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Identification
NameBiricodar dicitrate
Accession NumberDB04851
TypeSmall Molecule
GroupsInvestigational
DescriptionThe pipecolinate derivative biricodar (VX-710) is a clinically applicable modulator of P-glycoprotein (Pgp) and multidrug resistance protein (MRP-1).
Structure
Thumb
Synonyms
biricodar
External Identifiers
  • VX-710
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
IncelNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
UNII9WQP0L619L
CAS number174254-13-8
WeightAverage: 987.9523
Monoisotopic: 987.348455901
Chemical FormulaC46H57N3O21
InChI KeyInChIKey=VDMKJSJJXQDICL-ZXVJYWQYSA-N
InChI
InChI=1S/C34H41N3O7.2C6H8O7/c1-41-29-20-26(21-30(42-2)32(29)43-3)31(38)33(39)37-19-5-4-16-28(37)34(40)44-27(14-6-10-24-12-8-17-35-22-24)15-7-11-25-13-9-18-36-23-25;2*7-3(8)1-6(13,5(11)12)2-4(9)10/h8-9,12-13,17-18,20-23,27-28H,4-7,10-11,14-16,19H2,1-3H3;2*13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/t28-;;/m0../s1
IUPAC Name
1,7-bis(pyridin-3-yl)heptan-4-yl (2S)-1-[2-oxo-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate; bis(2-hydroxypropane-1,2,3-tricarboxylic acid)
SMILES
OC(=O)CC(O)(CC(O)=O)C(O)=O.OC(=O)CC(O)(CC(O)=O)C(O)=O.COC1=CC(=CC(OC)=C1OC)C(=O)C(=O)N1CCCC[[email protected]]1C(=O)OC(CCCC1=CN=CC=C1)CCCC1=CN=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid esters
Alternative Parents
Substituents
  • Alpha-amino acid ester
  • Phenylacetamide
  • Tricarboxylic acid or derivatives
  • Piperidinecarboxylic acid
  • N-acyl-piperidine
  • Acetophenone
  • Methoxybenzene
  • Aryl ketone
  • Phenol ether
  • Benzoyl
  • Anisole
  • Beta-hydroxy acid
  • Alkyl aryl ether
  • Benzenoid
  • Pyridine
  • Piperidine
  • Hydroxy acid
  • Monocyclic benzene moiety
  • Alpha-hydroxy acid
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Tertiary alcohol
  • Alpha-aminoketone
  • Tertiary amine
  • Ketone
  • Carboxylic acid ester
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteromonocyclic compound
  • Aliphatic acyclic compound
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationAdministered intravenously, biricodar dicitrate is to be used in combination with cancer chemotherapy agents.
PharmacodynamicsBiricodar dicitrate blocks two major multi-drug resistance mechanisms: P-glycoprotein (MDR-1) and multi-drug resistance-associated protein (MRP).
Mechanism of actionVertex’s research shows that biricodar dicitrate can enhance the accumulation of chemotherapy agents in tumor cells by blocking the drug pumps P-gp and MRP, and that it is capable of restoring the sensitivity of tumors to treatment with chemotherapeutic agents.
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 organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9372
Blood Brain Barrier-0.9496
Caco-2 permeable-0.6555
P-glycoprotein substrateSubstrate0.7999
P-glycoprotein inhibitor IInhibitor0.5124
P-glycoprotein inhibitor IINon-inhibitor0.5093
Renal organic cation transporterNon-inhibitor0.8498
CYP450 2C9 substrateNon-substrate0.7975
CYP450 2D6 substrateNon-substrate0.8208
CYP450 3A4 substrateSubstrate0.7234
CYP450 1A2 substrateNon-inhibitor0.8485
CYP450 2C9 inhibitorNon-inhibitor0.766
CYP450 2D6 inhibitorNon-inhibitor0.8887
CYP450 2C19 inhibitorNon-inhibitor0.8673
CYP450 3A4 inhibitorNon-inhibitor0.907
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9154
Ames testNon AMES toxic0.8794
CarcinogenicityNon-carcinogens0.9466
BiodegradationNot ready biodegradable0.9876
Rat acute toxicity2.6263 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9909
hERG inhibition (predictor II)Inhibitor0.5328
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
logP4.77ChemAxon
pKa (Strongest Basic)5.86ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area117.15 Å2ChemAxon
Rotatable Bond Count26ChemAxon
Refractivity164.5 m3·mol-1ChemAxon
Polarizability64.13 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Gandhi L, Harding MW, Neubauer M, Langer CJ, Moore M, Ross HJ, Johnson BE, Lynch TJ: A phase II study of the safety and efficacy of the multidrug resistance inhibitor VX-710 combined with doxorubicin and vincristine in patients with recurrent small cell lung cancer. Cancer. 2007 Mar 1;109(5):924-32. [PubMed:17285598 ]
  2. Mullin S, Mani N, Grossman TH: Inhibition of antibiotic efflux in bacteria by the novel multidrug resistance inhibitors biricodar (VX-710) and timcodar (VX-853). Antimicrob Agents Chemother. 2004 Nov;48(11):4171-6. [PubMed:15504837 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Efflux transmembrane transporter activity
Specific Function:
Drug efflux transporter present in a number of stem cells that acts as a regulator of cellular differentiation. Able to mediate efflux from cells of the rhodamine dye and of the therapeutic drug doxorubicin. Specifically present in limbal stem cells, where it plays a key role in corneal development and repair.
Gene Name:
ABCB5
Uniprot ID:
Q2M3G0
Molecular Weight:
138639.48 Da
References
  1. Minderman H, O'Loughlin KL, Pendyala L, Baer MR: VX-710 (biricodar) increases drug retention and enhances chemosensitivity in resistant cells overexpressing P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein. Clin Cancer Res. 2004 Mar 1;10(5):1826-34. [PubMed:15014037 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Transporter activity
Specific Function:
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.
Gene Name:
ABCC1
Uniprot ID:
P33527
Molecular Weight:
171589.5 Da
References
  1. Minderman H, O'Loughlin KL, Pendyala L, Baer MR: VX-710 (biricodar) increases drug retention and enhances chemosensitivity in resistant cells overexpressing P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein. Clin Cancer Res. 2004 Mar 1;10(5):1826-34. [PubMed:15014037 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. Minderman H, O'Loughlin KL, Pendyala L, Baer MR: VX-710 (biricodar) increases drug retention and enhances chemosensitivity in resistant cells overexpressing P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein. Clin Cancer Res. 2004 Mar 1;10(5):1826-34. [PubMed:15014037 ]
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Drug created on October 18, 2007 17:04 / Updated on August 17, 2016 12:24