Natural Product (NP) Details

General Information of the NP (ID: NP1644)
Name
Vincristine
Synonyms
LCR; Leurocristine; Marqibo; Oncovine; Tecnocris; VCR; VIN; Vincasar; Vincristina; Vincristinum; Vincrstine; Vincrystine; Vinkristin; Indole alkaloid; Liposomal Vincristine; Onco TCS; Vincristina [DCIT]; Oncovin (TN); Tecnocris (TN); Vincristine (INN); Vincristine [INN:BAN]; Vincristinum [INN-Latin]; Lilly37231 (1:1 sulfate salt); Oncovin (1:1 sulfate salt); Vincasar (1:1 sulfate salt); Vincrex (1:1 sulfate salt); Vincaleukoblastine, 22-oxo-22-Oxovincaleukoblastine; Z-D-Val-Lys(Z)-OH; 22-Oxovincaleukoblastine
    Click to Show/Hide
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 Leukaemia [ICD-11: 2A60-2B33] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -6.168
 
MDCK Permeability
 -5.21
 
PAMPA
 - -
 
HIA
 - - -
 
Distribution
VDss
 0.38
 
PPB
 64.3%
 
BBB
 +
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 +++
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 +++
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 +++
CYP3A4 substrate
 +++
CYP2B6 inhibitor
 ++
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 ++
HLM Stability
 +++
 
Excretion
CLplasma
 3.294
 
T1/2
 1.633
Toxicity
DILI
 ++
 
Rat Oral Acute Toxicity
 ++
 
FDAMDD
 +++
 
Respiratory
 +++
 
Human Hepatotoxicity
 +++
 
Ototoxicity
 +++
 
Drug-induced Nephrotoxicity
 +++
 
Drug-induced Neurotoxicity
 +++
 
Hematotoxicity
 ++
 
Genotoxicity
 +++
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
    Click to Show/Hide
    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C46H56N4O10
PubChem CID
5978
Canonical SMILES
CCC1(CC2CC(C3=C(CCN(C2)C1)C4=CC=CC=C4N3)(C5=C(C=C6C(=C5)C78CCN9C7C(C=CC9)(C(C(C8N6C=O)(C(=O)OC)O)OC(=O)C)CC)OC)C(=O)OC)O
InChI
1S/C46H56N4O10/c1-7-42(55)22-28-23-45(40(53)58-5,36-30(14-18-48(24-28)25-42)29-12-9-10-13-33(29)47-36)32-20-31-34(21-35(32)57-4)50(26-51)38-44(31)16-19-49-17-11-15-43(8-2,37(44)49)39(60-27(3)52)46(38,56)41(54)59-6/h9-13,15,20-21,26,28,37-39,47,55-56H,7-8,14,16-19,22-25H2,1-6H3/t28-,37+,38-,39-,42+,43-,44-,45+,46+/m1/s1
InChIKey
OGWKCGZFUXNPDA-XQKSVPLYSA-N
CAS Number
CAS 57-22-7
ChEBI ID
CHEBI:28445
Herb ID
HBIN047954
SymMap ID
SMIT18173
TTD Drug ID
D09QVV
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Sildenafil      Erectile dysfunction     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 Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP8  Molecule Info 
Pathway MAP
Up-regulation Expression CCNB1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation CDK1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model PC-3 CVCL_0035 Prostate carcinoma Homo sapiens
DU145 CVCL_0105 Prostate carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Phosphodiesterase type 5 inhibitors synergize vincristine in killing castration-resistant prostate cancer through amplifying mitotic arrest signaling.
          VE-465      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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP7  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK2  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation RAD53  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Cell cycle arrest in G2/M-phase
                    In-vitro Model KCL-22 CVCL_2091 Chronic myelogenous leukemia Homo sapiens
K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
Ku812 CVCL_0379 Chronic myelogenous leukemia Homo sapiens
THP-1 CVCL_0006 Childhood acute monocytic leukemia Homo sapiens
HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
U-937 CVCL_0007 Adult acute monocytic leukemia Homo sapiens
KY821 CVCL_1346 Acute myelomonocytic leukemia Homo sapiens
                    Experimental
                    Result(s)		 Vincristine potentiates the anti-proliferative effect of an aurora kinase inhibitor, VE-465, in myeloid leukemia cells.
          Vorinostat      Mycosis fungoides     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
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-xL  Molecule Info 
Pathway MAP
Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression HDAC6  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
Up-regulation Expression PARP1  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Cell cycle arrest in G2/M phase
                    In-vitro Model MOLT-4 CVCL_0013 Adult T acute lymphoblastic leukemia Homo sapiens
CCRF-CEM CVCL_0207 T acute lymphoblastic leukemia Homo sapiens
                    In-vivo Model MOLT-4 cells were implanted (1*107 cells/ml) into severe combined immunodeficiency (SCID) mice.
                    Experimental
                    Result(s)		 The combination of vincristine and SAHA on T cell leukemic cells resulted in a change in microtubule dynamics contributing to M phase arrest followed by induction of the apoptotic pathway.
          Tolfenamic acid      Pancreatic 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 [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BIRC5  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Cell cycle arrest in G2/M phase
                    In-vitro Model Daoy CVCL_1167 Medulloblastoma Homo sapiens
D283 Med CVCL_1155 Medulloblastoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of clotam and vincristine enhances anti-proliferative effect in medulloblastoma cells.
          Combretastatin A-4 phosphate      Rheumatoid arthritis     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		 Up-regulation Expression IL19  Molecule Info 
Pathway MAP
Up-regulation Expression TNF  Molecule Info 
Pathway MAP
Down-regulation Expression TRIM26  Molecule Info 
Pathway MAP
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    In-vivo Model Rats received single I.P injection of Diethylnitrosamine (DENA) 200 mg/kg body weight, freshly dissolved in sterile 0.9% saline, as an inducer for hepatocellular carcinoma.
                    Experimental
                    Result(s)		 CA4-P showed a potential anti-cancer activity against hepatocellular carcinoma and this effect was greatly enhanced by co-administration with vincristine.
          Belinostat      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		 Up-regulation Expression BCL2L11  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    In-vitro Model SU-DHL-4 CVCL_0539 B-cell lymphoma Homo sapiens
DB CVCL_1168 B-cell lymphoma Homo sapiens
OCI-Ly19 CVCL_1878 B-cell lymphoma Homo sapiens
SU-DHL-8 CVCL_2207 B-cell lymphoma Homo sapiens
GM18564 CVCL_P179 Healthy Homo sapiens
                    Experimental
                    Result(s)		 Vincristine sensitizes DLBCL cells to the cytotoxic effects of belinostat.
          Rituximab      Malignant haematopoietic neoplasm     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
                    Biological
                    Regulation		 Increase Tumor cell death
                    In-vitro Model Ramos CVCL_0597 Burkitt lymphoma Homo sapiens
                    Experimental
                    Result(s)		 Rituximab synergizes with vincristine in the killing of Ramos Burkitt's lymphoma B cell line.
          BI-D1870      Mature B-cell leukaemia     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 [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Induction Cell cycle arrest in M phase
                    In-vitro Model KG-1 CVCL_0374 Adult acute myeloid leukemia Homo sapiens
HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
NALM-6 CVCL_0092 Adult B acute lymphoblastic leukemia Homo sapiens
                    Experimental
                    Result(s)		 BI-D1870 induces apoptosis of AML cells alone and in combination with vincristine through blocking mitotic exit, providing a novel approach to overcoming vincristine resistance in AML cells.
          Volasertib      Acute myeloid leukaemia     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 [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model A-204 CVCL_1058 Embryonal rhabdomyosarcoma Homo sapiens
RD CVCL_1649 Embryonal rhabdomyosarcoma Homo sapiens
Rh18 CVCL_1659 Alveolar rhabdomyosarcoma Homo sapiens
Rh30 CVCL_0041 Alveolar rhabdomyosarcoma Homo sapiens
Rh41 CVCL_2176 Alveolar rhabdomyosarcoma Homo sapiens
RMS-1 CVCL_UF94 Embryonal rhabdomyosarcoma Homo sapiens
RMS-YM CVCL_A792 Embryonal rhabdomyosarcoma Homo sapiens
                    Experimental
                    Result(s)		 Volasertib exhibits antitumor activity and synergy with vincristine in alveolar rhabdomyosarcoma.
          Dipyridamole      Hypertension     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 [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model MOLT-3 CVCL_0624 Adult T acute lymphoblastic leukemia Homo sapiens
ML1 CVCL_0436 Adult acute myeloid leukemia Homo sapiens
BL-TH Burkitt's lymphoma Homo sapiens
                    Experimental
                    Result(s)		 Dipyridamole and vincristine combination showed synergistic inhibitory effects on the growth of human leukaemia and lymphoma cell lines.
          Methotrexate      Leukaemia     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 [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model MOLT-3 CVCL_0624 Adult T acute lymphoblastic leukemia Homo sapiens
                    Experimental
                    Result(s)		 Simultaneous exposure of VCR and MTX produced subadditive or mutually protective interactions.
          Topotecan      Ovarian 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 [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model Rh18 CVCL_1659 Alveolar rhabdomyosarcoma Homo sapiens
D283 Med CVCL_1155 Medulloblastoma Homo sapiens
Daoy CVCL_1167 Medulloblastoma Homo sapiens
SJ-GBM2 CVCL_M141 Glioblastoma Homo sapiens
NB-EB Neuroblastoma Homo sapiens
RMSs Embryonal rhabdomyosarcoma Homo sapiens
                    Experimental
                    Result(s)		 The therapeutic effect of combining topotecan with vincristine was greater than additive in most tumor models of childhood solid tumors tested.
Target and Pathway
Target(s) Tubulin beta (TUBB)  Molecule Info  [14]
KEGG Pathway Phagosome Click to Show/Hide
2 Gap junction
3 Pathogenic Escherichia coli infection
NetPath Pathway FSH Signaling Pathway Click to Show/Hide
2 TCR Signaling Pathway
3 EGFR1 Signaling Pathway
Panther Pathway Cytoskeletal regulation by Rho GTPase Click to Show/Hide
2 Huntington disease
Reactome Regulation of PLK1 Activity at G2/M Transition Click to Show/Hide
2 Loss of Nlp from mitotic centrosomes
3 Recruitment of mitotic centrosome proteins and complexes
4 Loss of proteins required for interphase microtubule organization?from the centrosome
5 Anchoring of the basal body to the plasma membrane
WikiPathways Parkin-Ubiquitin Proteasomal System pathway Click to Show/Hide
2 Pathogenic Escherichia coli infection
3 Mitotic G2-G2/M phases
References
Reference 1 FDA Approved Drug Products from FDA Official Website.
Reference 2 Phosphodiesterase Type 5 Inhibitors Synergize Vincristine in Killing Castration-Resistant Prostate Cancer Through Amplifying Mitotic Arrest Signaling. Front Oncol. 2020 Aug 7;10:1274.
Reference 3 Vincristine potentiates the anti-proliferative effect of an aurora kinase inhibitor, VE-465, in myeloid leukemia cells. Biochem Pharmacol. 2011 Dec 15;82(12):1884-90.
Reference 4 The synergic effect of vincristine and vorinostat in leukemia in vitro and in vivo. J Hematol Oncol. 2015 Jul 10;8:82.
Reference 5 Combination of clotam and vincristine enhances anti-proliferative effect in medulloblastoma cells. Gene. 2019 Jul 15;705:67-76.
Reference 6 Enhanced anticancer effect of Combretastatin A-4 phosphate when combined with vincristine in the treatment of hepatocellular carcinoma. Biomed Pharmacother. 2017 May;89:36-46.
Reference 7 Belinostat and vincristine demonstrate mutually synergistic cytotoxicity associated with mitotic arrest and inhibition of polyploidy in a preclinical model of aggressive diffuse large B cell lymphoma. Cancer Biol Ther. 2016 Dec;17(12):1240-1252.
Reference 8 Rituximab synergizes with hydroxyurea or vincristine in the killing of Ramos Burkitt's lymphoma B cell line. Cancer Biother Radiopharm. 2014 Mar;29(2):87-90.
Reference 9 RSK inhibitor BI-D1870 inhibits acute myeloid leukemia cell proliferation by targeting mitotic exit. Oncotarget. 2020 Jun 23;11(25):2387-2403.
Reference 10 Polo-like Kinase Inhibitor Volasertib Exhibits Antitumor Activity and Synergy with Vincristine in Pediatric Malignancies. Anticancer Res. 2016 Feb;36(2):599-609.
Reference 11 Synergistic inhibitory effects of dipyridamole and vincristine on the growth of human leukaemia and lymphoma cell lines. Br J Cancer. 1987 Oct;56(4):413-7.
Reference 12 Effects of vincristine in combination with methotrexate and other antitumor agents in human acute lymphoblastic leukemia cells in culture. Cancer Res. 1988 Jan 15;48(2):351-6.
Reference 13 Synergy of topotecan in combination with vincristine for treatment of pediatric solid tumor xenografts. Clin Cancer Res. 1999 Nov;5(11):3617-31.
Reference 14 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link