TRIPARANOL

US Previously Marketed

First approved in 1960

Details

Stereochemistry	RACEMIC
Molecular Formula	C27H32ClNO2
Molecular Weight	438.001
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN(CC)CCOC1=CC=C(C=C1)C(O)(CC2=CC=C(Cl)C=C2)C3=CC=C(C)C=C3

InChI

InChIKey=SYHDSBBKRLVLFF-UHFFFAOYSA-N

InChI=1S/C27H32ClNO2/c1-4-29(5-2)18-19-31-26-16-12-24(13-17-26)27(30,23-10-6-21(3)7-11-23)20-22-8-14-25(28)15-9-22/h6-17,30H,4-5,18-20H2,1-3H3

HIDE SMILES / InChI

Molecular Formula	C27H32ClNO2
Molecular Weight	438.001
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/13852511
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26305256 | https://www.ncbi.nlm.nih.gov/pubmed/22877755 | https://www.ncbi.nlm.nih.gov/pubmed/13852510 |

Triparanol (brand and developmental code names MER/29) is a 24-dehydro cholesterol reductase inhibitor, which is an enzyme involved in the biosynthesis of cholesterol. It has antitumor properties, such as decreasing proliferation and inducing apoptosis in many cancer cell lines and slowing tumor growth in a mouse xenograft model. It can also decrease Hedgehog pathway signaling in cancer cells. Triparanol was the first synthetic cholesterol-lowering drug. It was withdrawn in 1962 due to severe adverse effects such as nausea and vomiting, vision loss due to irreversible cataracts, alopecia, skin disorders (e.g., dryness, itching, peeling, and "fish-scale" texture), and accelerated atherosclerosis and is now considered to be obsolete.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Delta(24)-sterol reductase 4 Target ID: CHEMBL2331059 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26789657	Inhibitor 8297
3-beta-hydroxysteroid-delta(8),delta(7)-isomerase 7 Target ID: CHEMBL4931 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16033255	Inhibitor 8297		11.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Coronary artery disease 48 Sources: https://www.ncbi.nlm.nih.gov/pubmed/13852510	Primary		Approved 8429	MER-29 Approved Use Unknown
Hypercholesterolemia 47 Sources: https://www.ncbi.nlm.nih.gov/pubmed/13662262	Primary		Approved 8429	MER-29 Approved Use Unknown

Doses

Dose	Population	Adverse events
1500 mg 1 times / day multiple, oral Highest studied dose Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4230196	unhealthy, 23 years n = 1 Health Status: unhealthy Age Group: 23 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/4230196	Disc. AE: Cataracts... AEs leading to discontinuation/dose reduction: Cataracts (severe, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/4230196
250 mg 1 times / day multiple, oral (starting) Recommended Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14451692	unhealthy, 42-66 years n = 15 Health Status: unhealthy Age Group: 42-66 years Sex: M+F Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/14451692	Disc. AE: Angina pectoris... AEs leading to discontinuation/dose reduction: Angina pectoris (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/14451692
250 mg 1 times / day multiple, oral Recommended Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4230196	unhealthy, 6-59 years n = 8 Health Status: unhealthy Age Group: 6-59 years Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/4230196	Disc. AE: Cataracts... AEs leading to discontinuation/dose reduction: Cataracts (severe, 8 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/4230196
250 mg 1 times / day multiple, oral Recommended Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5846503	unhealthy, 70 years n = 1 Health Status: unhealthy Age Group: 70 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5846503	Disc. AE: Malabsorption syndrome, Mucosal atrophy... AEs leading to discontinuation/dose reduction: Malabsorption syndrome (1 patient) Mucosal atrophy (severe, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/5846503

AEs

AE	Significance	Dose	Population
Cataracts	severe, 1 patient Disc. AE	1500 mg 1 times / day multiple, oral Highest studied dose Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4230196	unhealthy, 23 years n = 1 Health Status: unhealthy Age Group: 23 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/4230196
Angina pectoris	2 patients Disc. AE	250 mg 1 times / day multiple, oral (starting) Recommended Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14451692	unhealthy, 42-66 years n = 15 Health Status: unhealthy Age Group: 42-66 years Sex: M+F Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/14451692
Cataracts	severe, 8 patients Disc. AE	250 mg 1 times / day multiple, oral Recommended Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4230196	unhealthy, 6-59 years n = 8 Health Status: unhealthy Age Group: 6-59 years Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/4230196
Malabsorption syndrome	1 patient Disc. AE	250 mg 1 times / day multiple, oral Recommended Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5846503	unhealthy, 70 years n = 1 Health Status: unhealthy Age Group: 70 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5846503
Mucosal atrophy	severe, 1 patient Disc. AE	250 mg 1 times / day multiple, oral Recommended Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5846503	unhealthy, 70 years n = 1 Health Status: unhealthy Age Group: 70 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5846503

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://link.springer.com/article/10.1007/s13721-020-00229-8 Page: 8.0

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY571702	https://www.001chemical.com/chem/78-41-1
3B Scientific (Wuhan) Corp	3B3-032302	http://www.3bsc.com/index/pro_info.php?id=53566
AA Blocks	AA0053GV	https://www.aablocks.com/goods/Goods/detail?id=AA0053GV
AHH Chemical co.,ltd	MT-25371	http://www.ahhchemical.com/product/MT-25371.html
Alfa Chemistry	AP78411	https://reagents.alfa-chemistry.com/product/triparanol-cas-78-41-1-16567.html
Ambinter	Amb17621089	http://www.ambinter.com/reference/17621089
Aurora Fine Chemicals LLC	A17.904.204	http://online.aurorafinechemicals.com/info?ID=A17.904.204
Chemspace	CSSB00020665992	https://chem-space.com/CSSB00020665992
Clearsynth	CS-T-62510	https://www.clearsynth.com/en/CST62510.html
DC Chemicals	DC37492	http://www.dcchemicals.com//product_show-Triparanol.html
Finetech	FT-0675655	http://www.finetechnology-ind.com/prod/detail/pub/78-41-1.html
Glentham Life Sciences	GP7426	http://www.glentham.com/products/product/GP7426/
Molcore	MC571702	https://www.molcore.com/product/78-41-1
Sigma-Aldrich	T5200_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/t5200?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S545927	http://www.smolecule.com/products/s545927
THE BioTek	bt-287043	https://www.thebiotek.com/product/inhibitors/bt-287043

PubMed

Title	Date	PubMed
Toxicologic lesions associated with two related inhibitors of oxidosqualene cyclase in the dog and mouse.	2001 Mar-Apr	11421484
Molecular mechanisms underlying limb anomalies associated with cholesterol deficiency during gestation: implications of Hedgehog signaling.	2003 May 15	12719383
Dysregulation of hedgehog signalling predisposes to synovial chondromatosis.	2005 Jun	15834844
Constitutive hedgehog signaling in chondrosarcoma up-regulates tumor cell proliferation.	2006 Jan	16400033
Inhibition of cholesterol biosynthesis disrupts lipid raft/caveolae and affects insulin receptor activation in 3T3-L1 preadipocytes.	2009 Sep	19433058
Age estimation in 25-45 yrs. old females by physical and radiological methods.	2010 Jul	21731347

Patents

Sample Use Guides

In Vivo Use Guide

maximally effective dose of 250 mg. per day

Route of Administration: Oral

In Vitro Use Guide

Lung cancer A549; breast cancer MCF7; hepatocellular carcinoma (liver cancer) HepG2; pancreatic cancer cell line bxpc3; prostate cancer cell line LnCAP; melanoma G361; and normal fibroblast were used for activity evaluation. One day before treatment, cells (5 _ 104) will be plated in 96-wells in growth medium without antibiotics and with reduced serum (2.5%). Cells will be incubated with Triparanol at different concentrations (0.5 and 1 mkM) as indicated with or without cholesterol (5 lM) in the same medium until ready for further analysis. Cells will be treated with Triparanol in 96-well plates for 6–7 days. Cell proliferation was assayed by MTS assay (Promega) according to the manufacturer’s protocol.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:04:54 GMT 2023` Edited by `admin` on `Fri Dec 15 15:04:54 GMT 2023`
Record UNII	63S8C3RXGS
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TRIPARANOL

Official Name

English

triparanol [INN]

Common Name

English

TRIPARANOL [MI]

Common Name

English

Triparanol [WHO-DD]

Common Name

English

NSC-65345

Code

English

2-P-CHLOROPHENYL-1-(P-(2-DIETHYLAMINOETHOXY)PHENYL)-1-P-TOLYLETHANOL

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29703