U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of BETULINIC ACID

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

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

Curator's Comment: Betulinic acid (BA) is able to cross the blood-brain barrier

Originator

Curator's Comment: Johann Tobias Lowitz (1788) was the first to identify and isolate Betulinic acid (BetA) from the outer bark of white-barked birch trees. He found BetA was a major constituent.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
25.1 μg/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
382.9 μg × h/mL
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
62.1 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.01%
BETULINIC ACID plasma
Mus musculus
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
250 mg single, oral
Highest studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources: Page: p.3577
unhealthy, ADULT
Health Status: unhealthy
Condition: HIV infection
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Sources: 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: Page: p.594
healthy, ADULT
n = 6
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: FASTED
Population Size: 6
Sources: Page: p.594
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Synthesis and anti-HIV activity of 3-alkylamido-3-deoxy-betulinic acid derivatives.
2000 Sep
Anthelmintic activity of the stem bark extracts of Berlina grandiflora and one of its active principles, Betulinic acid.
2001 Mar
Inhibitory effects of triterpenoids and sterols on human immunodeficiency virus-1 reverse transcriptase.
2001 May
Antimycobacterial plant terpenoids.
2001 Nov
New developments in anti-HIV chemotherapy.
2001 Nov
Mitochondrial involvement in tracheary element programmed cell death.
2002 Feb
Betulinic acid sensitization of low pH adapted human melanoma cells to hyperthermia.
2002 Mar-Apr
Preparation of a 24-nor-1,4-dien-3-one triterpene derivative from betulin: a new route to 24-nortriterpene analogues.
2002 May 3
Ursolic acid as a trypanocidal constituent in rosemary.
2002 Nov
Effect of three triterpenoids, lupeol, betulin, and betulinic acid on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils.
2002 Nov
23-Hydroxybetulinic acid-mediated apoptosis is accompanied by decreases in bcl-2 expression and telomerase activity in HL-60 Cells.
2002 Nov 22
Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I.
2002 Sep 1
Quantitative analysis of betulinic acid in mouse, rat and dog plasma using electrospray liquid chromatography/mass spectrometry.
2003
News from the bench.
2003 Dec
Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages.
2003 Dec
Constituents of antibacterial extract of Caesalpinia paraguariensis Burk.
2003 Jan-Feb
Betulinic acid-induced programmed cell death in human melanoma cells involves mitogen-activated protein kinase activation.
2003 Jul
[Epimerization of hydroxyl group in the lupan series of triterpenes].
2003 Mar-Apr
Cytotoxic triterpenoids from the fruits of Zizyphus jujuba.
2003 Nov
[Synthesis and antiviral activity of ureides and carbamates of betulinic acid and its derivatives].
2003 Nov-Dec
Synthesis and cytotoxic activity of A-ring modified betulinic acid derivatives.
2003 Oct 6
A review of natural and modified betulinic, ursolic and echinocystic acid derivatives as potential antitumor and anti-HIV agents.
2003 Sep
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
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
Cytotoxic lupane-type triterpenoids from Acacia mellifera.
2004 Apr
Marmenol: a 7-geranyloxycoumarin from the leaves of Aegle marmelos Corr.
2004 Apr
Rapid analysis of triterpenic acids by liquid chromatography using porous graphitic carbon and evaporative light scattering detection.
2004 Aug
[Inhibitory effects of some traditional medicines on proliferation of HIV-1 and its protease].
2004 Aug
Phenolic compounds obtained from stems of Couepia ulei with the potential to induce quinone reductase.
2004 Feb
Antiplasmodial constituents of Cajanus cajan.
2004 Feb
Phytotoxic and antimicrobial constituents of Bacopa monnieri and Holmskioldia sanguinea.
2004 Feb
Apoptosis-modulating agents in combination with radiotherapy-current status and outlook.
2004 Feb 1
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
New prenylated isoflavanones and other constituents of Lespedeza bicolor.
2004 Jan
Erythrocyte membrane modifying agents and the inhibition of Plasmodium falciparum growth: structure-activity relationships for betulinic acid analogues.
2004 Jan 2
Betulinic acid enhances 1alpha,25-dihydroxyvitamin D3-induced differentiation in human HL-60 promyelocytic leukemia cells.
2004 Jul
New 3-O-acyl betulinic acids from Strychnos vanprukii Craib.
2004 Jun
Isolation and structure of gustastatin from the Brazilian nut tree Gustavia hexapetala.
2004 Jun
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
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
Lipoxygenase inhibition by anadanthoflavone, a new flavonoid from the aerial parts of Anadenanthera colubrina.
2004 Mar
Steroids and triterpenes from Eleocharis acutangula and E. sellowiana (Cyperaceae).
2004 Mar-Apr
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
Cooperation of betulinic acid and TRAIL to induce apoptosis in tumor cells.
2004 Oct 7
Apoptotic activity of betulinic acid derivatives on murine melanoma B16 cell line.
2004 Sep 13
Patents

Sample Use Guides

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
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 Wed Jul 05 23:50:36 UTC 2023
Edited
by admin
on Wed Jul 05 23:50:36 UTC 2023
Record UNII
4G6A18707N
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BETULINIC ACID
INCI   MI  
INCI  
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
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
FDA ORPHAN DRUG 244107
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
Code System Code Type Description
NSC
113090
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
PRIMARY
NCI_THESAURUS
C38126
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
PRIMARY
MESH
C002070
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
PRIMARY
DRUG BANK
DB12480
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
PRIMARY
MERCK INDEX
M2463
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
PRIMARY Merck Index
CHEBI
3087
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
PRIMARY
PUBCHEM
64971
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
PRIMARY
ECHA (EC/EINECS)
207-448-8
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
PRIMARY
FDA UNII
4G6A18707N
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
PRIMARY
CAS
472-15-1
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
PRIMARY
NSC
677578
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
PRIMARY
EPA CompTox
DTXSID80861974
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
PRIMARY
WIKIPEDIA
BETULINIC ACID
Created by admin on Wed Jul 05 23:50:36 UTC 2023 , Edited by admin on Wed Jul 05 23:50:36 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> CONSTITUENT ALWAYS PRESENT
PARENT -> ACTIVE CONSTITUENT ALWAYS PRESENT
PARENT -> CONSTITUENT ALWAYS PRESENT
PARENT -> CONSTITUENT ALWAYS PRESENT