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Details

Stereochemistry ABSOLUTE
Molecular Formula C46H56N4O10
Molecular Weight 824.9576
Optical Activity UNSPECIFIED
Defined Stereocenters 9 / 9
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VINCRISTINE

SMILES

CC[C@]1(O)C[C@@H]2CN(C1)CCC3=C(NC4=C3C=CC=C4)[C@@](C2)(C(=O)OC)C5=C(OC)C=C6N(C=O)[C@@H]7[C@]8(CCN9CC=C[C@](CC)([C@@H]89)[C@@H](OC(C)=O)[C@]7(O)C(=O)OC)C6=C5

InChI

InChIKey=OGWKCGZFUXNPDA-CFWMRBGOSA-N
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-/m0/s1

HIDE SMILES / InChI

Molecular Formula C46H56N4O10
Molecular Weight 824.9576
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 9 / 9
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/vincristine.html

Vincristine is a vinca alkaloid antineoplastic agent used as a treatment for various cancers including breast cancer, Hodgkin's disease, Kaposi's sarcoma, and testicular cancer. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units, vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vincristine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vincristine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific. The antitumor activity of Vincristine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, Vincristine may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca2+-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis.Vincristine was marketed under the brand name Oncovin, but was discontinued. In 2012 the FDA approved a Liposomal formulation of Vincristine, named MARQIBO KIT.

Originator

Curator's Comment: # Dr. James. Armstrong of Eli Lilly and Company

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P07437
Gene ID: 203068.0
Gene Symbol: TUBB
Target Organism: Homo sapiens (Human)
1.6 µM [IC50]
0.17 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Marqibo

Approved Use

Marqibo® is indicated for the treatment of adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies.

Launch Date

2012
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1220 ng/mL
2.25 mg/m² steady-state, intravenous
dose: 2.25 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
VINCRISTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
14566 ng × h/mL
2.25 mg/m² steady-state, intravenous
dose: 2.25 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
VINCRISTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
25%
VINCRISTINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
2.25 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 2.25 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 2.25 mg/m2, 1 times / week
Sources:
unhealthy, 19-62
Health Status: unhealthy
Age Group: 19-62
Sex: M+F
Sources:
2.4 mg/m2 1 times / week multiple, intravenous
Studied dose
Dose: 2.4 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 2.4 mg/m2, 1 times / week
Sources:
unhealthy, 19-62
Health Status: unhealthy
Age Group: 19-62
Sex: M+F
Sources:
DLT: Motor polyneuropathy, Seizure...
Dose limiting toxicities:
Motor polyneuropathy (grade 3, 14.3%)
Seizure (grade 4, 14.3%)
Hepatotoxicity (grade 4, 14.3%)
Sources:
2.8 mg/m2 3 times / week multiple, intravenous
Highest studied dose
Dose: 2.8 mg/m2, 3 times / week
Route: intravenous
Route: multiple
Dose: 2.8 mg/m2, 3 times / week
Sources:
unhealthy, 32-83
Health Status: unhealthy
Age Group: 32-83
Sex: M+F
Sources:
DLT: Neutropenia, Thrombocytopenia...
Dose limiting toxicities:
Neutropenia (grade 4, 33.3%)
Thrombocytopenia (grade 4, 33.3%)
Obstipation
Myalgia (grade 3, 33.3%)
Sources:
2.4 mg/m2 3 times / week multiple, intravenous
MTD
Dose: 2.4 mg/m2, 3 times / week
Route: intravenous
Route: multiple
Dose: 2.4 mg/m2, 3 times / week
Sources:
unhealthy, 32-83
Health Status: unhealthy
Age Group: 32-83
Sex: M+F
Sources:
2.25 mg/m2 1 times / week multiple, intravenous
Recommended
Dose: 2.25 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 2.25 mg/m2, 1 times / week
Sources:
unhealthy
Disc. AE: Peripheral neuropathy, Tumor lysis syndrome...
AEs leading to
discontinuation/dose reduction:
Peripheral neuropathy (10%)
Tumor lysis syndrome (2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Motor polyneuropathy grade 3, 14.3%
DLT
2.4 mg/m2 1 times / week multiple, intravenous
Studied dose
Dose: 2.4 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 2.4 mg/m2, 1 times / week
Sources:
unhealthy, 19-62
Health Status: unhealthy
Age Group: 19-62
Sex: M+F
Sources:
Hepatotoxicity grade 4, 14.3%
DLT
2.4 mg/m2 1 times / week multiple, intravenous
Studied dose
Dose: 2.4 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 2.4 mg/m2, 1 times / week
Sources:
unhealthy, 19-62
Health Status: unhealthy
Age Group: 19-62
Sex: M+F
Sources:
Seizure grade 4, 14.3%
DLT
2.4 mg/m2 1 times / week multiple, intravenous
Studied dose
Dose: 2.4 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 2.4 mg/m2, 1 times / week
Sources:
unhealthy, 19-62
Health Status: unhealthy
Age Group: 19-62
Sex: M+F
Sources:
Obstipation DLT
2.8 mg/m2 3 times / week multiple, intravenous
Highest studied dose
Dose: 2.8 mg/m2, 3 times / week
Route: intravenous
Route: multiple
Dose: 2.8 mg/m2, 3 times / week
Sources:
unhealthy, 32-83
Health Status: unhealthy
Age Group: 32-83
Sex: M+F
Sources:
Myalgia grade 3, 33.3%
DLT
2.8 mg/m2 3 times / week multiple, intravenous
Highest studied dose
Dose: 2.8 mg/m2, 3 times / week
Route: intravenous
Route: multiple
Dose: 2.8 mg/m2, 3 times / week
Sources:
unhealthy, 32-83
Health Status: unhealthy
Age Group: 32-83
Sex: M+F
Sources:
Neutropenia grade 4, 33.3%
DLT
2.8 mg/m2 3 times / week multiple, intravenous
Highest studied dose
Dose: 2.8 mg/m2, 3 times / week
Route: intravenous
Route: multiple
Dose: 2.8 mg/m2, 3 times / week
Sources:
unhealthy, 32-83
Health Status: unhealthy
Age Group: 32-83
Sex: M+F
Sources:
Thrombocytopenia grade 4, 33.3%
DLT
2.8 mg/m2 3 times / week multiple, intravenous
Highest studied dose
Dose: 2.8 mg/m2, 3 times / week
Route: intravenous
Route: multiple
Dose: 2.8 mg/m2, 3 times / week
Sources:
unhealthy, 32-83
Health Status: unhealthy
Age Group: 32-83
Sex: M+F
Sources:
Peripheral neuropathy 10%
Disc. AE
2.25 mg/m2 1 times / week multiple, intravenous
Recommended
Dose: 2.25 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 2.25 mg/m2, 1 times / week
Sources:
unhealthy
Tumor lysis syndrome 2%
Disc. AE
2.25 mg/m2 1 times / week multiple, intravenous
Recommended
Dose: 2.25 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 2.25 mg/m2, 1 times / week
Sources:
unhealthy
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
likely
yes
yes
yes (co-administration study)
Comment: the total area under the plasma concentration-time curve was 43% smaller in patients who were receiving carbamazepine or phenytoin than in the control group; the concomitant use of strong CYP3A inhibitors should be avoided (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin). Similarly, the concomitant use of strong CYP3A inducers should be avoided (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s Wort)
Page: 31.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Vincristine-induced autonomic neuropathy.
1975 Jul 26
Altered expression of the MYCN oncogene modulates MRP gene expression and response to cytotoxic drugs in neuroblastoma cells.
1999 Apr 29
Pain related behaviour during vincristine-induced neuropathy in rats.
1999 Apr 6
Vincristine revisited.
1999 Feb
[Acute vincristine neurotoxicity in a non-Hodgkin's lymphoma patient with Charcot-Marie-Tooth disease].
1999 May
Vincristine treatment revealing asymptomatic hereditary motor sensory neuropathy type 1A.
1999 Nov
Nerve growth factor prevention of aged-rat sympathetic neuron injury by cisplatin, vincristine and taxol--in vitro explant study.
1999 Oct 22
Bilateral transient hearing loss associated with vincristine therapy: case report.
2000 Dec
[Syndrome of inappropriate secretion of antidiuretic hormone in a patient with myeloid antigen positive acute lymphoblastic leukemia after systemic chemotherapy including vincristine].
2000 Jan
[Establishment of MRP-overexpression subline of bladder carcinoma and its MDR phenotype].
2000 Jul
Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia.
2000 Mar
Cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) for advanced-stage Hodgkin's disease: CALGB 8856.
2001
Discovery of a novel compound: insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death.
2001 Aug 3
Experience with vincristine--associated neurotoxicity.
2001 Jul
Evaluating treatment strategies in chronic lymphocytic leukemia: use of quality-adjusted survival analysis.
2001 Jul
Itraconazole-enhanced vincristine neurotoxicity in a child with acute lymphoblastic leukemia.
2001 Mar
ChlVPP alternating with PABlOE is superior to PABlOE alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation/Central Lymphoma Group randomized controlled trial.
2001 May 18
Delayed functional recovery by vincristine after sciatic nerve crush injury: a mouse model of vincristine neurotoxicity.
2001 May 18
Ischemic heart disease associated with vincristine and doxorubicin chemotherapy.
2001 Nov
Fatal myeloencephalopathy due to accidental intrathecal vincristin administration: a report of two cases.
2001 Oct 15
Inhibition of drug-induced Fas ligand transcription and apoptosis by Bcl-XL.
2001 Sep
Massive cell death of cerebellar granule neurons accompanied with caspase-3-like protease activation and subsequent motor discoordination after intracerebroventricular injection of vincristine in mice.
2002
Effect of thiopental, propofol, and etomidate on vincristine toxicity in PC12 cells.
2002
High-dose chemotherapy in poor-prognosis adult small round-cell tumors: clinical and molecular results from a prospective study.
2002 Apr 15
Epidemiology of Burkitt's lymphoma in Enugu, Nigeria.
2002 Dec
Posttransplantation lymphoproliferative disorder presenting as a unilateral leg mass 10 years after kidney transplantation.
2002 Dec 15
High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter.
2002 Jun
Improvement of combination chemotherapy tolerance by introduction of polycistronic retroviral vector drug resistance genes MGMT and MDR1 into human umbilical cord blood CD34+ cells.
2002 Mar
Gliomatosis cerebri: molecular pathology and clinical course.
2002 Oct
Sexual dimorphism for protein kinase c epsilon signaling in a rat model of vincristine-induced painful peripheral neuropathy.
2003
The effects of chemotherapeutic agents on the regulation of thrombin on cell surfaces.
2003 Jan
NOVP chemotherapy for Hodgkin's disease transiently induces sperm aneuploidies associated with the major clinical aneuploidy syndromes involving chromosomes X, Y, 18, and 21.
2003 Jan 1
Synergistic augmentation of antimicrotubule agent-induced cytotoxicity by a phosphoinositide 3-kinase inhibitor in human malignant glioma cells.
2003 Jul 15
Charcot-Marie-Tooth disease and vincristine.
2003 May-Jun
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: For Intravenous Use Only. Fatal if Given by Other Routes.
Marqibo is liposome-encapsulated vincristine. 2.25 mg/m2 intravenously over 1 hour once every 7 days.
Route of Administration: Intravenous
In Vitro Use Guide
Treatment of macrophage monolayers for 24 h with vincristine (10(-5)-10(-7) M) inhibited the antibody dependent cellular cytotoxicity (ADCC) by PMA stimulated rat macrophages.
Substance Class Chemical
Created
by admin
on Mon Mar 31 17:34:32 GMT 2025
Edited
by admin
on Mon Mar 31 17:34:32 GMT 2025
Record UNII
5J49Q6B70F
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TECNOCRIS
Preferred Name English
VINCRISTINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
(+)-VINCRISTINE
Common Name English
22-OXOVINCALEUKOBLASTINE
Common Name English
VINCALEUKOBLASTINE, 22-OXO-
Common Name English
Vincristine [WHO-DD]
Common Name English
ONCOTCS
Brand Name English
VINCRISTINE [VANDF]
Common Name English
VINCRISTINE [MI]
Common Name English
VINCRISTINE [HSDB]
Common Name English
VINKRISTIN
Common Name English
VCR
Common Name English
LEUROCRISTINE
Common Name English
LEUCRISTINE
Common Name English
vincristine [INN]
Common Name English
VINCRISTIN
Common Name English
Classification Tree Code System Code
WHO-VATC QL01CA02
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
LIVERTOX 1030
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
NCI_THESAURUS C932
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
WHO-ATC L01CA02
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
WHO-ESSENTIAL MEDICINES LIST 8.2
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
NDF-RT N0000007780
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
NDF-RT N0000007780
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
NCI_THESAURUS C67422
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
NDF-RT N0000175612
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
Code System Code Type Description
DRUG BANK
DB00541
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
ChEMBL
CHEMBL90555
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
EVMPD
SUB00059MIG
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
MERCK INDEX
m11453
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY Merck Index
EPA CompTox
DTXSID1032278
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
INN
1440
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
DRUG CENTRAL
2825
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
ECHA (EC/EINECS)
200-318-1
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
NCI_THESAURUS
C933
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
SMS_ID
100000079089
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
RXCUI
11202
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY RxNorm
PUBCHEM
5388993
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
DAILYMED
5J49Q6B70F
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
FDA UNII
5J49Q6B70F
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
CAS
57-22-7
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
WIKIPEDIA
VINCRISTINE
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
MESH
D014750
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
IUPHAR
6785
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
HSDB
3199
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
CHEBI
143658
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
LACTMED
Vincristine
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
CHEBI
28445
Created by admin on Mon Mar 31 17:34:32 GMT 2025 , Edited by admin on Mon Mar 31 17:34:32 GMT 2025
PRIMARY
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Route of Elimination PHARMACOKINETIC
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