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
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
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23401880 | https://www.ncbi.nlm.nih.gov/pubmed/24151877
Curator's Comment: Betulinic acid (BA) is able to cross the blood-brain barrier
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26535952
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
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1075164 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12118187 |
5.0 µM [IC50] | ||
Target ID: map04210 |
|||
Target ID: CHEMBL378 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8176401 |
1.4 µM [EC50] | ||
Target ID: CHEMBL1907 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9810272 |
7.3 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
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 |
T1/2
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 |
Funbound
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: 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 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no [IC50 >50 uM] | ||||
no [IC50 >50 uM] | ||||
no | ||||
weak | ||||
yes [IC50 0.1386 uM] | ||||
yes [IC50 1.286 uM] | ||||
yes [IC50 16.98 uM] | ||||
yes [IC50 20.8 uM] | ||||
yes [IC50 21.37 uM] | ||||
yes [IC50 24.06 uM] | ||||
yes | ||||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Acetyl-boswellic acids are novel catalytic inhibitors of human topoisomerases I and IIalpha. | 2000 Jul |
|
Anthelmintic activity of the stem bark extracts of Berlina grandiflora and one of its active principles, Betulinic acid. | 2001 Mar |
|
Antimycobacterial plant terpenoids. | 2001 Nov |
|
Ethnopharmacology and bioinformatic combination for leads discovery: application to phospholipase A(2) inhibitors. | 2001 Nov |
|
Structure and spasmolytic activity of eucalyptanoic acid from Eucalyptus camaldulensis var. obtusa and synthesis of its active derivative from oleanolic acid. | 2002 Dec |
|
Activity-guided fractionation of the seeds of Ziziphus jujuba using a cyclooxygenase-2 inhibitory assay. | 2002 Dec |
|
Betulinic acid, a potent inhibitor of eukaryotic topoisomerase I: identification of the inhibitory step, the major functional group responsible and development of more potent derivatives. | 2002 Jul |
|
Pentacyclic triterpenoids from Ilex macropoda. | 2002 Oct |
|
Anti-AIDS agents 49. Synthesis, anti-HIV, and anti-fusion activities of IC9564 analogues based on betulinic acid. | 2002 Sep 12 |
|
New ursolic and betulinic derivatives as potential cytotoxic agents. | 2003 Apr |
|
Natural anti-HIV agents. Part IV. Anti-HIV constituents from Vatica cinerea. | 2003 Feb |
|
Isolation, characterization and biological activity of betulinic acid and ursolic acid from Vitex negundo L. | 2003 Feb |
|
New cytotoxic lupane triterpenoids from the twigs of Coussarea paniculata. | 2003 Mar |
|
Differential effect of betulin and betulinic acid on cytokine production in human whole blood cell cultures. | 2003 Mar-Apr |
|
[Epimerization of hydroxyl group in the lupan series of triterpenes]. | 2003 Mar-Apr |
|
Broncho-vasodilatory activity of fractions and pure constituents isolated from Bacopa monniera. | 2003 May |
|
Cytotoxic triterpenoids from the fruits of Zizyphus jujuba. | 2003 Nov |
|
Antitumor-promoting constituents from Chaenomeles sinensis KOEHNE and their activities in JB6 mouse epidermal cells. | 2003 Nov |
|
Lupane triterpenes and derivatives with antiviral activity. | 2003 Oct 20 |
|
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 |
|
Betulinic acid: a promising anticancer candidate. | 2004 Apr |
|
Synthesis and cytotoxic activity of 3-O-acyl/3-hydrazine /2-bromo/20,29-dibromo betulinic acid derivatives. | 2004 Aug 2 |
|
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 |
|
Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. | 2004 Jan |
|
Erythrocyte membrane modifying agents and the inhibition of Plasmodium falciparum growth: structure-activity relationships for betulinic acid analogues. | 2004 Jan 2 |
|
Differential expression of three oxidosqualene cyclase mRNAs in Glycyrrhiza glabra. | 2004 Jul |
|
Cell death induction by betulinic acid, ceramide and TRAIL in primary glioblastoma multiforme cells. | 2004 Jul |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00346502
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12118187
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
Edited
Fri Dec 15 16:24:16 GMT 2023
by
admin
on
Fri Dec 15 16:24:16 GMT 2023
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Record UNII |
4G6A18707N
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C2139
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FDA ORPHAN DRUG |
244107
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C38126
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C002070
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m2463
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DTXSID80861974
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BETULINIC ACID
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