Vintafolide

Identification

Name
Vintafolide
Accession Number
DB05168  (DB12503)
Type
Small Molecule
Groups
Investigational
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
Synonyms
Not Available
External IDs
EC-145 / EC145
Categories
UNII
36O410ZD4I
CAS number
742092-03-1
Weight
Average: 1917.06
Monoisotopic: 1915.729405062
Chemical Formula
C86H109N21O26S2
InChI Key
KUZYSQSABONDME-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
(2S)-2-[(4-{[(2-amino-4-oxo-4,8-dihydropteridin-6-yl)methyl]amino}phenyl)formamido]-4-{[(1S)-1-{[(1S)-4-carbamimidamido-1-{[(1S)-2-carboxy-1-{[(1S)-2-carboxy-1-{[(1R)-1-carboxy-2-{[2-({N'-[(1R,9R,10S,11R,12R,19R)-12-ethyl-4-[(1R,13S,15R,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0^{4,12}.0^{5,10}]nonadeca-4(12),5,7,9-tetraen-13-yl]-10,11-dihydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.0^{1,9}.0^{2,7}.0^{16,19}]nonadeca-2,4,6,13-tetraene-10-carbonyl]hydrazinecarbonyl}oxy)ethyl]disulfanyl}ethyl]carbamoyl}ethyl]carbamoyl}ethyl]carbamoyl}butyl]carbamoyl}-2-carboxyethyl]carbamoyl}butanoic acid
SMILES
[H][[email protected]@]12N3CC[[email protected]@]11C4=CC(=C(OC)C=C4N(C)[[email protected]@]1([H])[[email protected]](O)([[email protected]](O)[[email protected]]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)[[email protected]]1(C[[email protected]@]2([H])C[[email protected]](C[[email protected]](O)(CC)C2)CCC2=C1NC1=CC=CC=C21)C(=O)OC

Pharmacology

Indication

Investigated for use/treatment in solid tumors.

Structured Indications
Not Available
Pharmacodynamics
Not 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.

TargetActionsOrganism
UFolate receptor betaNot AvailableHuman
UFolate receptor gammaNot AvailableHuman
UFolate receptor alphaNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Vintafolide.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Vintafolide.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Vintafolide.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Vintafolide.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Vintafolide.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Vintafolide.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Vintafolide.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Vintafolide.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Vintafolide.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Vintafolide.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Vintafolide.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Vintafolide.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Vintafolide.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Vintafolide.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Vintafolide.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Vintafolide.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Vintafolide.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Vintafolide.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Vintafolide.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Vintafolide.Approved, Investigational
Food Interactions
Not Available

References

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
PubChem Compound
122173811
PubChem Substance
347827715
ChemSpider
27444385
ChEBI
134736
ChEMBL
CHEMBL3039521
Wikipedia
EC145
ATC Codes
L01CA06 — Vintafolide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentCancers1
1TerminatedTreatmentCancer, Advanced1
1TerminatedTreatmentTumors, Solid1
2CompletedTreatmentAdenocarcinoma of the Lung1
2CompletedTreatmentCancer, Ovarian1
2CompletedTreatmentCancer, Ovarian / Endometrial Cancers1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2CompletedTreatmentTumors, Solid1
2WithdrawnTreatmentNeoplasms, Breast1
3SuspendedTreatmentCancer, Ovarian1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0133 mg/mLALOGPS
logP1.42ALOGPS
logP-12ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)2.47ChemAxon
pKa (Strongest Basic)11.9ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count36ChemAxon
Hydrogen Donor Count23ChemAxon
Polar Surface Area716.39 Å2ChemAxon
Rotatable Bond Count44ChemAxon
Refractivity492.22 m3·mol-1ChemAxon
Polarizability192.53 Å3ChemAxon
Number of Rings12ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Vinca alkaloids
Sub Class
Not Available
Direct Parent
Vinca alkaloids
Alternative Parents
Oligopeptides / 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
show 43 more
Substituents
Vinca 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
show 81 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not 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 analo...
Gene Name
FOLR2
Uniprot ID
P14207
Uniprot Name
Folate receptor beta
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
Uniprot Name
Folate receptor gamma
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 analo...
Gene Name
FOLR1
Uniprot ID
P15328
Uniprot Name
Folate receptor alpha
Molecular Weight
29818.94 Da

Drug created on October 21, 2007 16:23 / Updated on November 09, 2017 03:50