 1	10910927
Enhanced podophyllotoxin production from Agrobacterium rhizogenes transformed cultures of Podophyllum hexandrum.	2001	11833617
Issues and practicalities of treating genital warts in the community. Proceedings of a round table meeting facilitated by Succinct Communications Limited.	2001	11333177
Long-term follow-up in patients treated with Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease.	2001 Apr	11328296
A phase I study in paediatric patients to evaluate the safety and pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin.	2001 Apr 20	11308249
Secoisolariciresinol dehydrogenase purification, cloning, and functional expression. Implications for human health protection.	2001 Apr 20	11278426
The successful treatment of molluscum contagiosum with podophyllotoxin (0.5%) self-application.	2001 Dec	11791521
A fast and simple GC MS method for lignan profiling in Anthriscus sylvestris and biosynthetically related Plant species.	2001 Dec	11745025
Podophyllin office therapy against condyloma should be abandoned.	2001 Dec	11714936
High yield of podophyllotoxin from leaves of Podophyllum peltatum by in situ conversion of podophyllotoxin 4- O-beta-D-glucopyranoside.	2001 Feb	11270736
[Clinical aspects and therapy of anogenital warts and papillomavirus-associated lesions].	2001 Jan	11220242
GATA-4 and serum response factor regulate transcription of the muscle-specific carnitine palmitoyltransferase I beta in rat heart.	2001 Jan 12	11038368
Cytotoxic responses to aromatic ring and configurational variations in alpha-conidendrin, podophyllotoxin, and sikkimotoxin derivatives.	2001 Jan 18	11170627
[PAPP-A in the first trimester of pregnancy].	2001 Jul	11569426
TNF-alpha downregulates murine hepatic growth hormone receptor expression by inhibiting Sp1 and Sp3 binding.	2001 Jun	11390427
The production of cytotoxic lignans by plant cell cultures.	2001 Mar	11330705
Direct medical costs for surgical and medical treatment of condylomata acuminata.	2001 Mar	11255335
Contact dermatitis from topical antiviral drugs.	2001 May	11298689
A pancreatic beta -cell-specific enhancer in the human PDX-1 gene is regulated by hepatocyte nuclear factor 3beta (HNF-3beta ), HNF-1alpha, and SPs transcription factors.	2001 May 18	11278466
Analytical approaches for traditional chinese medicines exhibiting antineoplastic activity.	2001 Nov 25	11817032
Management of anogenital warts (condylomata acuminata).	2001 Nov-Dec	11701422
Second malignancy after treatment of childhood non-Hodgkin lymphoma.	2001 Oct 1	11745271
[Myelotoxicity of a plant cytostatic preparation etoposide].	2001 Sep-Oct	11764496
Treatment of anogenital warts in children with topical 0.05% podofilox gel and 5% imiquimod cream.	2001 Sep-Oct	11737696
Identification of a novel variant of the human NR2B gene promoter region and its possible association with schizophrenia.	2002	12476325
Clinical inquiries. What is the most effective treatment for external genital warts?	2002 Apr	11978251
Antitumor and antioxidant activity of spin labeled derivatives of podophyllotoxin (GP-1) and congeners.	2002 Apr 5	12150207
Biological activity of 4-acetyltropolone, the minor component of Thujopsis dolabrata SIeb. et Zucc. hondai Mak.	2002 Aug	12186430
[Incidence and management of condylomata acuminata by French general physicians].	2002 Aug-Sep	12442095
Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation.	2002 Dec 15	12393626
Prodrugs of 4'-demethyl-4-deoxypodophyllotoxin: synthesis and evaluation of the antitumor activity.	2002 Dec 2	12419378
Human T-cell leukemia virus type I Tax transactivates the matrix metalloproteinase-9 gene: potential role in mediating adult T-cell leukemia invasiveness.	2002 Feb 15	11830485
Differential modulation by estradiol of P-glycoprotein drug resistance protein expression in cultured MCF7 and T47D breast cancer cells.	2002 Jul-Aug	12174911
Flow cytometric estimation on cytotoxic activity of leaf extracts from seashore plants in subtropical Japan: isolation, quantification and cytotoxic action of (-)-deoxypodophyllotoxin.	2002 Jun	12112292
Methamphetamine activates DNA binding of specific redox-responsive transcription factors in mouse brain.	2002 Oct 1	12237866
A multicomponent reaction for the one-pot synthesis of 4-aza-2,3-didehydropodophyllotoxin and derivatives.	2002 Sep 19	12227745
Synthesis and cytotoxicity of podophyllotoxin analogues modified in the A ring.	2003 Jan	12593917
[Bacteremia due to Capnocytophaga spp.: two cases].	2003 Mar	12586027

Patents

Sample Use Guides

In Vivo Use Guide

Apply twice daily morning and evening (every 12 hours), for 3 consecutive days, then withhold use for 4 consecutive days. This 1 week cycle of treatment may be repeated up to four times until there is no visible wart tissue. Podofilox 0.5% solution is applied to the warts with a cotton-tipped applicator supplied with the drug. The drug-dampened applicator should be touched to the wart to be treated, applying the minimum amount of solution necessary to cover the lesion. Treatment should be limited to less than 10 cm2 of wart tissue and to no more than 0.5 mL of the solution per day.

Route of Administration: Vaginal

In Vitro Use Guide

Unknown

Name

Type

Language

PODOFILOX

Official Name

English

PODOPHYLLOTOXIN [EP MONOGRAPH]

Common Name

English

NSC-24818

Code

English

PODOFILOX [VANDF]

Common Name

English

PODOPHYLLOTOXIN

Common Name

English

PODOFILOX [ORANGE BOOK]

Common Name

English

PODOPHYLLOTOXIN [MI]

Common Name

English

PODOPHYLLOTOXIN [WHO-DD]

Common Name

English

PODOPHYLLOTOXIN [MART.]

Common Name

English

CONDYLOX

Brand Name

English

PODOFILOX [HSDB]

Common Name

English

FURO(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.BETA.,8A.ALPHA.,9.ALPHA.))-

Common Name

English

(5R,5AR,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

Common Name

English

PODOFILOX [USAN]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000008732