BETULINIC ACID

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C30H48O3
Molecular Weight	456.7003
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12[C@@H](CC[C@@]1(CC[C@]3(C)[C@]2([H])CC[C@]4([H])[C@@]5(C)CC[C@H](O)C(C)(C)[C@]5([H])CC[C@@]34C)C(O)=O)C(C)=C

InChI

InChIKey=QGJZLNKBHJESQX-FZFNOLFKSA-N

InChI=1S/C30H48O3/c1-18(2)19-10-15-30(25(32)33)17-16-28(6)20(24(19)30)8-9-22-27(5)13-12-23(31)26(3,4)21(27)11-14-29(22,28)7/h19-24,31H,1,8-17H2,2-7H3,(H,32,33)/t19-,20+,21-,22+,23-,24+,27-,28+,29+,30-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C30H48O3
Molecular Weight	456.7003
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	9 / 10
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19325847 | https://www.ncbi.nlm.nih.gov/pubmed/12118187 | https://www.ncbi.nlm.nih.gov/pubmed/27748864 | https://www.ncbi.nlm.nih.gov/pubmed/8176401 | https://www.ncbi.nlm.nih.gov/pubmed/9810272

Betulinic acid (BA) is a plant-derived pentacyclic triterpenoid that exerts potent anti-cancer effects in vitro and in vivo. It`s anticancer property is linked to its ability to induce apoptotic cell death in cancer cells by triggering the mitochondrial pathway of apoptosis. In contrast to the cytotoxicity of betulinic acid against a variety of cancer types, normal cells and tissue are relatively resistant to betulinic acid, pointing to a therapeutic window. Compounds that exert a direct action on mitochondria present promising experimental cancer therapeutics, since they may trigger cell death under circumstances in which standard chemotherapeutics fail. Thus, mitochondrion-targeted agents such as betulinic acid hold great promise as a novel therapeutic strategy in the treatment of human cancers. Betulinic acid has antiretroviral, antimalarial, and anti-inflammatory properties. Betulinic acid exerts its inhibitory effect by preventing topoisomerase I-DNA interaction as a result of which the 'cleavable complex' is not formed. In consequence, it also acts as an antagonist to camptothecin-mediated cleavage. The antitumor pharmacological effects of BA consist of triggering apoptosis via the mitochondrial pathway, regulating the cell cycle and the angiogenic pathway via factors, including specificity protein transcription factors, cyclin D1 and epidermal growth factor receptor, inhibiting the signal transducer and activator of transcription 3 and nuclear factor‑κB signaling pathways, preventing the invasion and metastasis of tumor cells, and affecting the expression of topoisomerase I, p53 and lamin B1. Betulinic Acid has also been used in trials studying the treatment of Dysplastic Nevus Syndrome. Betulinic acid acts as anti-melanoma agent through inhibiting aminopeptidase N activity with IC50 of 7.3 uM. Betulinic acid is an inhibitor of HIV-1 with EC50 of 1.4 uM.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
DNA topoisomerase 1 16 Target ID: CHEMBL1075164 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12118187	Inhibitor 8297	5.0 µM [IC50]
Apoptosis 155 Target ID: map04210 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26535952 \| https://www.ncbi.nlm.nih.gov/pubmed/19325847	Activator 1430
Human immunodeficiency virus 1 33 Target ID: CHEMBL378 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8176401	Inhibitor 8297	1.4 µM [EC50]
Aminopeptidase N 3 Target ID: CHEMBL1907 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9810272	Inhibitor 8297	7.3 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12118187 https://www.ncbi.nlm.nih.gov/pubmed/19325847 https://www.ncbi.nlm.nih.gov/pubmed/24821543	Primary		Preclinical	Unknown Approved Use Unknown
Malignant melanoma 22 Sources: http://adisinsight.springer.com/drugs/800017884 https://clinicaltrials.gov/ct2/show/NCT00346502 https://www.ncbi.nlm.nih.gov/pubmed/10771474	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
25.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		BETULINIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
25.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		BETULINIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
382.9 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		BETULINIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1113.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		BETULINIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
62.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17596104	200 mg 1 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		BETULINIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.01% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12955738			BETULINIC ACID plasma	Mus musculus population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
250 mg single, oral Highest studied dose Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/17638699 Page: p.3577	unhealthy, ADULT Health Status: unhealthy Condition: HIV infection Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17638699 Page: p.3577	Sources: https://pubmed.ncbi.nlm.nih.gov/17638699 Page: p.3577
200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17596104 Page: p.594	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/17596104 Page: p.594	Sources: https://pubmed.ncbi.nlm.nih.gov/17596104 Page: p.594

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699 UGT1A6 108 UGT1A8 36 CYP2C19 1478 P-gp 1461 OATP1B3 706 ABCB5 4 UGT1A7 21 OATP1B1 788

Drug as perpetrator

Target	Modality	Activity
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30467864/	no [IC50 >50 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30467864/	no [IC50 >50 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30467864/	no
UGT1A7 23	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26957994/	weak
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29462635/	yes [IC50 0.1386 uM]
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29462635/	yes [IC50 1.286 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30467864/	yes [IC50 16.98 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29867487/	yes [IC50 20.8 uM]
ABCB5 4	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29867487/	yes [IC50 21.37 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29867487/	yes [IC50 24.06 uM]
UGT1A6 141	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26957994/	yes
UGT1A8 48	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26957994/	yes

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P003ON9	https://www.1pchem.com/search?query=1P003ON9
A2B Chem	AB71109	http://a2bchem.com/prod/AB71109
AK Scientific	2267AH	https://aksci.com/item_detail.php?cat=2267AH
Alfa Chemistry	113126	http://www.alfa-chemistry.com/search.aspx?q=113126
Alfa Chemistry	ACM25488533	http://www.alfa-chemistry.com/search.aspx?q=ACM25488533
Ambeed	A200416	http://www.ambeed.com/search/Search.html?keyword=A200416
Angene	AGN-PC-0RV191	http://www.angenechemical.com/productshow/AGN-PC-0RV191.html
Apollo Scientific	BIDF1001	http://www.apolloscientific.co.uk/chemical_results.php?qstext=BIDF1001&product_group=%25&search_fieldname=header_search
Apollo Scientific	BIDF1011	http://www.apolloscientific.co.uk/chemical_results.php?qstext=BIDF1011&product_group=%25&search_fieldname=header_search
AstaTech	24063	http://astatechinc.com/CPSResult.php?CRNO=24063
BLD Pharm	BD1981	http://www.bldpharm.com/search/Search.html?keyword=BD1981
BOC Sciences	25488-53-3	http://www.bocsci.com/description.asp?cas=25488-53-3
BOC Sciences	472-15-1	http://www.bocsci.com/description.asp?cas=472-15-1
BioSynth	Q-100500	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/Q-100500
Biopurify Phytochemicals	BP0271	https://www.phytopurify.com/search.do?a=s&searchtype=3&psize=10&q=BP0271&searchhtmp=simplesearch&t=1
Capot Chemical	16912	https://www.capotchem.com/search.do?q=16912
Cayman Chemical	11686	http://www.caymanchem.com/app/template/Product.vm/catalog/11686
Chem Scene	CS-1216	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1216
Chem4Pharma	C4PB282	https://www.chem4pharma.com/product-page/C4PB282
ChemDiv	N066-0053	http://chemistryondemand.com:8080/eShop/search_results.jsp?idnumber=N066-0053
Combi-Blocks	QC-7817	http://www.combi-blocks.com/cgi-bin/find.cgi?QC-7817
Fluorochem	228218	http://www.fluorochem.co.uk/Products/Product?code=228218
Fluorochem	M01408	http://www.fluorochem.co.uk/Products/Product?code=M01408
Lab Seeker	SC-19742	http://www.labseeker.com/search.php?keywords=SC-19742&category=0
LabSeeker	SC-19742	http://www.labseeker.com/search.php?keywords=SC-19742&category=0
Matrix Scientific	90209	http://www.matrixscientific.com/090209.html
MedChem Express	HY-10529	https://www.medchemexpress.com/search.html?q=HY-10529&ft=&fa=&fp=
MolPort	MolPort-003-939-279	https://www.molport.com/shop/molecule-link/MolPort-003-939-279
MolPort	MolPort-007-980-897	https://www.molport.com/shop/molecule-link/MolPort-007-980-897
MolPort	MolPort-039-033-337	https://www.molport.com/shop/molecule-link/MolPort-039-033-337
Molnova	M14569	https://www.molnova.com/en/serch-list.html?keywords=M14569
Ryan Scientific	Genipin	https://ryansci.com/products?q=Genipin&list_q=&search_type=exact
Selleck Chemicals	S3603	http://www.selleckchem.com/search.html?searchDTO.searchParam=S3603
Specs	AK-693/21159019	http://www.specs.net/enter.php?specsid=AK-693/21159019
TargetMol	BBP00043	https://www.targetmol.com/search?keyword=BBP00043
TargetMol	T2830	https://www.targetmol.com/search?keyword=T2830
Tetrahedron	TS71989	http://www.thsci.com/search.do?q=TS71989
TimTec	ST51036120	http://www.echemstore.com/catalogsearch/result/?q=ST51036120
Toronto Research Chemicals	B330250	https://www.trc-canada.com/product-detail/?CatNum=B330250
Vitas-M Laboratory	STL570261	http://www.vitasmlab.biz/search/STL570261
W&J PharmaChem	50A119165	http://wjpharmachem.com/new/searcht.php?keyword=50A119165
eMolecules	215689303	https://orderbb.emolecules.com/search/#?query=215689303
eMolecules	27249357	https://orderbb.emolecules.com/search/#?query=27249357
eMolecules	36726865	https://orderbb.emolecules.com/search/#?query=36726865
eMolecules	42749934	https://orderbb.emolecules.com/search/#?query=42749934
eNovation Chemicals	D628751	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D628751&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-3066570238	https://mcule.com/MCULE-3066570238/
mcule	MCULE-5368790248	https://mcule.com/MCULE-5368790248/

PubMed

Title	Date	PubMed
Quantitative analysis of betulinic acid in mouse, rat and dog plasma using electrospray liquid chromatography/mass spectrometry.	2003	12955738
New ursolic and betulinic derivatives as potential cytotoxic agents.	2003 Apr	12943194
News from the bench.	2003 Dec	15011647
Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages.	2003 Dec	14723345
New lupane derived compounds with pro-apoptotic activity in cancer cells: synthesis and structure-activity relationships.	2003 Dec 4	14640549
Dihydrobetulinic acid induces apoptosis in Leishmania donovani by targeting DNA topoisomerase I and II: implications in antileishmanial therapy.	2003 Jan-Feb	12765337
Betulinic acid-induced programmed cell death in human melanoma cells involves mitogen-activated protein kinase activation.	2003 Jul	12855667
Antiviral activity of betulin, betulinic and betulonic acids against some enveloped and non-enveloped viruses.	2003 Jul	12837369
[Synthesis and antiviral activity of hydrazides and substituted benzalhydrazides of betulinic acid and its derivatives].	2003 May-Jun	12845810
Cytotoxic triterpenoids from the fruits of Zizyphus jujuba.	2003 Nov	14735446
A new acylated oleanane triterpenoid from Couepia polyandra that inhibits the lyase activity of DNA polymerase beta.	2003 Nov	14640519
Antitumor-promoting constituents from Chaenomeles sinensis KOEHNE and their activities in JB6 mouse epidermal cells.	2003 Nov	14600382
[Synthesis and antiviral activity of ureides and carbamates of betulinic acid and its derivatives].	2003 Nov-Dec	14743541
Antiplasmodial triterpenes from twigs of Gardenia saxatilis.	2003 Oct	12963155
Lupane triterpenes and derivatives with antiviral activity.	2003 Oct 20	14505668
Betulinic acid: a new cytotoxic compound against malignant head and neck cancer cells.	2003 Sep	12953308
Betulinic acid suppresses carcinogen-induced NF-kappa B activation through inhibition of I kappa B alpha kinase and p65 phosphorylation: abrogation of cyclooxygenase-2 and matrix metalloprotease-9.	2003 Sep 15	12960358
Apoptosis of human carcinoma cells in the presence of potential anti-cancer drugs: III. Treatment of Colo-205 and SKBR3 cells with: cis -platin, Tamoxifen, Melphalan, Betulinic acid, L-PDMP, L-PPMP, and GD3 ganglioside.	2004	15454695
Cytotoxic lupane-type triterpenoids from Acacia mellifera.	2004 Apr	15110698
Betulinic acid: a promising anticancer candidate.	2004 Apr	15057642
Marmenol: a 7-geranyloxycoumarin from the leaves of Aegle marmelos Corr.	2004 Apr	14984087
Betulinic acid augments the inhibitory effects of vincristine on growth and lung metastasis of B16F10 melanoma cells in mice.	2004 Apr 19	15083202
Rapid analysis of triterpenic acids by liquid chromatography using porous graphitic carbon and evaporative light scattering detection.	2004 Aug	15352713
[Inhibitory effects of some traditional medicines on proliferation of HIV-1 and its protease].	2004 Aug	15297721
Betulinic acid-induced apoptosis in leukemia cells.	2004 Aug	15201849
Synthesis and cytotoxic activity of 3-O-acyl/3-hydrazine /2-bromo/20,29-dibromo betulinic acid derivatives.	2004 Aug 2	15225732
Phenolic compounds obtained from stems of Couepia ulei with the potential to induce quinone reductase.	2004 Feb	15022717
Antiplasmodial constituents of Cajanus cajan.	2004 Feb	15022164
Phytotoxic and antimicrobial constituents of Bacopa monnieri and Holmskioldia sanguinea.	2004 Feb	15022161
Apoptosis-modulating agents in combination with radiotherapy-current status and outlook.	2004 Feb 1	14751526
Role of the ectodomain of the gp41 transmembrane envelope protein of human immunodeficiency virus type 1 in late steps of the membrane fusion process.	2004 Jan	14694113
New prenylated isoflavanones and other constituents of Lespedeza bicolor.	2004 Jan	14693230
Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection.	2004 Jan	14595673
Erythrocyte membrane modifying agents and the inhibition of Plasmodium falciparum growth: structure-activity relationships for betulinic acid analogues.	2004 Jan 2	14697777
Synthesis of A-seco derivatives of betulinic acid with cytotoxic activity.	2004 Jul	15270560
Differential expression of three oxidosqualene cyclase mRNAs in Glycyrrhiza glabra.	2004 Jul	15256745
Betulinic acid enhances 1alpha,25-dihydroxyvitamin D3-induced differentiation in human HL-60 promyelocytic leukemia cells.	2004 Jul	15205607
Cell death induction by betulinic acid, ceramide and TRAIL in primary glioblastoma multiforme cells.	2004 Jul	15197616
Antitubercular constituents of Valeriana laxiflora.	2004 Jun	15229801
New 3-O-acyl betulinic acids from Strychnos vanprukii Craib.	2004 Jun	15217281
Isolation and structure of gustastatin from the Brazilian nut tree Gustavia hexapetala.	2004 Jun	15217278
Quantitative analysis of anti-inflammatory and radical scavenging triterpenoid esters in evening primrose oil.	2004 Jun 2	15161190
Synthesis of 3-O-acyl/3-benzylidene/3-hydrazone/3-hydrazine/17-carboxyacryloyl ester derivatives of betulinic acid as anti-angiogenic agents.	2004 Jun 21	15149668
The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O-{3',3'-dimethylsuccinyl}-betulinic acid.	2004 Jun 29	15225375
Lipoxygenase inhibition by anadanthoflavone, a new flavonoid from the aerial parts of Anadenanthera colubrina.	2004 Mar	15114507
Steroids and triterpenes from Eleocharis acutangula and E. sellowiana (Cyperaceae).	2004 Mar-Apr	15116945
Betulinic acid and its derivatives as anti-angiogenic agents.	2004 May 3	15081004
Protection of Ewing's sarcoma family tumor (ESFT) cell line SK-N-MC from betulinic acid induced apoptosis by alpha-DL-tocopherol.	2004 Nov 2	15451550
Cooperation of betulinic acid and TRAIL to induce apoptosis in tumor cells.	2004 Oct 7	15361826
Apoptotic activity of betulinic acid derivatives on murine melanoma B16 cell line.	2004 Sep 13	15363977

Patents

Sample Use Guides

In Vivo Use Guide

Treatment will consist of four weeks of daily application of 20% BA ointment to the dysplastic nevi, after which it will be removed surgically and examined. A similar dysplastic nevi will be removed as a control. Four groups of patients will be enrolled. The first group will apply the ointment once a day, the second twice a day, the third three times a day, and the fourth four times a day.

Route of Administration: Topical

In Vitro Use Guide

Betulinic acid inhibits rat topoisomerase I in a dose dependent manner, with complete inhibition of enzyme activity achieved at 10 uM concentration. Betulinic acid at a concentration of 2.5 uM does not inhibit the enzyme activity whereas at 5 uM concentration 50% inhibition is achieved.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:24:16 GMT 2023` Edited by `admin` on `Fri Dec 15 16:24:16 GMT 2023`
Record UNII	4G6A18707N
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BETULINIC ACID

Official Name

English

LUP-20(29)-EN-28-OIC ACID, 3.BETA.-HYDROXY-

Systematic Name

English

NSC-677578

Code

English

BETULINIC ACID [INCI]

Common Name

English

ALS-357

Code

English

BETULIC ACID

Common Name

English

.BETA.-BETULINIC ACID

Common Name

English

BETULINIC ACID [MI]

Common Name

English

LUPATIC ACID

Common Name

English

(3.BETA.)-3-HYDROXYLUP-20(29)-EN-28-OIC ACID

Common Name

English

NSC-113090

Code

English

MAIRIN

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2139