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Details

Stereochemistry ABSOLUTE
Molecular Formula C46H56N4O10.H2O4S
Molecular Weight 923.039
Optical Activity UNSPECIFIED
Defined Stereocenters 10 / 10
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VINCRISTINE SULFATE

SMILES

CC[C@@]1(C[C@@]2([H])C[C@](c3cc4c(cc3OC)N(C=O)[C@]5([H])[C@@]64CCN7CC=C[C@](CC)([C@@]67[H])[C@]([H])([C@@]5(C(=O)OC)O)OC(=O)C)(c8c(CCN(C2)C1)c9ccccc9[nH]8)C(=O)OC)O.OS(=O)(=O)O

InChI

InChIKey=AQTQHPDCURKLKT-PNYVAJAMSA-N
InChI=1S/C46H56N4O10.H2O4S/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;1-5(2,3)4/h9-13,15,20-21,26,28,37-39,47,55-56H,7-8,14,16-19,22-25H2,1-6H3;(H2,1,2,3,4)/t28-,37-,38+,39+,42-,43+,44+,45-,46-;/m0./s1

HIDE SMILES / InChI

Molecular Formula C46H56N4O10
Molecular Weight 824.9594
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 8 / 9
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula H2O4S
Molecular Weight 98.0796
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: 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

TargetsConditions

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

1344384000000
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
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Vincristine-induced myocardial infarction.
1975 Dec
Vincristine-induced autonomic neuropathy.
1975 Jul 26
Fatal myeloencephalopathy due to intrathecal vincristine administration.
1992
Combined intra-arterial and systemic chemotherapy for recurrent malignant brain tumors.
1992 Feb
Vincristine neurotoxicity.
1992 Mar
[Establishment of MRP-overexpression subline of bladder carcinoma and its MDR phenotype].
2000 Jul
[An experimental study on the blood vessel sclerosing therapeutic agents for cavernous hemangiomas].
2001 Aug
Experience with vincristine--associated neurotoxicity.
2001 Jul
Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group.
2001 May
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
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
Effect of thiopental, propofol, and etomidate on vincristine toxicity in PC12 cells.
2002
Different peripheral mechanisms mediate enhanced nociception in metabolic/toxic and traumatic painful peripheral neuropathies in the rat.
2002
Stereoselective transport of hydrophilic quaternary drugs by human MDR1 and rat Mdr1b P-glycoproteins.
2002 Apr
High-dose chemotherapy in poor-prognosis adult small round-cell tumors: clinical and molecular results from a prospective study.
2002 Apr 15
Hyponatremia and syndrome of inappropriate anti-diuretic hormone reported with the use of Vincristine: an over-representation of Asians?
2002 Apr-May
Epidemiology of Burkitt's lymphoma in Enugu, Nigeria.
2002 Dec
Identification and characterization of the canine multidrug resistance-associated protein.
2002 Dec
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
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
Primary cardiac lymphoma--a case report.
2002 Mar-Apr
A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma: continuous infusion doxorubicin, vincristine, and etoposide with daily mitotane as a P-glycoprotein antagonist.
2002 May 1
A novel case of a CAT to AAT transversion in codon 179 of the p53 gene in a supratentorial primitive neuroectodermal tumor harbored by a young girl. Case report and review of the literature.
2003
Sexual dimorphism for protein kinase c epsilon signaling in a rat model of vincristine-induced painful peripheral neuropathy.
2003
Altered temporal pattern of evoked afferent activity in a rat model of vincristine-induced painful peripheral neuropathy.
2003
Enteropathy-associated T-cell lymphoma of the jejunum complicated with intestinal perforation.
2003 Apr
[Clinical analysis of 75 patients with nasopharyngeal non-Hodgkin's lymphoma].
2003 Apr
Vincristine-induced neuropathy as the initial presentation of charcot-marie-tooth disease in acute lymphoblastic leukemia: a Pediatric Oncology Group study.
2003 Apr
[Anaphylaxia induced by etoposide--a case report].
2003 Aug
Henoch-Schönlein IgA glomerulonephritis complicating myeloma kidneys: case report.
2003 Aug
Evidence for an antihyperalgesic effect of venlafaxine in vincristine-induced neuropathy in rat.
2003 Aug 1
The effects of chemotherapeutic agents on the regulation of thrombin on cell surfaces.
2003 Jan
Vincristine neurotoxicity in the presence of hereditary neuropathy.
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
Toxic neuropathy in patients with pre-existing neuropathy.
2003 Jan 28
Synergistic augmentation of antimicrotubule agent-induced cytotoxicity by a phosphoinositide 3-kinase inhibitor in human malignant glioma cells.
2003 Jul 15
Bilateral hearing loss during vincristine therapy: a case report.
2003 Jun
Spinal sensitization mechanism in vincristine-induced hyperalgesia in mice.
2003 Jun 5
Cloning and functional characterization of the multidrug resistance-associated protein (MRP1/ABCC1) from the cynomolgus monkey.
2003 Mar
Changes in sensory processing in the spinal dorsal horn accompany vincristine-induced hyperalgesia and allodynia.
2003 May
Leiomyosarcoma of urinary bladder following cyclophosphamide therapy: report of two cases.
2003 May
Functional and structural consequences of cysteine substitutions in the NH2 proximal region of the human multidrug resistance protein 1 (MRP1/ABCC1).
2003 May 13
The egr-1 gene is induced by DNA-damaging agents and non-genotoxic drugs in both normal and neoplastic human cells.
2003 May 16
Charcot-Marie-Tooth disease and vincristine.
2003 May-Jun
Functional expression of the multidrug resistance protein 1 in microglia.
2003 Oct
Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma.
2003 Oct 1
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.
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 Jun 25 20:52:16 UTC 2021
Edited
by admin
on Fri Jun 25 20:52:16 UTC 2021
Record UNII
T5IRO3534A
Record Status Validated (UNII)
Record Version
  • Download
Related Record Type
Name Type Language
VINCRISTINE SULFATE
EP   MART.   MI   ORANGE BOOK   USAN   USP   VANDF   WHO-DD   WHO-IP  
USAN  
Official Name English
VINCRISTINE SULFATE [IARC]
Common Name English
VINCRISTINI SULFAS [WHO-IP LATIN]
Common Name English
VINCRISUL
Common Name English
22-OXOVINCALEUKOBLASTINE SULFATE (1:1) (SALT) [WHO-IP]
Common Name English
VINCRISTINE SULFATE [MART.]
Common Name English
37231
Code English
LEUROCRISTINE SULFATE (1:1) (SALT)
Common Name English
NSC-67574
Code English
VINCRISTINE SULFATE [USAN]
Common Name English
VINCRISTINE SULFATE [EP MONOGRAPH]
Common Name English
VINCRISTINE SULFATE [USP-RS]
Common Name English
KYOCRISTINE
Common Name English
VINCRISTINE SULFATE [WHO-DD]
Common Name English
VINCALEUKOBLASTINE, 22-OXO-, SULFATE (1:1) (SALT)
Common Name English
VINCRISTINE SULFATE [VANDF]
Common Name English
ONCOVIN
Brand Name English
VINCRISTINE SULFATE [WHO-IP]
Common Name English
VINCREX
Brand Name English
VINCRISTINE SULFATE [MI]
Common Name English
VINCRISTINE SULPHATE
Common Name English
NOVOPHARM
Common Name English
LILLY-37231
Code English
VINCRISTINE SULFATE [USP MONOGRAPH]
Common Name English
VINCRISTINE SULFATE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 259108
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
EU-Orphan Drug EU/3/08/555
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
NCI_THESAURUS C932
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
NCI_THESAURUS C67422
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
Code System Code Type Description
MERCK INDEX
M11453
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY Merck Index
EPA CompTox
2068-78-2
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY
PUBCHEM
5388992
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
VINCRISTINE SULFATE
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY Description: A white to slightly yellow, amorphous or crystalline powder; odourless. Solubility: Freely soluble in water; slightly soluble in ethanol (~750 g/l) TS; practically insoluble in ether R. Category: Cytotoxic drug. Storage: Vincristine sulfate should be kept in a tightly closed container, protected from light, and stored at a temperature between 2 and 8?C. Additional information: Vincristine sulfate is hygroscopic and very toxic. CAUTION: Vincristine sulfate must be handled with care, avoiding contact with the skin and inhalation of airborne particles. Definition: Vincristine sulfate contains not less than 95.0% and not more than 105.0% of C46H56N4O10,H2SO4, calculated with reference to the dried substance.
DRUG BANK
DBSALT000314
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY
NCI_THESAURUS
C1739
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY
USP_CATALOG
1714007
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY USP-RS
EVMPD
SUB05101MIG
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY
CAS
2068-78-2
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY
FDA UNII
T5IRO3534A
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY
HSDB
2068-78-2
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY
ChEMBL
CHEMBL90555
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY
RXCUI
11203
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY
ECHA (EC/EINECS)
218-190-0
Created by admin on Fri Jun 25 20:52:16 UTC 2021 , Edited by admin on Fri Jun 25 20:52:16 UTC 2021
PRIMARY
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PARENT -> SALT/SOLVATE
SUB_CONCEPT->SUBSTANCE
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IMPURITY -> PARENT
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EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
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EP
Related Record Type Details
ACTIVE MOIETY