VINCRISTINE

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 Search

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
Sources: http://www.drugbank.ca/drugs/DB00541
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
transformed cell apoptotic process 104 Target ID: GO:0006927 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19137911	Activator 1447
Tubulin beta chain 8 Target ID: P07437 Gene ID: 203068.0 Gene Symbol: TUBB Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00541	Inhibitor 8504
microtubule polymerization 21 Target ID: GO:0046785 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10920282	Inhibitor 8504	1.6 µM [IC50]
CCRF-CEM 4 Target ID: CHEMBL382 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22582991	Inhibitor 8504	0.17 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202497s000lbl.pdf	Primary		Approved 8583	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

C_max

Value	Dose	Co-administered	Analyte	Population
1220 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202497Orig1s000PharmR.pdf	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

Value	Dose	Co-administered	Analyte	Population
14566 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202497Orig1s000PharmR.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
25% OTHER GOV https://www.medsafe.govt.nz/profs/Datasheet/v/Vincristinesulfatempinj.pdf			VINCRISTINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/19708032	unhealthy, 19-62 Health Status: unhealthy Age Group: 19-62 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19708032	Sources: https://pubmed.ncbi.nlm.nih.gov/19708032
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: https://pubmed.ncbi.nlm.nih.gov/19708032	unhealthy, 19-62 Health Status: unhealthy Age Group: 19-62 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19708032	DLT: Motor polyneuropathy, Seizure... Dose limiting toxicities: Motor polyneuropathy (grade 3, 14.3%) Seizure (grade 4, 14.3%) Hepatotoxicity (grade 4, 14.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/19708032
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: https://pubmed.ncbi.nlm.nih.gov/10080616	unhealthy, 32-83 Health Status: unhealthy Age Group: 32-83 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10080616	DLT: Neutropenia, Thrombocytopenia... Dose limiting toxicities: Neutropenia (grade 4, 33.3%) Thrombocytopenia (grade 4, 33.3%) Obstipation Myalgia (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/10080616
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: https://pubmed.ncbi.nlm.nih.gov/10080616	unhealthy, 32-83 Health Status: unhealthy Age Group: 32-83 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10080616	Sources: https://pubmed.ncbi.nlm.nih.gov/10080616
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/202497s011lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/202497s011lbl.pdf	Disc. AE: Peripheral neuropathy, Tumor lysis syndrome... AEs leading to discontinuation/dose reduction: Peripheral neuropathy (10%) Tumor lysis syndrome (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/202497s011lbl.pdf

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/19708032	unhealthy, 19-62 Health Status: unhealthy Age Group: 19-62 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19708032
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: https://pubmed.ncbi.nlm.nih.gov/19708032	unhealthy, 19-62 Health Status: unhealthy Age Group: 19-62 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19708032
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: https://pubmed.ncbi.nlm.nih.gov/19708032	unhealthy, 19-62 Health Status: unhealthy Age Group: 19-62 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19708032
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: https://pubmed.ncbi.nlm.nih.gov/10080616	unhealthy, 32-83 Health Status: unhealthy Age Group: 32-83 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10080616
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: https://pubmed.ncbi.nlm.nih.gov/10080616	unhealthy, 32-83 Health Status: unhealthy Age Group: 32-83 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10080616
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: https://pubmed.ncbi.nlm.nih.gov/10080616	unhealthy, 32-83 Health Status: unhealthy Age Group: 32-83 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10080616
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: https://pubmed.ncbi.nlm.nih.gov/10080616	unhealthy, 32-83 Health Status: unhealthy Age Group: 32-83 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10080616
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/202497s011lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/202497s011lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/202497s011lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/202497s011lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946		substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 1119 P-gp 2052

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202497Orig1s000ClinPharmR.pdf#page=31 Page: 31.0	likely
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202497Orig1s000ClinPharmR.pdf#page=31 Page: 31.0	likely
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17029589/	yes
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202497Orig1s000ClinPharmR.pdf#page=31; https://pubmed.ncbi.nlm.nih.gov/10613614/ Page: 31.0	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) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202497Orig1s000ClinPharmR.pdf#page=31; https://pubmed.ncbi.nlm.nih.gov/10613614/ Page: 31.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/15812674/ Page: 4.0

Sourcing

Vendor/Aggregator	ID	URL
AbovChem LLC	HY-N0488
AK Scientific	E375
Biopurify Phytochemicals	BP1439
Biopurify Phytochemicals	BP1440
BioSynth	Q-201925
BOC Sciences	2068-78-2
Bosche Scientific	V1207
Cayman Chemical	11764
Chem Scene	CS-1778
eMolecules	32176538
eMolecules	50241482
eMolecules	95704370
Hangzhou APIChem Technology	AC-22619
Hangzhou Yuhao Chemical Technology	RT14234
IBScreen	STOCK1N-40733
KeyOrganics	AS-12168
mcule	MCULE-1562099693
mcule	MCULE-3827132352
MedChem Express	HY-N0488
MolPort	MolPort-002-519-272
MolPort	MolPort-003-939-860
MolPort	MolPort-035-789-673
Sigma Aldrich	1714007
Sigma Aldrich	V0400000
Sigma Aldrich	V0400000\|SIAL
Sigma Aldrich	V8388\|SIAL
Sigma Aldrich	V8879\|SIGMA
ZINC	ZINC000085537024	http://zinc15.docking.org/substances/ZINC000085537024

PubMed

Title	Date	PubMed
Vincristine-induced autonomic neuropathy.	1975 Jul 26	1148735
Altered expression of the MYCN oncogene modulates MRP gene expression and response to cytotoxic drugs in neuroblastoma cells.	1999 Apr 29	10348353
Pain related behaviour during vincristine-induced neuropathy in rats.	1999 Apr 6	10321468
Vincristine revisited.	1999 Feb	10226730
[Acute vincristine neurotoxicity in a non-Hodgkin's lymphoma patient with Charcot-Marie-Tooth disease].	1999 May	10390891
Vincristine treatment revealing asymptomatic hereditary motor sensory neuropathy type 1A.	1999 Nov	10519723
Nerve growth factor prevention of aged-rat sympathetic neuron injury by cisplatin, vincristine and taxol--in vitro explant study.	1999 Oct 22	10553948
Bilateral transient hearing loss associated with vincristine therapy: case report.	2000 Dec	11154039
[Syndrome of inappropriate secretion of antidiuretic hormone in a patient with myeloid antigen positive acute lymphoblastic leukemia after systemic chemotherapy including vincristine].	2000 Jan	10660739
[Establishment of MRP-overexpression subline of bladder carcinoma and its MDR phenotype].	2000 Jul	11778547
Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia.	2000 Mar	10741703
Cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) for advanced-stage Hodgkin's disease: CALGB 8856.	2001	11458812
Discovery of a novel compound: insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death.	2001 Aug 3	11478917
Experience with vincristine--associated neurotoxicity.	2001 Jul	11957264
Evaluating treatment strategies in chronic lymphocytic leukemia: use of quality-adjusted survival analysis.	2001 Jul	11438417
Itraconazole-enhanced vincristine neurotoxicity in a child with acute lymphoblastic leukemia.	2001 Mar	11255732
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	11355937
Delayed functional recovery by vincristine after sciatic nerve crush injury: a mouse model of vincristine neurotoxicity.	2001 May 18	11335041
Ischemic heart disease associated with vincristine and doxorubicin chemotherapy.	2001 Nov	11724093
Fatal myeloencephalopathy due to accidental intrathecal vincristin administration: a report of two cases.	2001 Oct 15	11587867
Inhibition of drug-induced Fas ligand transcription and apoptosis by Bcl-XL.	2001 Sep	11716366
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	12401321
Effect of thiopental, propofol, and etomidate on vincristine toxicity in PC12 cells.	2002	11991087
High-dose chemotherapy in poor-prognosis adult small round-cell tumors: clinical and molecular results from a prospective study.	2002 Apr 15	11956280
Epidemiology of Burkitt's lymphoma in Enugu, Nigeria.	2002 Dec	12530287
Posttransplantation lymphoproliferative disorder presenting as a unilateral leg mass 10 years after kidney transplantation.	2002 Dec 15	12490805
High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter.	2002 Jun	12082016
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	11792417
Gliomatosis cerebri: molecular pathology and clinical course.	2002 Oct	12325066
Sexual dimorphism for protein kinase c epsilon signaling in a rat model of vincristine-induced painful peripheral neuropathy.	2003	12809704
The effects of chemotherapeutic agents on the regulation of thrombin on cell surfaces.	2003 Jan	12542493
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	12517776
Synergistic augmentation of antimicrotubule agent-induced cytotoxicity by a phosphoinositide 3-kinase inhibitor in human malignant glioma cells.	2003 Jul 15	12874004
Charcot-Marie-Tooth disease and vincristine.	2003 May-Jun	12756314

Patents

Sample Use Guides

In Vivo Use Guide

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

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Name

Type

Language

TECNOCRIS

Preferred Name

English

VINCRISTINE

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