ANDROGRAPHOLIDE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H30O5
Molecular Weight	350.4492
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12CCC(=C)[C@@H](C\C=C3/[C@H](O)COC3=O)[C@]1(C)CC[C@@H](O)[C@@]2(C)CO

InChI

InChIKey=BOJKULTULYSRAS-OTESTREVSA-N

InChI=1S/C20H30O5/c1-12-4-7-16-19(2,9-8-17(23)20(16,3)11-21)14(12)6-5-13-15(22)10-25-18(13)24/h5,14-17,21-23H,1,4,6-11H2,2-3H3/b13-5+/t14-,15-,16+,17-,19+,20+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27896563
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25553378

Andrographolide, a diterpenoid, is known for its anti-inflammatory effects. It can be isolated from various plants of the genus Andrographis, commonly known as 'creat'. Andrographolide has been tested for its anti-inflammatory effects in various stressful conditions, such as ischemia, pyrogenesis, arthritis, hepatic or neural toxicity, carcinoma, and oxidative stress. Apart from its anti-inflammatory effects, andrographolide also exhibits immunomodulatory effects by effectively enhancing cytotoxic T cells, natural killer (NK) cells, phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). The properties of andrographolide, such as its ability to induce apoptosis of cancer cells and inhibition of DTH, its anti-oxidative and cytoprotective effect, and its ability to enhance CTLs and NK cell activation makes it a potent antiviral agent. Andrographolide inhibited the growth of human breast, prostate, and hepatoma tumors. Andrographolide could be a potent anticancer agent when used in combination with other chemotherapeutic agents.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Nuclear factor NF-kappa-B complex 11 Target ID: CHEMBL2094258 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15356172 \| https://www.ncbi.nlm.nih.gov/pubmed/27793052	Inhibitor 8297
Interleukin-1 alpha 2 Target ID: P01583 Gene ID: 3552.0 Gene Symbol: IL1A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/24799081	Inhibitor 8297	0.34 µM [IC50]
Interleukin-1 beta 22 Target ID: CHEMBL1909490 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24799081	Inhibitor 8297	1.52 µM [IC50]
Interleukin-6 4 Target ID: CHEMBL1795129 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24799081	Inhibitor 8297	0.56 µM [IC50]
MCF7 21 Target ID: CHEMBL387 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25506809	Inhibitor 8297	14.87 µM [IC50]
HCT-116 7 Target ID: CHEMBL394 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25506809	Inhibitor 8297	14.18 µM [IC50]
Hepatitis B virus 8 Target ID: CHEMBL613497 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24731274 \| https://www.ncbi.nlm.nih.gov/pubmed/27896563	Inhibitor 8297	54.1 µM [IC50]
DLD-1 1 Target ID: CHEMBL614285 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24875131	Inhibitor 8297	151.4 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Colorectal cancer 101 Sources: https://clinicaltrials.gov/ct2/show/NCT01993472	Primary		Phase II 1132	Unknown Approved Use Unknown
Multiple sclerosis 104 Sources: https://clinicaltrials.gov/ct2/show/NCT02273635	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
141.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11081986	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		ANDROGRAPHOLIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
1294 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11081986	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		ANDROGRAPHOLIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.94 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11081986	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		ANDROGRAPHOLIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
45% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11081986	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		ANDROGRAPHOLIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 supressor 21	inhibitor 1767	inhibitor 1852 supressor 1	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 UGT2B4 19 CYP3A4/5 278 OAT1 599 CYP2B6 810 UGT1A3 84 UGT1A8 36 UGT1A6 108 UGT1A10 32 CYP2C 19 UGT2B7 146 UGT1A4 77 UGT1A9 116 UGT1A7 21 CYP2E1 882 UGT1A1 204 OATP1B1 788 OATP1B3 706	UGT1A8 283 UGT2B4 249 UGT2B17 213 P-gp 1537 UGT1A3 422 UGT1A6 307 UGT2B7 389 OAT1 326 UGT1A9 380 UGT1A4 347 UGT2B15 203 UGT1A10 291 UGT1A1 418 UGT1A7 236	OAT1 26

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/21365364/	moderate to weak [IC50 245.7 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18053665/	no [IC50 >100 uM]
CYP2C 34	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18053665/	no [IC50 >100 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/21365364/	no [IC50 >100 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/21365364/	no [IC50 >100 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18053665/	no [IC50 >100 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18053665/	no [IC50 >200 uM]
CYP3A4/5 335	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18053665/	no [IC50 >200 uM]
UGT1A8 48	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24631340/	no [Inhibition 100 uM]
OAT1 603	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/30606060/	no
UGT1A10 41	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24631340/	unlikely [Inhibition 100 uM]
UGT1A4 80	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24631340/	unlikely [Inhibition 100 uM]
UGT2B4 19	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24631340/	unlikely [Inhibition 100 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30606060/	unlikely
UGT1A1 254	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24631340/	weak [Inhibition 100 uM]
UGT1A3 93	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24631340/	weak [Inhibition 100 uM]
UGT1A6 141	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24631340/	weak [Inhibition 100 uM]
UGT1A7 23	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24631340/	weak [Inhibition 100 uM]
UGT1A9 121	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24631340/	weak [Inhibition 100 uM]
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes [Inhibition 10 uM]
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes [Inhibition 10 uM]
UGT2B7 157	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24631340/	yes [Inhibition 100 uM]
CYP1A2 1692	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/21219911/	yes
CYP2D6 1891	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/21219911/	yes
CYP3A4 1925	supressor 155 Sources: https://pubmed.ncbi.nlm.nih.gov/21925256/	yes

Drug as victim

Target	Modality	Activity
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25204783/	major [Km 1.46 uM]
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25204783/	minor [Km 1020 uM]
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25204783/	minor
UGT2B4 249	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25204783/	minor
OAT1 326	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30606060/	no
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25204783/	no
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25204783/	no
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25204783/	no
UGT1A7 236	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25204783/	no
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25204783/	no
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25204783/	no
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25204783/	no
UGT2B15 203	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25204783/	no
UGT2B17 213	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25204783/	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21721007/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/34075974/

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	NO22456	https://www.001chemical.com/chem/search?q=NO22456
1PlusChem LLC	1P003OCV	https://www.1pchem.com/search?query=1P003OCV
A2B Chem	AB70735	http://a2bchem.com/prod/AB70735
AK Scientific	J10022	https://aksci.com/item_detail.php?cat=J10022
AK Scientific	J92516	https://aksci.com/item_detail.php?cat=J92516
AK Scientific	L973	https://aksci.com/item_detail.php?cat=L973
Ambeed	A108018	http://www.ambeed.com/search/Search.html?keyword=A108018
AstaTech	33684	http://astatechinc.com/CPSResult.php?CRNO=33684
BOC Sciences	5508-58-7	http://www.bocsci.com/description.asp?cas=5508-58-7
BioSynth	Q-100624	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/Q-100624
Biopurify Phytochemicals	BP0164	https://www.phytopurify.com/search.do?a=s&searchtype=3&psize=10&q=BP0164&searchhtmp=simplesearch&t=1
Cayman Chemical	11679	http://www.caymanchem.com/app/template/Product.vm/catalog/11679
Chem Scene	CS-3334	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3334
Chem4Pharma	C4PN20	https://www.chem4pharma.com/product-page/C4PN20
ChemDiv	BB01-8144	http://chemistryondemand.com:8080/eShop/search_results.jsp?idnumber=BB01-8144
ChemShuttle	151608	https://www.chemshuttle.com/catalogsearch/result/?q=151608
Combi-Blocks	QA-8068	http://www.combi-blocks.com/cgi-bin/find.cgi?QA-8068
Frontier Scientific Services	501003435	http://orders.frontierssi.com/fssionline32/public/product.aspx?cat=501003435&type=hts
Indofine	A-003	https://indofinechemical.com/details.aspx?Sku=A-003
KeyOrganics	AS-13637	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-13637
KeyOrganics	VS-02751	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=VS-02751
Lab Network	LN01040476	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01040476
Lab Seeker	SC-46922	http://www.labseeker.com/search.php?keywords=SC-46922&category=0
LabSeeker	SC-46922	http://www.labseeker.com/search.php?keywords=SC-46922&category=0
Matrix Scientific	75423	http://www.matrixscientific.com/075423.html
MedChem Express	HY-N0191	https://www.medchemexpress.com/search.html?q=HY-N0191&ft=&fa=&fp=
MolPort	MolPort-001-741-138	https://www.molport.com/shop/molecule-link/MolPort-001-741-138
MolPort	MolPort-002-507-305	https://www.molport.com/shop/molecule-link/MolPort-002-507-305
MolPort	MolPort-003-931-008	https://www.molport.com/shop/molecule-link/MolPort-003-931-008
Molcore	CS22456	http://www.molcore.com/CatCS22456.html
Oakwood	78895	http://www.oakwoodchemical.com/ProductsList.aspx?txtSearch=078895
PI Chemicals	PI-28635	http://www.pipharm.com/catalog_products/PI-28635.html
Princeton BioMolecular Research	OSSL_331483	http://www.princetonbio.com/order_online?common_id=OSSL_331483
Selleck Chemicals	S2261	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2261
TargetMol	BBP60056	https://www.targetmol.com/search?keyword=BBP60056
TargetMol	T2898	https://www.targetmol.com/search?keyword=T2898
Tetrahedron	TS59635	http://www.thsci.com/search.do?q=TS59635
Vitas-M Laboratory	BBL010924	http://www.vitasmlab.biz/search/BBL010924
Vitas-M Laboratory	STK801912	http://www.vitasmlab.biz/search/STK801912
eMolecules	1935749	https://orderbb.emolecules.com/search/#?query=1935749
eMolecules	29909141	https://orderbb.emolecules.com/search/#?query=29909141
eMolecules	46012953	https://orderbb.emolecules.com/search/#?query=46012953
eMolecules	49265809	https://orderbb.emolecules.com/search/#?query=49265809
eNovation Chemicals	D378929	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D378929&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-5521128905	https://mcule.com/MCULE-5521128905/
mcule	MCULE-7580934560	https://mcule.com/MCULE-7580934560/
mcule	MCULE-8461763255	https://mcule.com/MCULE-8461763255/

PubMed

Title	Date	PubMed
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods.	2006 Nov	16497524
Andrographolide could inhibit human colorectal carcinoma Lovo cells migration and invasion via down-regulation of MMP-7 expression.	2009 Aug 14	19426720
The human bitter taste receptor hTAS2R50 is activated by the two natural bitter terpenoids andrographolide and amarogentin.	2009 Nov 11	19817411
Herb-drug interaction of Andrographis paniculata extract and andrographolide on the pharmacokinetics of theophylline in rats.	2010 Mar 30	20096675
Different AhR binding sites of diterpenoid ligands from Andrographis paniculata caused differential CYP1A1 induction in primary culture in mouse hepatocytes.	2011 Dec	21963808
Andrographolide down-regulates hypoxia-inducible factor-1α in human non-small cell lung cancer A549 cells.	2011 Feb 1	21134392
Cellular glutathione content modulates the effect of andrographolide on β-naphthoflavone-induced CYP1A1 mRNA expression in mouse hepatocytes.	2011 Feb 4	21094198
Combination therapy with andrographolide and d-penicillamine enhanced therapeutic advantage over monotherapy with d-penicillamine in attenuating fibrogenic response and cell death in the periportal zone of liver in rats during copper toxicosis.	2011 Jan 1	20946909
Stage of action of naturally occurring andrographolides and their semisynthetic analogues against herpes simplex virus type 1 in vitro.	2011 Jun	21259187
Andrographolide causes apoptosis via inactivation of STAT3 and Akt and potentiates antitumor activity of gemcitabine in pancreatic cancer.	2013 Sep 12	23845849
Andrographolide inhibits tumor angiogenesis via blocking VEGFA/VEGFR2-MAPKs signaling cascade.	2014 Jul 25	24814888
Andrographolide sensitizes the cytotoxicity of human colorectal carcinoma cells toward cisplatin via enhancing apoptosis pathways in vitro and in vivo.	2014 May	24563380
Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats.	2014 Oct 1	25110055
Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.	2015 Dec 5	26485141

Patents

Sample Use Guides

In Vivo Use Guide

Coated tablets containing 140 mg andrographolide twice a day orally administered for a period of 24 months.

Route of Administration: Oral

In Vitro Use Guide

Andrographolide (1-30 uM) significantly decreased the levels of iNOS, COX2, IL-6 and TNF-α in murine bone marrow derived macrophage (BMDM) cells under LPS stimulation

Name

Type

Language

ANDROGRAPHOLIDE

Official Name

English

NSC-383468

Code

English

Andrographolide [WHO-DD]

Common Name

English

ANDROGRAPHOLIDE [INCI]

Common Name

English

HMPL004

Code

English

ANDROGRAPHOLIDE [MI]

Common Name

English

ANDROGRAPHOLIDE (CONSTITUENT OF ANDROGRAPHIS) [DSC]

Common Name

English

2(3H)-FURANONE, 3-(2-((1R,4AS,5R,6R,8AS)-DECAHYDRO-6-HYDROXY-5-(HYDROXYMETHYL)-5,8A-DIMETHYL-2-METHYLENE-1-NAPHTHALENYL)ETHYLIDENE)DIHYDRO-4-HYDROXY-, (3E,4S)-

Systematic Name

English

(3E,4S)-3-(2-((1R,4AS,5R,6R,8AS)-DECAHYDRO-6-HYDROXY-5-(HYDROXYMETHYL)-5,8A-DIMETHYL-2-METHYLENE-1-NAPHTHALENYL)ETHYLIDENE)DIHYDRO-4-HYDROXY-2(3H)-FURANONE

Systematic Name

English

ANDROGRAPHOLIDE [USP-RS]

Common Name

English

3.ALPHA.,14,15,18-TETRAHYDROXY-5.BETA.,9.BETA.H,10.ALPHA.-LABDA-8(20),12-DIEN-16-OIC ACID .GAMMA.-LACTONE

Common Name

English

Classification Tree Code System Code

DSLD

2449 (Number of products:2)