Natural Product (NP) Details

General Information of the NP (ID: NP6459)
Name
Vinblastine
Synonyms
vinblastine; Vinblastin; Vincaleucoblastin; Vincaleukoblastine; 865-21-4; Velban; Velbe; UNII-5V9KLZ54CY; CHEMBL159; 29060-LE; 5V9KLZ54CY; Vincoblastine; Rozevin; Nincaluicolflastine; Vinblastina; Vinblastinum; Vinblastina [DCIT]; Vinblastine [INN:BAN]; Vinblastinum [INN-Latin]; (2ALPHA,2'BETA,3BETA,4ALPHA,5BETA)-VINCALEUKOBLASTINE; VR-8; VLB; methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-4-[(13S,15R,17S)-17-ethyl-17-hydroxy-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraen-13-yl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate; CCRIS 9002; HSDB 3263; C46H58N4O9; NCI-C04842; NDC 0002-1452-01; EINECS 212-734-0; NSC 47842; cid_5388983; 2'-Epivinblastine; [3H]-Vinblastine; 1z2b; (2'R)-Vincaleukoblastine; SCHEMBL3628; BIDD:PXR0201; BSPBio_001228; (3aR-(3aalpha,4beta,5beta,5abeta,9(3R*,5S*,7R*,9S*),10bR*,13aalpha))-methyl 4-(acetyloxy)-3a-ethyl-9-(5-ethyl-1,4,5,6,7,8,9,10-octahydro-5-hydroxy-9-(methoxycarbonyl)-2H-3,7-methanoazacycloundecino(5,4-b)indol-9-yl)-3a,4,5,5a,6,11,12,13a-octahydro-5-hydroxy-8-methoxy-6-methyl-1H-indolizino(8,1-cd)carbazole-5-carboxylate; 1H-Indolizino(8,1-cd)carbazole-5-carboxylic acid, 4-(acetyloxy)-3a-ethyl-9-(5-ethyl-1,4,5,6,7,8,9,10-octahydro-5-hydroxy-9-(methoxycarbonyl)-2H-3,7-methanoazacycloundecino(5,4-b)indol-9-yl)-3a,4,5,5a,6,11,12,13a-octahydro-5-hydroxy-8-methoxy-6-methyl-, methyl ester, (3aR-(3aalpha,4beta,5beta,5abeta,9(3R*,5S*,7R*,9S*),10bR*,13aalpha))-; GTPL6851; 132142-72-4; BDBM50012278; NSC-47842; ZINC85432544; AKOS015965500; CS-1336; DB00570; MCULE-9967454324; NCGC00022585-04; NCGC00022585-05; NCGC00485975-02; 72401-36-6; AC-24191; AS-15821; HY-17418; Q943; W-5281; 139299-EP2270008A1; 139299-EP2292617A1; BRD-K01188359-001-02-0; BRD-K01188359-065-02-5; (2alpha,2'beta,3alpha,5beta,19beta)-vincaleukoblastine; (2ALPHA,2''''BETA,3BETA,4ALPHA,5BETA)-VINCALEUKOBLASTINE; methyl (3aR,3a1R,4R,5S,5aR,10bR)-4-acetoxy-3a-ethyl-9-((5S,7R,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-1,4,5,6,7,8,9,10-octahydro-2H-3,7-methano[1]azacycloundecino[5,4-b]indol-9-yl)-5-hydroxy-8-methoxy-6-methyl-3a,3a1,4,5,5a,6,11,12-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate
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Species Origin Catharanthus roseus ...     Click to Show/Hide
Catharanthus roseus
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Gentianales
Family: Apocynaceae
Genus: Catharanthus
Species: Catharanthus roseus
Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z] Approved [1]
Structure
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2D MOL

3D MOL

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Formula
C46H58N4O9
PubChem CID
13342
Canonical SMILES
CCC1(CC2CC(C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)C78CCN9C7C(C=CC9)(C(C(C8N6C)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC)O
InChI
1S/C46H58N4O9/c1-8-42(54)23-28-24-45(40(52)57-6,36-30(15-19-49(25-28)26-42)29-13-10-11-14-33(29)47-36)32-21-31-34(22-35(32)56-5)48(4)38-44(31)17-20-50-18-12-16-43(9-2,37(44)50)39(59-27(3)51)46(38,55)41(53)58-7/h10-14,16,21-22,28,37-39,47,54-55H,8-9,15,17-20,23-26H2,1-7H3/t28-,37-,38+,39+,42-,43+,44+,45-,46-/m0/s1
InChIKey
JXLYSJRDGCGARV-CFWMRBGOSA-N
CAS Number
CAS 865-21-4
Herb ID
HBIN047936
TTD Drug ID
D0W9MM
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Nanoliposomal C6-ceramide      Hepatocellular 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 [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
                    In-vitro Model LS174T CVCL_1384 Colon adenocarcinoma Homo sapiens
Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    In-vivo Model Tumor cells were inoculated into the left flank of 7 week-old female athymic nude mice by subcutaneous injection of 6 * 106 LS174T cells in 0.1 mL Hanks Balanced Salt Solution.
                    Experimental
                    Result(s)		 In vitro and in vivo data support a synergistic antitumor activity of the nanoliposomal C6-ceramide and vinblastine combination, potentially mediated by an autophagy mechanism.
          Temsirolimus      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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression EIF4EBP1  Molecule Info 
Pathway MAP
Down-regulation Expression mTOR  Molecule Info 
Pathway MAP
Down-regulation Expression S6K1  Molecule Info 
Pathway MAP
                    In-vitro Model Hep 3B2.1-7 CVCL_0326 Childhood hepatocellular carcinoma Homo sapiens
Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
PLC/PRF/5 CVCL_0485 Adult hepatocellular carcinoma Homo sapiens
SNU-398 CVCL_0077 Adult hepatocellular carcinoma Homo sapiens
                    In-vivo Model HCC cells (2 * 106 of Huh7 cells or 3 * 106 of Hep3B cells suspended in 200 ul serum free medium) were inoculated into the dorsal flanks of male athymic nude mice (nu/nu) by subcutaneous injection.
                    Experimental
                    Result(s)		 The potent anti-cancer activity of this co-targeting strategy was indeed mediated in parts by inhibition of these key survival/anti-apoptotic proteins.
          Bleomycin      Hodgkin lymphoma     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 [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 The combination of vinblastine and bleomycin achieved a high rate of objective responses in a subgroup of elderly and symptomatic patients, without considerable toxicity.
          Chlorambucil + Procarbazine     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 [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 The treatment of advanced and recurrent Hodgkin's disease with chlorambucil, vinblastine, procarbazine and prednisone in combination.
          Docetaxel + Tamoxifen     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
                    In-vitro Model NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination therapy of breast and lung cancer cell lines using docetaxel or vinblastine with tamoxifen synergistically increases the anti-proliferative affect of single agents.
          Methotrexate + Radiation     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
                    Experimental
                    Result(s)		 Low-dose chemotherapy with methotrexate and vinblastine for 1 year was effective and well tolerated by adult patients with aggressive, recurrent fibromatosis.
          Brentuximab vedotin + Doxorubicin + Dacarbazine     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 [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 The results of the ECHELON-1 study showed a significantly longer modified progression-free survival (mPFS) following BV+AVD than with ABVD in primary HL.
Target and Pathway
Target(s) Tubulin beta-2 chain (TUBB2)  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: 6851).
Reference 2 Synergistic combination therapy with nanoliposomal C6-ceramide and vinblastine is associated with autophagy dysfunction in hepatocarcinoma and colorectal cancer models. Cancer Lett. 2013 Sep 1;337(2):254-65.
Reference 3 Sustained antitumor activity by co-targeting mTOR and the microtubule with temsirolimus/vinblastine combination in hepatocellular carcinoma. Biochem Pharmacol. 2012 May 1;83(9):1146-58.
Reference 4 Combination of vinblastine and bleomycin as first line therapy in advanced classic Kaposi's sarcoma. J Eur Acad Dermatol Venereol. 2006 Oct;20(9):1090-4.
Reference 5 The treatment of advanced and recurrent Hodgkin's disease with chlorambucil, vinblastine, procarbazine and prednisone in combination. Cancer Treat Rev. 1979 Jun;6 Suppl:107-13.
Reference 6 Combination therapy increases the efficacy of docetaxel, vinblastine and tamoxifen in cancer cells. J Cancer Res Ther. Jul-Sep 2014;10(3):715-21.
Reference 7 Combination chemotherapy with methotrexate and vinblastine for surgically unresectable, aggressive fibromatosis. Jpn J Clin Oncol. 2016 Sep;46(9):845-9.
Reference 8 Methotrexate-associated Hodgkin Lymphoma in a Patient with Rheumatoid Arthritis Successfully Treated with Brentuximab Vedotin in Combination with Doxorubicin, Vinblastine, and Dacarbazine (BV+AVD). Intern Med. 2020 Sep 1;59(17):2165-2171.
Reference 9 Effect of the antitumor drug vinblastine on nuclear betaII-tubulin in cultured rat kidney mesangial cells. Invest New Drugs. 2003 Feb;21(1):15-20.
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