Biricodar dicitrate

Identification

Name
Biricodar dicitrate
Accession Number
DB04851
Type
Small Molecule
Groups
Investigational
Description

The 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 IDs
VX-710 / VX-710-3
International/Other Brands
Incel
Categories
Not Available
UNII
9WQP0L619L
CAS number
174254-13-8
Weight
Average: 987.9523
Monoisotopic: 987.348455901
Chemical Formula
C46H57N3O21
InChI Key
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

Pharmacology

Indication

Administered intravenously, biricodar dicitrate is to be used in combination with cancer chemotherapy agents.

Structured Indications
Not Available
Pharmacodynamics

Biricodar dicitrate blocks two major multi-drug resistance mechanisms: P-glycoprotein (MDR-1) and multi-drug resistance-associated protein (MRP).

Mechanism of action

Vertex’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.

TargetActionsOrganism
UATP-binding cassette sub-family B member 5Not AvailableHuman
UMultidrug resistance-associated protein 1Not AvailableHuman
UATP-binding cassette sub-family G member 2Not 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
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

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
KEGG Drug
D03128
PubChem Compound
9963148
PubChem Substance
175426862
ChemSpider
8138745
ChEMBL
CHEMBL2104406

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2TerminatedTreatmentLung Cancers1

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
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid esters
Alternative Parents
Phenylacetamides / Tricarboxylic acids and derivatives / N-acylpiperidines / Piperidinecarboxylic acids / Anisoles / Aryl ketones / Benzoyl derivatives / Methoxybenzenes / Phenoxy compounds / Alkyl aryl ethers
show 9 more
Substituents
Alpha-amino acid ester / Phenylacetamide / N-acyl-piperidine / Piperidinecarboxylic acid / Tricarboxylic acid or derivatives / Phenoxy compound / Anisole / Benzoyl / Phenol ether / Methoxybenzene
show 23 more
Molecular Framework
Not Available
External Descriptors
Not 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 do...
Gene Name
ABCB5
Uniprot ID
Q2M3G0
Uniprot Name
ATP-binding cassette sub-family B member 5
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, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
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 fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
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]

Drug created on October 18, 2007 17:04 / Updated on November 09, 2017 03:48