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  1. General Info
  2. Source Info
  3. Effects Info
  4. Reference
Phytochemical Details
01. General Information
Name Toosendanin
PubChem CID 9851101
Molecular Weight 574.6g/mol
Synonyms

toosendanin

Formula C₃₀H₃₈O₁₁
SMILES CC(=O)OC1CC(C23COC(C1(C2CC(C4(C3C(=O)C(C5(C46C(O6)CC5C7=COC=C7)C)OC(=O)C)C)O)C)O)O
InChI 1S/C30H38O11/c1-13(31)39-20-10-19(34)29-12-38-25(36)26(20,3)17(29)9-18(33)28(5)23(29)22(35)24(40-14(2)32)27(4)16(15-6-7-37-11-15)8-21-30(27,28)41-21/h6-7,11,16-21,23-25,33-34,36H,8-10,12H2,1-5H3/t16-,17-,18+,19-,20+,21+,23-,24-,25+,26+,27+,28+,29+,30+/m0/s1
InChIKey NAHTXVIXCMUDLF-RFNFAWMESA-N
CAS Number 58812-37-6
ChEMBL ID CHEMBL503044
ChEBI ID CHEBI:192461
Herb ID HBIN046550
Structure 2D-img
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2D MOL 3D MOL
02. Source Information of Phytochemical
(1) Melia toosendan Cold
Chineses Pinyin ChuanLianZi
Use Part Fruit
Habitat GanSu, HeNan, HuBei, HuNan, GuiZhou, SiChuan, YunNan
Flavor Bitter
Meridian Tropism Liver, Small intestine, Bladder
Species
>Kingdom: Viridiplantae
 -->Phylum: Streptophyta
  -->Class: Equisetopsida
   -->Order: Sapindales
    -->Family: Meliaceae
     -->Genus: Melia
      -->Species: Melia toosendan
(2) Melia azedarach Cold
Chineses Pinyin KuLanPi
Use Part Dried bark and root bark
Habitat SiChuan, GuiZhou, HuNan, HuBei, HeNan, GanSu
Flavor Bitter
Meridian Tropism Liver; Spleen; Stomach
Species
>Kingdom: Viridiplantae
 -->Phylum: Streptophyta
  -->Class: Equisetopsida
   -->Order: Sapindales
    -->Family: Meliaceae
     -->Genus: Melia
      -->Species: Melia azedarach
03. Combinatorial Therapeutic Effect(s)
Synergistic Effect
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Drug(s) whose efficacy can be enhanced by this phytochemical
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Combination Pair ID: 220
Pair Name Toosendanin, Camptothecin
Partner Name Camptothecin
Disease Info [ICD-11: 2C77] Cervical cancer Investigative
Biological Phenomena Induction-->Autophagy
Gene Regulation Down-regulation Activity ATP6AP2 hsa10159
Down-regulation Expression CTSB hsa1508
Down-regulation Expression CTSD hsa1509
Up-regulation Expression SQSTM1 hsa8878
In Vitro Model HeLa Human papillomavirus-related cervical adenocarcinoma Homo sapiens (Human) CVCL_0030
A-549 Lung adenocarcinoma Homo sapiens (Human) CVCL_0023
In Vivo Model 1×10⁶ HeLa cells stably expressing mRFP-GFP-LC3 were suspended in 100 μL serum-free culture medium and inoculated into the left axilla.
Result These results suggest that toosendanin has the potential to be developed into an anti-cancer drug by blocking chemotherapy-induced protective autophagy.
Combination Pair ID: 221
Pair Name Toosendanin, Irinotecan
Partner Name Irinotecan
Disease Info [ICD-11: 2C60] Breast cancer Investigative
Biological Phenomena Induction-->Autophagy
Gene Regulation Up-regulation Expression CASP3 hsa836
Down-regulation Expression CTSB hsa1508
Down-regulation Expression CTSD hsa1509
In Vitro Model MDA-MB-231 Breast adenocarcinoma Homo sapiens (Human) CVCL_0062
MDA-MB-436 Invasive breast carcinoma Homo sapiens (Human) CVCL_0623
In Vivo Model MDA-MB-231 cells stably expressing RFP-GFP-LC3 were suspended in a 1:1 ratio in serum-free DMEM medium with a matrigel basement membrane matrix and inoculated subcutaneously (5×10⁶/site) in the right armpit.
Result The data showed that TSN blocked 7-ethyl-10-hydroxycamptothecin (SN-38)/irinotecan-induced protective autophagy, and significantly induced apoptosis in TNBC cells and tumor xenograft models when compared to SN-38/irinotecan alone group.
Combination Pair ID: 691
Pair Name Toosendanin, Regorafenib
Partner Name Regorafenib
Disease Info [ICD-11: 2C12] Hepatocellular carcinoma Investigative
Biological Phenomena Inhibition-->Cell metastasis
Gene Regulation Down-regulation Expression DVL2 hsa1856
Up-regulation Phosphorylation GSK3B hsa2932
Down-regulation Expression MMP2 hsa4313
Down-regulation Expression MMP9 hsa4318
Down-regulation Expression MYC hsa4609
Down-regulation Phosphorylation STAT3 hsa6774
Up-regulation Expression WWOX hsa51741
In Vitro Model MHCC97-L Adult hepatocellular carcinoma Homo sapiens (Human) CVCL_4973
Result TSN and RGF combination (TRC) synergistically inhibited the proliferation and migration of MHCC-97L cells. The upregulation of WWOX (WW-domain containing oxidoreductase) played a vital role in the HCC cell growth treated with TRC
Combination Pair ID: 1024
Pair Name Toosendanin, Paclitaxel
Partner Name Paclitaxel
Disease Info [ICD-11: 2C60] Breast cancer Investigative
Biological Phenomena Induction-->Endoplasmic reticulum stress
Gene Regulation Down-regulation Expression ADORA2A hsa135
Down-regulation Expression CASP3 hsa836
Up-regulation Expression CDH1 hsa999
Down-regulation Expression CDH2 hsa1000
Down-regulation Expression CTNNB1 hsa1499
Down-regulation Expression PARP1 hsa142
Down-regulation Expression SNAI1 hsa6615
Down-regulation Expression TWIST1 hsa7291
Down-regulation Expression VIM hsa7431
In Vitro Model MDA-MB-231 Breast adenocarcinoma Homo sapiens (Human) CVCL_0062
BT-549 Invasive breast carcinoma of no special type Homo sapiens (Human) CVCL_1092
4T1 Malignant neoplasms of the mouse mammary gland Mus musculus (Mouse) CVCL_0125
In Vivo Model 2×10⁵ 4T1-fluc-red cells were inoculated in a mammary fat pat of each mouse.
Result The results suggest that combination of TSN and PTX is superior to PTX alone, suggesting that it may be a promising alternative adjuvant chemotherapy strategy for patients with TNBC, especially those with metastatic TNBC.
04. Reference
No. Title Href
1 Toosendanin, a novel potent vacuolar-type H+-translocating ATPase inhibitor, sensitizes cancer cells to chemotherapy by blocking protective autophagy. Int J Biol Sci. 2022 Mar 28;18(7):2684-2702. doi: 10.7150/ijbs.71041. Click
2 Toosendanin, a late-stage autophagy inhibitor, sensitizes triple-negative breast cancer to irinotecan chemotherapy. Chin Med. 2022 May 6;17(1):55. doi: 10.1186/s13020-022-00605-8. Click
3 Synergistic effect of toosendanin and regorafenib against cell proliferation and migration by regulating WWOX signaling pathway in hepatocellular carcinoma. Phytother Res. 2021 Aug;35(8):4567-4578. doi: 10.1002/ptr.7174. Click
4 Synergistic Anti-Tumor Effect of Toosendanin and Paclitaxel on Triple-Negative Breast Cancer via Regulating ADORA2A-EMT Related Signaling. Adv Biol (Weinh). 2023 Aug;7(8):e2300062. doi: 10.1002/adbi.202300062. Click
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