Identification
NameVintafolide
Accession NumberDB05168  (DB12503)
TypeSmall Molecule
GroupsInvestigational
Description

Vintafolide is a folate-targeted chemotherapeutic conjugate (folate vitamin + vinca alkaloid) in clinical stage development as a treatment for folate-receptor positive cancers.

Structure
Thumb
SynonymsNot Available
External IDs EC-145 / EC145
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII36O410ZD4I
CAS number742092-03-1
WeightAverage: 1917.06
Monoisotopic: 1915.729405062
Chemical FormulaC86H109N21O26S2
InChI KeyKUZYSQSABONDME-QRLOMCMNSA-N
InChI
InChI=1S/C86H109N21O26S2/c1-6-82(129)35-42-36-85(78(127)132-5,64-47(21-26-106(39-42)41-82)46-12-8-9-13-50(46)95-64)49-30-48-57(34-58(49)131-4)105(3)75-84(48)23-27-107-25-11-22-83(7-2,74(84)107)76(125)86(75,130)77(126)103-104-81(128)133-28-29-134-135-40-56(73(123)124)100-70(119)55(33-62(113)114)99-69(118)54(32-61(111)112)98-67(116)51(14-10-24-90-79(87)88)96-68(117)53(31-60(109)110)94-59(108)20-19-52(72(121)122)97-66(115)43-15-17-44(18-16-43)91-37-45-38-92-65-63(93-45)71(120)102-80(89)101-65/h8-9,11-13,15-18,22,30,34,38,42,51-56,74-76,91,95,125,129-130H,6-7,10,14,19-21,23-29,31-33,35-37,39-41H2,1-5H3,(H,94,108)(H,96,117)(H,97,115)(H,98,116)(H,99,118)(H,100,119)(H,103,126)(H,104,128)(H,109,110)(H,111,112)(H,113,114)(H,121,122)(H,123,124)(H4,87,88,90)(H3,89,92,101,102,120)/t42-,51-,52-,53-,54-,55-,56-,74-,75+,76+,82-,83+,84+,85-,86-/m0/s1
IUPAC Name
SMILES
[H][C@@]12N3CC[C@@]11C4=CC(=C(OC)C=C4N(C)[C@@]1([H])[C@](O)([[email protected]](O)[C@]2(CC)C=CC3)C(=O)NNC(=O)OCCSSC[[email protected]](NC(=O)[[email protected]](CC(O)=O)NC(=O)[[email protected]](CC(O)=O)NC(=O)[[email protected]](CCCNC(N)=N)NC(=O)[[email protected]](CC(O)=O)NC(=O)CC[[email protected]](NC(=O)C1=CC=C(NCC2=CNC3=NC(N)=NC(=O)C3=N2)C=C1)C(O)=O)C(O)=O)[C@]1(C[C@@]2([H])C[N@](C[C@](O)(CC)C2)CCC2=C1NC1=CC=CC=C21)C(=O)OC
Pharmacology
Indication

Investigated for use/treatment in solid tumors.

Structured Indications Not Available
PharmacodynamicsNot Available
Mechanism of action

Vintafolide minimizes the off-target toxicity by delivering the vinca molecule directly and specifically to cancer cells that over-express the folate-receptor. Once delivered to the cancer cell surface, Vintafolide is internalized into the cancer cell via endocytosis, a natural cellular process. Once inside the cell, Endocyte’s proprietary linker technology releases the chemotherapy to eliminate the cancer cell.

TargetKindPharmacological actionActionsOrganismUniProt ID
Folate receptor betaProteinunknownNot AvailableHumanP14207 details
Folate receptor gammaProteinunknownNot AvailableHumanP41439 details
Folate receptor alphaProteinunknownNot AvailableHumanP15328 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Leamon CP, Reddy JA, Vlahov IR, Westrick E, Parker N, Nicoson JS, Vetzel M: Comparative preclinical activity of the folate-targeted Vinca alkaloid conjugates EC140 and EC145. Int J Cancer. 2007 Oct 1;121(7):1585-92. [PubMed:17551919 ]
  2. Reddy JA, Dorton R, Westrick E, Dawson A, Smith T, Xu LC, Vetzel M, Kleindl P, Vlahov IR, Leamon CP: Preclinical evaluation of EC145, a folate-vinca alkaloid conjugate. Cancer Res. 2007 May 1;67(9):4434-42. [PubMed:17483358 ]
External Links
ATC CodesL01CA06 — Vintafolide
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentCancers1
1TerminatedTreatmentCancer, Advanced1
1TerminatedTreatmentTumors, Solid1
2Active Not RecruitingTreatmentTumors, Solid1
2CompletedTreatmentAdenocarcinoma of the Lung1
2CompletedTreatmentCancer, Ovarian1
2CompletedTreatmentCancer, Ovarian / Endometrial Cancers1
2CompletedTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
2WithdrawnTreatmentNeoplasms, Breast1
3SuspendedTreatmentCancer, Ovarian1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0133 mg/mLALOGPS
logP1.42ALOGPS
logS-5.2ALOGPS
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as vinca alkaloids. These are alkaloids with a dimeric chemical structure composed of an indole nucleus (catharanthine), and a dihydroindole nucleus (vindoline), joined together.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassVinca alkaloids
Sub ClassNot Available
Direct ParentVinca alkaloids
Alternative ParentsOligopeptides / Hexacarboxylic acids and derivatives / Arginine and derivatives / Glutamine and derivatives / Aspartic acid and derivatives / Carbazoles / Hippuric acids / N-acyl-L-alpha-amino acids / Quinoline carboxamides / Pterins and derivatives
SubstituentsVinca alkaloid skeleton / Alpha-oligopeptide / Hexacarboxylic acid or derivatives / Alpha peptide / Arginine or derivatives / Glutamine or derivatives / Aspartic acid or derivatives / Hippuric acid / Hippuric acid or derivatives / N-acyl-alpha amino acid or derivatives
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Methotrexate binding
Specific Function:
Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells. Has high affinity for folate and folic acid analogs at neutral pH. Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release.
Gene Name:
FOLR2
Uniprot ID:
P14207
Molecular Weight:
29279.31 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Folic acid binding
Specific Function:
Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate to the interior of cells. Isoform Short does not bind folate.
Gene Name:
FOLR3
Uniprot ID:
P41439
Molecular Weight:
27638.0 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Receptor activity
Specific Function:
Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells. Has high affinity for folate and folic acid analogs at neutral pH. Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release. Required for norma...
Gene Name:
FOLR1
Uniprot ID:
P15328
Molecular Weight:
29818.94 Da
Drug created on October 21, 2007 16:23 / Updated on June 11, 2017 21:00