Natural Product (NP) Details

General Information of the NP (ID: NP9796)
Name
Betulinic Acid
Synonyms
Mairin; Betulic acid; NSC 113090; CCRIS 6748; 3-Hydroxylup-20(29)-en-28-oic acid; UNII-4G6A18707N; 3beta-Hydroxy-20(29)-lupaene-28-oic acid; EINECS 207-448-8; NSC677578; als-357; NSC 677578; CHEMBL269277; CHEBI:3087; 3beta-Hydroxy-lup-20(29)-en-28-oic acid; 4G6A18707N; Lup-20(29)-en-28-oic acid, 3-hydroxy-, (3beta)-; AK-72848; Lupatic Acid; SMR000445624
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Species Origin Viscum album ...     Click to Show/Hide
Viscum album
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Santalales
Family: Viscaceae
Genus: Viscum
Species: Viscum album
Lythrum salicaria
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Myrtales
Family: Lythraceae
Genus: Lythrum
Species: Lythrum salicaria
Diospyros kaki
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Ericales
Family: Ebenaceae
Genus: Diospyros
Species: Diospyros kaki
Rhododendron ovatum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Ericales
Family: Ericaceae
Genus: Rhododendron
Species: Rhododendron ovatum
Rubus alceifolius
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Rosales
Family: Rosaceae
Genus: Rubus
Species: Rubus alceifolius
Anemone rivularis
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Ranunculales
Family: Ranunculaceae
Genus: Anemone
Species: Anemone rivularis
Tadehagi triquetrum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Fabales
Family: Fabaceae
Genus: Tadehagi
Species: Tadehagi triquetrum
Ziziphus cambodianus
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Rosales
Family: Rhamnaceae
Genus: Ziziphus
Species: Ziziphus cambodianus
Disease Melanoma [ICD-11: 2C30] Phase 1 [1]
Structure
Click to Download Mol
2D MOL

3D MOL

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Formula
C30H48O3
PubChem CID
64971
Canonical SMILES
CC(=C)C1CCC2(C1C3CCC4C5(CCC(C(C5CCC4(C3(CC2)C)C)(C)C)O)C)C(=O)O
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
InChIKey
QGJZLNKBHJESQX-FZFNOLFKSA-N
CAS Number
CAS 472-15-1
Herb ID
HBIN018379
ETMC ID
548
SymMap ID
SMIT02321
TTD Drug ID
D0R9YR
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Cisplatin      Bladder cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression PCNA  Molecule Info 
Pathway MAP
Down-regulation Expression POU5F1  Molecule Info 
Pathway MAP
Down-regulation Expression SOX2  Molecule Info 
Pathway MAP
                    In-vitro Model TE-11 CVCL_1761 Esophageal squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Betulinic acid enhances the chemical sensitivity of esophageal cancer cells to cisplatin by inhibiting cell proliferation, reducing cell stemness, and inducing pyroptosis.
          4-hydroxy-tamoxifen      Cyclic Mastalgia     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression PYGO2  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
MDA-MB-436 CVCL_0623 Invasive breast carcinoma Homo sapiens
MDA-MB-468 CVCL_0419 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Selective estrogen receptor modulators and betulinic acid act synergistically to target ERalpha and SP1 transcription factor dependent Pygopus expression in breast cancer.
          Erlotinib      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CDK6  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation RB1  Molecule Info 
Pathway MAP
Up-regulation Expression SQSTM1  Molecule Info 
Pathway MAP
Down-regulation Expression TYMS  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Loss of mitochondrial membrane potential
                    In-vitro Model HCC827 CVCL_2063 Lung adenocarcinoma Homo sapiens
NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combining betulinic acid with an EGFR TKI improves drug efficacy in EGFR TKI-resistant lung cancer cells.
          Gefitinib      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CDK6  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation RB1  Molecule Info 
Pathway MAP
Up-regulation Expression SQSTM1  Molecule Info 
Pathway MAP
Down-regulation Expression TYMS  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Loss of mitochondrial membrane potential
                    In-vitro Model HCC827 CVCL_2063 Lung adenocarcinoma Homo sapiens
NCI-H1975 CVCL_1511 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combining betulinic acid with an EGFR TKI improves drug efficacy in EGFR TKI-resistant lung cancer cells.
          TNF-related apoptosis inducing ligand      Lung cancer     Click to Show/Hide the Molecular Data of This Drug
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BAD  Molecule Info 
Pathway MAP
Up-regulation Expression BAK  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    In-vitro Model Huh-7 CVCL_0336 Adult hepatocellular carcinoma Homo sapiens
PLC/PRF/5 CVCL_0485 Adult hepatocellular carcinoma Homo sapiens
                    In-vivo Model 5*105 HUH7 cells were subcutaneously injected into the dorsal flanks of 30 male 6-week old Athymic nude mice.
                    Experimental
                    Result(s)		 Betulinic acid promotes TRAIL function on liver cancer progression inhibition through p53/Caspase-3 signaling activation.
          Sorafenib      Renal cell carcinoma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Up-regulation Expression DDIT3  Molecule Info 
Pathway MAP
Down-regulation Expression mTOR  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H358 CVCL_1559 Lung adenocarcinoma Homo sapiens
A-427 CVCL_1055 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination therapy with low concentrations of sorafenib and betulinic acid had the capacity to induce high levels of cell death and abolish clonogenic activity in some NSCLC cell lines regardless of KRAS mutations.
          5-fluorouracil      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression Gli1  Molecule Info 
Pathway MAP
Down-regulation Expression GLI2  Molecule Info 
Pathway MAP
Down-regulation Expression IGF2  Molecule Info 
Pathway MAP
Down-regulation Expression PTCH1  Molecule Info 
Pathway MAP
                    In-vitro Model OVCAR-3 CVCL_0465 Ovarian serous adenocarcinoma Homo sapiens
Rh30 CVCL_0041 Alveolar rhabdomyosarcoma Homo sapiens
NIH 3T3 CVCL_0594 Healthy Mus musculus
                    Experimental
                    Result(s)		 Sequential treatment with betulinic acid followed by 5-fluorouracil shows synergistic cytotoxic activity in ovarian cancer cells. Ovarian carcinoma cells on concurrent or 5-FU followed by BA treatment show increased Sub-G1 cell population, increased rate of cell apoptosis and morphological changes in mitochondrial membrane.
    β. A List of Drug(s) Whose Resistance can be Reversed by This NP
          Imatinib      Mantle cell lymphoma     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Up-regulation HDAC3 ubiquitination and degradation
                    In-vitro Model K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Betulinic acid restores imatinib sensitivity in BCR-ABL1 kinase-independent, imatinib-resistant chronic myeloid leukemia by increasing HDAC3 ubiquitination and degradation.
Target and Pathway
Target(s) Herpes simplex virus DNA polymerase UL30 (HSV UL30)  Molecule Info  [9]
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3945).
Reference 2 Betulinic acid enhanced the chemical sensitivity of esophageal cancer cells to cisplatin by inducing cell pyroptosis and reducing cell stemness. Ann Palliat Med. 2020 Jul;9(4):1912-1920.
Reference 3 Selective estrogen receptor modulators and betulinic acid act synergistically to target ERalpha and SP1 transcription factor dependent Pygopus expression in breast cancer. J Clin Pathol. 2016 Jun;69(6):518-26.
Reference 4 Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells. Environ Toxicol. 2018 Nov;33(11):1153-1159.
Reference 5 Betulinic acid promotes TRAIL function on liver cancer progression inhibition through p53/Caspase-3 signaling activation. Biomed Pharmacother. 2017 Apr;88:349-358.
Reference 6 Synergistic activity of sorafenib and betulinic acid against clonogenic activity of non-small cell lung cancer cells. Cancer Sci. 2017 Nov;108(11):2265-2272.
Reference 7 Sequential treatment with betulinic acid followed by 5-fluorouracil shows synergistic cytotoxic activity in ovarian cancer cells. Int J Clin Exp Pathol. 2015 Jan 1;8(1):252-9.
Reference 8 Betulinic acid restores imatinib sensitivity in BCR-ABL1 kinase-independent, imatinib-resistant chronic myeloid leukemia by increasing HDAC3 ubiquitination and degradation. Ann N Y Acad Sci. 2020 May;1467(1):77-93.
Reference 9 DNA polymerase beta inhibitors from Tetracera boiviniana. J Nat Prod. 1999 Dec;62(12):1660-3.
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