U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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

[H][C@@]12N3CC[C@@]14C5=CC(=C(OC)C=C5N(C=O)[C@@]4([H])[C@](O)([C@H](OC(C)=O)[C@]2(CC)C=CC3)C(=O)OC)[C@]6(C[C@H]7CN(C[C@](O)(CC)C7)CCC8=C6NC9=CC=CC=C89)C(=O)OC

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 8 / 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
Co-administed with::
dexamethasone, i.v.(40 mg)
Sources: Page: p.1,6
unhealthy, 19-62
n = 18
Health Status: unhealthy
Condition: Acute lymphoblastic leukemia
Age Group: 19-62
Sex: M+F
Population Size: 18
Sources: Page: p.1,6
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
Co-administed with::
dexamethasone, i.v.(40 mg)
Sources: Page: p.1,6
unhealthy, 19-62
n = 7
Health Status: unhealthy
Condition: Acute lymphoblastic leukemia
Age Group: 19-62
Sex: M+F
Population Size: 7
Sources: Page: p.1,6
DLT: Motor polyneuropathy, Seizure...
Dose limiting toxicities:
Motor polyneuropathy (grade 3, 14.3%)
Seizure (grade 4, 14.3%)
Hepatotoxicity (grade 4, 14.3%)
Sources: Page: p.1,6
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: Page: p.701
unhealthy, 32-83
n = 3
Health Status: unhealthy
Condition: Cancer
Age Group: 32-83
Sex: M+F
Population Size: 3
Sources: Page: p.701
DLT: Neutropenia, Thrombocytopenia...
Dose limiting toxicities:
Neutropenia (grade 4, 33.3%)
Thrombocytopenia (grade 4, 33.3%)
Obstipation
Myalgia (grade 3, 33.3%)
Sources: Page: p.701
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: Page: p.704
unhealthy, 32-83
n = 6
Health Status: unhealthy
Condition: Cancer
Age Group: 32-83
Sex: M+F
Population Size: 6
Sources: Page: p.704
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: Page: p.8
unhealthy
n = 83
Health Status: unhealthy
Condition: Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL)
Population Size: 83
Sources: Page: p.8
Disc. AE: Peripheral neuropathy, Tumor lysis syndrome...
AEs leading to
discontinuation/dose reduction:
Peripheral neuropathy (10%)
Tumor lysis syndrome (2%)
Sources: Page: p.8
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
Co-administed with::
dexamethasone, i.v.(40 mg)
Sources: Page: p.1,6
unhealthy, 19-62
n = 7
Health Status: unhealthy
Condition: Acute lymphoblastic leukemia
Age Group: 19-62
Sex: M+F
Population Size: 7
Sources: Page: p.1,6
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
Co-administed with::
dexamethasone, i.v.(40 mg)
Sources: Page: p.1,6
unhealthy, 19-62
n = 7
Health Status: unhealthy
Condition: Acute lymphoblastic leukemia
Age Group: 19-62
Sex: M+F
Population Size: 7
Sources: Page: p.1,6
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
Co-administed with::
dexamethasone, i.v.(40 mg)
Sources: Page: p.1,6
unhealthy, 19-62
n = 7
Health Status: unhealthy
Condition: Acute lymphoblastic leukemia
Age Group: 19-62
Sex: M+F
Population Size: 7
Sources: Page: p.1,6
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: Page: p.701
unhealthy, 32-83
n = 3
Health Status: unhealthy
Condition: Cancer
Age Group: 32-83
Sex: M+F
Population Size: 3
Sources: Page: p.701
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: Page: p.701
unhealthy, 32-83
n = 3
Health Status: unhealthy
Condition: Cancer
Age Group: 32-83
Sex: M+F
Population Size: 3
Sources: Page: p.701
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: Page: p.701
unhealthy, 32-83
n = 3
Health Status: unhealthy
Condition: Cancer
Age Group: 32-83
Sex: M+F
Population Size: 3
Sources: Page: p.701
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: Page: p.701
unhealthy, 32-83
n = 3
Health Status: unhealthy
Condition: Cancer
Age Group: 32-83
Sex: M+F
Population Size: 3
Sources: Page: p.701
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: Page: p.8
unhealthy
n = 83
Health Status: unhealthy
Condition: Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL)
Population Size: 83
Sources: Page: p.8
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: Page: p.8
unhealthy
n = 83
Health Status: unhealthy
Condition: Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL)
Population Size: 83
Sources: Page: p.8
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 myocardial infarction.
1975 Dec
Animal models for the comparative assessment of neurotoxicity following repeated administration of vinca alkaloids.
1979 Jan
Toxic epidermal necrolysis and graft vs. host disease: a clinical spectrum but a diagnostic dilemma.
1999 Jul
Clinical and electrophysiological studies in vincristine induced neuropathy.
1999 Sep
Mild axonal neuropathy of children during treatment for acute lymphoblastic leukaemia.
2000
Bilateral transient hearing loss associated with vincristine therapy: case report.
2000 Dec
Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein.
2000 Jan
Differential sensitivities of MRP1-overexpressing lung tumor cells to cytotoxic metals.
2000 Jan 3
[Severe hemolysis and SIADH-like symptoms induced by vincristine in an ALL patient with liver cirrhosis].
2000 Nov
Down-regulation of catalase gene expression in the doxorubicin-resistant AML subline AML-2/DX100.
2001 Feb 16
Different peripheral mechanisms mediate enhanced nociception in metabolic/toxic and traumatic painful peripheral neuropathies in the rat.
2002
A case of treatment-related myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemotherapy with autologous stem cell transplantation for non-Hodgkin's lymphoma.
2002 Aug
Treatment results of aggressive B non-Hodgkin's lymphoma in advanced age considering comorbidity.
2002 Dec
Posttransplantation lymphoproliferative disorder presenting as a unilateral leg mass 10 years after kidney transplantation.
2002 Dec 15
Vincristine-induced vocal cord paralysis in an infant.
2002 Feb
A prospective study of P-IMVP-16/CBDCA: a novel salvage chemotherapy for patients with aggressive non-Hodgkin's lymphoma who had previously received CHOP therapy as first-line chemotherapy.
2002 Jun
Evaluation of a 6-month chemotherapy protocol with no maintenance therapy for dogs with lymphoma.
2002 Nov-Dec
The effects of chemotherapeutic agents on the regulation of thrombin on cell surfaces.
2003 Jan
Synergistic augmentation of antimicrotubule agent-induced cytotoxicity by a phosphoinositide 3-kinase inhibitor in human malignant glioma cells.
2003 Jul 15
Functional expression of the multidrug resistance protein 1 in microglia.
2003 Oct
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 Fri Dec 15 14:59:52 GMT 2023
Edited
by admin
on Fri Dec 15 14:59:52 GMT 2023
Record UNII
5J49Q6B70F
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
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
TECNOCRIS
Brand 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 Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
LIVERTOX 1030
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
NCI_THESAURUS C932
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
WHO-ATC L01CA02
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
WHO-ESSENTIAL MEDICINES LIST 8.2
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
NDF-RT N0000007780
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
NDF-RT N0000007780
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
NCI_THESAURUS C67422
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
NDF-RT N0000175612
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
Code System Code Type Description
DRUG BANK
DB00541
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PRIMARY
ChEMBL
CHEMBL90555
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PRIMARY
EVMPD
SUB00059MIG
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PRIMARY
MERCK INDEX
m11453
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PRIMARY Merck Index
EPA CompTox
DTXSID1032278
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PRIMARY
INN
1440
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PRIMARY
DRUG CENTRAL
2825
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PRIMARY
ECHA (EC/EINECS)
200-318-1
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
PRIMARY
NCI_THESAURUS
C933
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PRIMARY
SMS_ID
100000079089
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PRIMARY
RXCUI
11202
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PRIMARY RxNorm
PUBCHEM
5388993
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PRIMARY
DAILYMED
5J49Q6B70F
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
PRIMARY
FDA UNII
5J49Q6B70F
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
PRIMARY
CAS
57-22-7
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
PRIMARY
WIKIPEDIA
VINCRISTINE
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
PRIMARY
MESH
D014750
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PRIMARY
IUPHAR
6785
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PRIMARY
HSDB
3199
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PRIMARY
CHEBI
143658
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
PRIMARY
LACTMED
Vincristine
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
PRIMARY
CHEBI
28445
Created by admin on Fri Dec 15 14:59:52 GMT 2023 , Edited by admin on Fri Dec 15 14:59:52 GMT 2023
PRIMARY
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