OMTRIPTOLIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H28O9
Molecular Weight	460.4737
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12C[C@@]3([H])C4=C(CC[C@]3(C)[C@]56O[C@@]5([H])[C@]7([H])O[C@]7(C(C)C)[C@@H](OC(=O)CCC(O)=O)[C@]16O2)C(=O)OC4

InChI

InChIKey=HROMYAWHLUOUPY-AHCCQAQQSA-N

InChI=1S/C24H28O9/c1-10(2)22-17(32-22)18-24(33-18)21(3)7-6-11-12(9-29-19(11)28)13(21)8-14-23(24,31-14)20(22)30-16(27)5-4-15(25)26/h10,13-14,17-18,20H,4-9H2,1-3H3,(H,25,26)/t13-,14-,17-,18-,20+,21-,22-,23+,24+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C24H28O9
Molecular Weight	460.4737
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	9 / 9
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://clinicaltrials.gov/ct2/show/NCT03117920 | https://clinicaltrials.gov/ct2/show/NCT01927965 | https://clinicaltrials.gov/ct2/show/NCT03760523 https://www.ncbi.nlm.nih.gov/pubmed/31109340 | https://www.ncbi.nlm.nih.gov/pubmed/28543919https://www.ncbi.nlm.nih.gov/pubmed/30599444 | https://adisinsight.springer.com/drugs/800016015 | https://www.ncbi.nlm.nih.gov/pubmed/19251409/ | https://www.ncbi.nlm.nih.gov/pubmed/21255694https://www.ncbi.nlm.nih.gov/pubmed/27222828 | https://www.ncbi.nlm.nih.gov/pubmed/25400429
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27921038 https://www.drugs.com/npp/thunder-god-vine.html

Triptolide, the active component of Tripterygium wilfordii Hook F has been used to treat autoimmune and inflammatory conditions for over two hundred years in traditional Chinese medicine. Triptolide possesses immunosuppressive, anti-inflammatory, and anti-cancer effects. Triptolide is a woody vine which is widely distributed in Eastern and Southern China. In China, triptolide is frequently used to treat autoimmune and/or inflammatory diseases due to its favorable cost–benefit ratio. Commercial preparations of triptolide have been commonly used for the treatment of inflammatory and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, nephritis and psoriasis.Triptolide has been demonstrated to exert novel chondroprotective and anti-inflammatory effects on rheumatoid arthritis. Triptolide has been used to treat ADPKD patients in clinical trials in China. Triptolide significantly protected glomerular filtration rate (eGFR) of ADPKD patients compared with placebo. Two recent small clinical studies have demonstrated tiptolide’s effectiveness against rheumatoid arthritis. A larger study confirmed the therapeutic effects of triptolide in the aforementioned studies. Triptolide is among the most powerful and broadly active antiinflammatory/immunomodulating natural products ever discovered. Triptolide acts at nanomolar concentrations and inhibits the production of various cellular targets including inflammatory cytokines, cyclooxygenase, inducible nitric oxide synthase and metalloproteinases and transcription factors. The anti-tumor activity of Triptolide in vitro and in various tumor-bearing animal models has been investigated for years, and many findings showed that Triptolide is a promising agent in anti-tumor therapy. Triptolide has been approved for Phase I clinical trials for the treatment of prostate cancer, but the anti-tumor effect and mechanism of TPL need to be further elucidated.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cytochrome P450 1A2 72 Target ID: CHEMBL3356 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26874845	Inhibitor 8297	14.18 µM [IC50]
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26874845	Inhibitor 8297	8.36 µM [IC50]
NF-kappa B signaling pathway 84 Target ID: map04064 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26531258	Inhibitor 8297
HuCCT1, human cholangiocarcinoma 5 Target ID: HuCCT1, human cholangiocarcinoma Sources: https://www.ncbi.nlm.nih.gov/pubmed/24742042	Inhibitor 8297	12.6 nM [IC50]
beta-amyloid formation 6 Target ID: GO:0034205 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23126204	Inhibitor 8297	30.0 pM [IC50]
Proteinase-activated receptor 2 7 Target ID: CHEMBL5963 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23895492	Antagonist 2778	14.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Autosomal dominant polycystic kidney disease 7 Sources: https://clinicaltrials.gov/ct2/show/NCT02115659	Primary	Phase III 656	Unknown Approved Use Unknown
HIV-1 infection 151 Sources: https://clinicaltrials.gov/ct2/show/NCT01817283 https://clinicaltrials.gov/ct2/show/NCT02219672	Primary	Phase III 656	Unknown Approved Use Unknown
Crohn's disease 42 Sources: https://clinicaltrials.gov/ct2/show/NCT02044952	Primary	Phase III 656	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 substrate 1737	substrate 1037 inhibitor 1767	inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 BCRP 699 CYP2C8 911 CYP1A2 1524 P-gp 1461 CYP2A6 707 CYP2E1 882	CYP2C8 693 CYP2E1 667 CYP1A2 1054 CYP2A6 543 P-gp 1537 CYP2C19 991 CYP2B6 664 OCT2 355

Drug as perpetrator

Target	Modality	Activity
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26874845/	no [Inhibition 100 uM]
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26874845/	no [Inhibition 100 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26874845/	no [Inhibition 100 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26874845/	no [Inhibition 100 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26874845/	no [Inhibition 100 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26874845/	no [Inhibition 50 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26874845/	no [Inhibition 50 uM]
BCRP 773	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1325#sid=26719814	no
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26874845/	yes [IC50 14.18 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26874845/	yes [IC50 8.36 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18982531/	no
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18982531/	no
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18982531/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18982531/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18982531/	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18982531/	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18982531/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18982531/	yes
OCT2 355	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31644961/	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30112986/	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30112986/	yes	yes (co-administration study) Comment: Grapefruit juice increased AUC and Cmax by 153% and 141% Sources: https://pubmed.ncbi.nlm.nih.gov/30112986/

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0036BN	https://www.1pchem.com/search?query=1P0036BN
A2B Chem	AB47363	http://a2bchem.com/prod/AB47363
AChemBlock	10401	http://www.achemblock.com/catalogsearch/result/?q=10401
AK Scientific	S493	https://aksci.com/item_detail.php?cat=S493
Ambeed	A550309	http://www.ambeed.com/search/Search.html?keyword=A550309
ApexBio Technology	A3891	https://www.apexbt.com/catalogsearch/result/?q=A3891
AstaTech	44358	http://astatechinc.com/CPSResult.php?CRNO=44358
BLD Pharm	BD9097	http://www.bldpharm.com/search/Search.html?keyword=BD9097
BOC Sciences	38748-32-2	http://www.bocsci.com/description.asp?cas=38748-32-2
BioSynth	Q-100450	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/Q-100450
Biopurify Phytochemicals	BP1411	https://www.phytopurify.com/search.do?a=s&searchtype=3&psize=10&q=BP1411&searchhtmp=simplesearch&t=1
Cayman Chemical	11973	http://www.caymanchem.com/app/template/Product.vm/catalog/11973
Chem Scene	CS-0286	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0286
Chem-Impex International	30404	http://www.chemimpex.com/category/search/30404/2?filter=&search=30404&type=q&keywordoption=ANY&cid=2&fltrdesc=
ChemShuttle	151843	https://www.chemshuttle.com/catalogsearch/result/?q=151843
Chemodex	T0237	http://www.chemodex.com/products/T0237
Lab Network	LN01293795	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01293795
Lab Network	LN02196201	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN02196201
Lab Seeker	SC-14019	http://www.labseeker.com/search.php?keywords=SC-14019&category=0
LabSeeker	SC-14019	http://www.labseeker.com/search.php?keywords=SC-14019&category=0
MedChem Express	HY-32735	https://www.medchemexpress.com/search.html?q=HY-32735&ft=&fa=&fp=
MolPort	MolPort-016-638-463	https://www.molport.com/shop/molecule-link/MolPort-016-638-463
Molnova	M14333	https://www.molnova.com/en/serch-list.html?keywords=M14333
PI Chemicals	PI-28474	http://www.pipharm.com/catalog_products/PI-28474.html
Ryan Scientific	Cyclopamine	https://ryansci.com/products?q=Cyclopamine&list_q=&search_type=exact
Selleck Chemicals	S3604	http://www.selleckchem.com/search.html?searchDTO.searchParam=S3604
ShangHai Biochempartner	BCP000185	http://www.biochempartner.com/search_BCP000185
TargetMol	T2179	https://www.targetmol.com/search?keyword=T2179
Tetrahedron	TS59472	http://www.thsci.com/search.do?q=TS59472
Tocris	3253	https://www.tocris.com/search.php?Type=QuickSearch&Value=3253
Toronto Research Chemicals	T815600	https://www.trc-canada.com/product-detail/?CatNum=T815600
W&J PharmaChem	50C186866	http://wjpharmachem.com/new/searcht.php?keyword=50C186866
eMolecules	25686240	https://orderbb.emolecules.com/search/#?query=25686240
eMolecules	29781300	https://orderbb.emolecules.com/search/#?query=29781300
eMolecules	300613932	https://orderbb.emolecules.com/search/#?query=300613932
eNovation Chemicals	D480547	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D480547&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-3581898493	https://mcule.com/MCULE-3581898493/
mcule	MCULE-5702185362	https://mcule.com/MCULE-5702185362/

PubMed

Title	Date	PubMed
PG490-88, a derivative of triptolide, blocks bleomycin-induced lung fibrosis.	2001 Mar	11238047
Mechanisms of tolerance induced by PG490-88 in a bone marrow transplantation model.	2002 Jan 15	11792990
Triptolide suppresses CD80 and CD86 expressions and IL-12 production in THP-1 cells.	2005 Feb	15663903
[Study of triptolide-induced apoptosis in MUTZ-1 cells and its allied mechanism].	2005 Jun	15972136
Dipyridamole activation of mitogen-activated protein kinase phosphatase-1 mediates inhibition of lipopolysaccharide-induced cyclooxygenase-2 expression in RAW 264.7 cells.	2006 Jul 17	16765938
Triptolide binds covalently to a 90 kDa nuclear protein. Role of epoxides in binding and activity.	2007	17678712
Triptolide upregulates NGF synthesis in rat astrocyte cultures.	2007 Jul	17401680
Differential expression and oxidation of MKP-1 modulates TNF-alpha gene expression.	2007 Sep	17507666
Triptolide cooperates with chemotherapy to induce apoptosis in acute myeloid leukemia cells.	2008 Dec	18922616
Upregulation of ICAM-1 expression in bronchial epithelial cells by airway secretions in bronchiectasis.	2008 Feb	17931847
Triptolide protects podocytes from puromycin aminonucleoside induced injury in vivo and in vitro.	2008 Sep	18509322
Phase I dose-escalation study of F60008, a novel apoptosis inducer, in patients with advanced solid tumours.	2009 Jul	19251409
Caspase 3 is involved in the apoptosis induced by triptolide in HK-2 cells.	2009 Jun	19233258
Interleukin-6-independent expression of glucocorticoid receptor is upregulated by triptolide in multiple myeloma.	2009 May	19330649
Heat shock protein 72 protects kidney proximal tubule cells from injury induced by triptolide by means of activation of the MEK/ERK pathway.	2009 May-Jun	19546256
Sex differences in subacute toxicity and hepatic microsomal metabolism of triptolide in rats.	2010 Apr 30	20223271
Effects of cytochrome P4503A inducer dexamethasone on the metabolism and toxicity of triptolide in rat.	2010 Feb 1	19879934
Triptolide alters histone H3K9 and H3K27 methylation state and induces G0/G1 arrest and caspase-dependent apoptosis in multiple myeloma in vitro.	2010 Jan 12	19879315
Identification of triptolide, a natural diterpenoid compound, as an inhibitor of lung inflammation.	2010 Jun	20348278
Physio-pathological parameters affect the activation of inflammatory pathways by deoxynivalenol in Caco-2 cells.	2010 Oct	20633634
Knockout of hepatic P450 reductase aggravates triptolide-induced toxicity.	2011 Aug 10	21596114
Cytotoxicity of Triptolide and Triptolide loaded polymeric micelles in vitro.	2011 Dec	21640813
Effect of triptolide on progesterone production from cultured rat granulosa cells.	2012 Jun	22592319
Triptolide down-regulates COX-2 expression and PGE2 release by suppressing the activity of NF-κB and MAP kinases in lipopolysaccharide-treated PC12 cells.	2012 Mar	21717513
Role of Nrf2 in protection against triptolide-induced toxicity in rat kidney cells.	2012 Sep 3	22820427
Minnelide: a novel therapeutic that promotes apoptosis in non-small cell lung carcinoma in vivo.	2013	24143232
Gene expression profiling and pathway analysis of hepatotoxicity induced by triptolide in Wistar rats.	2013 Aug	23639586
Establishment of hypoxia induction in an in vivo animal replacement model for experimental evaluation of pancreatic cancer.	2014 Jul	24842335
Triptolide-induced oxidative stress involved with Nrf2 contribute to cardiomyocyte apoptosis through mitochondrial dependent pathways.	2014 Nov 4	25169008
Interleukin-17 mediates triptolide-induced liver injury in mice.	2014 Sep	24949944
Inhibition of P-glycoprotein Gene Expression and Function Enhances Triptolide-induced Hepatotoxicity in Mice.	2015 Jul 2	26134275
Triptolide disrupts fatty acids and peroxisome proliferator-activated receptor (PPAR) levels in male mice testes followed by testicular injury: A GC-MS based metabolomics study.	2015 Oct 2	26219505
Protection of Quercetin against Triptolide-induced apoptosis by suppressing oxidative stress in rat Leydig cells.	2015 Oct 5	26277538
Suppression of the migration and invasion is mediated by triptolide in B16F10 mouse melanoma cells through the NF-kappaB-dependent pathway.	2016 Dec	26420756
Downregulation of Sp1 by Minnelide leads to decrease in HSP70 and decrease in tumor burden of gastric cancer.	2017	28192510
PG490-88, a derivative of triptolide, suppresses ischemia/reperfusion-induced lung damage by maintaining tight junction barriers and targeting multiple signaling pathways.	2019 Mar	30599444
Pre-clinical evaluation of Minnelide as a therapy for acute myeloid leukemia.	2019 May 20	31109340

Patents

Sample Use Guides

In Vivo Use Guide

Minnelide will be administered at the dose of 0.67 mg/m2 as a 30 min infusion intravenously daily on days 1-21 of each cycle followed by a 7 day rest period (days 22-28)

Route of Administration: Intravenous

In Vitro Use Guide

The A549/Taxol cells were treated with different concentrations of Triptolide (0.03, 0.3 or 3 uM/l) for 2, 4, 6 and 12 h. On exposure to 3 uM Triptolide for 2, 4, 6 and 12 h, the extent of cell apoptosis observed markedly increased. The inhibitory effect reached a maximum with 3 uM Triptolide at the 12 h time point (cell apoptotic rate, 65.33%), whereas the apoptotic rate of the control group was 7.23% at 12 h.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:25:28 GMT 2023` Edited by `admin` on `Fri Dec 15 16:25:28 GMT 2023`
Record UNII	D36ELM729P
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

OMTRIPTOLIDE

Official Name

English

4-(((3BS,4AS,5AR,6R,6AS,7AS,7BS,8AS,8BS)-6A-ISOPROPYL-8B-METHYL-1-OXO-1,3,3B,4,4A,6,6A,7A,7B,8B,9,10-DODECAHYDROTRISOXIRENO(6,7:8A,9:4B,5)PHENANTHRO(1,2-C)FURAN-6-YL)OXY)-4-OXOBUTANOIC ACID

Common Name

English

Omtriptolide [WHO-DD]

Common Name

English

omtriptolide [INN]

Common Name

English

PG-490-88

Code

English

BUTANEDIOIC ACID, MONO((3BS,4AS,5AR,6R,6AS,7AS,7BS,8AS,8BS)-1,3,3B,4,4A,6,6A,7A,7B,8B,9,10-DODECAHYDRO-8B-METHYL-6A-(1-METHYLETHYL)-1-OXOTRISOXIRENO(6,7:8A,9:4B,5)PHENANTHRO(1,2-C)FURAN-6-YL) ESTER

Common Name

English

PG490-88

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C574