Biricodar

Identification

Generic Name
Biricodar
DrugBank Accession Number
DB04851
Background

The pipecolinate derivative biricodar (VX-710) is a clinically applicable modulator of P-glycoprotein (Pgp) and multidrug resistance protein (MRP-1).

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 603.716
Monoisotopic: 603.294450672
Chemical Formula
C34H41N3O7
Synonyms
  • Biricodar
External IDs
  • VX 710
  • VX-710

Pharmacology

Indication

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

Reduce drug development failure rates
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Contraindications & Blackbox Warnings
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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 AvailableHumans
UMultidrug resistance-associated protein 1Not AvailableHumans
UATP-binding cassette sub-family G member 2Not AvailableHumans
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

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Biricodar.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Biricodar.
AmbrisentanThe serum concentration of Ambrisentan can be increased when it is combined with Biricodar.
ApixabanThe serum concentration of Apixaban can be increased when it is combined with Biricodar.
AvanafilThe serum concentration of Avanafil can be increased when it is combined with Biricodar.
Food Interactions
Not Available

Products

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Product Ingredients
IngredientUNIICASInChI Key
Biricodar dicitrate9WQP0L619L174254-13-8VDMKJSJJXQDICL-ZXVJYWQYSA-N
International/Other Brands
Incel

Categories

Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
3KG76X4KJK
CAS number
159997-94-1
InChI Key
CGVWPQOFHSAKRR-NDEPHWFRSA-N
InChI
InChI=1S/C34H41N3O7/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/h8-9,12-13,17-18,20-23,27-28H,4-7,10-11,14-16,19H2,1-3H3/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
SMILES
COC1=CC(=CC(OC)=C1OC)C(=O)C(=O)N1CCCC[C@H]1C(=O)OC(CCCC1=CN=CC=C1)CCCC1=CN=CC=C1

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. [Article]
  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. [Article]
KEGG Drug
D03128
PubChem Compound
9963148
PubChem Substance
175426862
ChemSpider
2301309
BindingDB
50109811
ChEBI
135847
ChEMBL
CHEMBL350775
PharmGKB
PA164924560
Wikipedia
Biricodar

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2TerminatedTreatmentLung Cancer1

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 Solubility0.00129 mg/mLALOGPS
logP4.54ALOGPS
logP4.77Chemaxon
logS-5.7ALOGPS
pKa (Strongest Basic)5.86Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area117.15 Å2Chemaxon
Rotatable Bond Count16Chemaxon
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/MSsplash10-00di-0391111000-340079a2b066d39c9081
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-0309100000-71a7dd192dfe2a9bfa02
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0zmi-1955323000-933e8600867b8c49f422
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0529010000-827ca1d383456b0f4c95
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-1039-2973341000-a9b0f9c083eb98f55674
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0pdi-2936641000-f8fd2bda102396376eb0
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

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Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. NCI Dictionary: Biricodar [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Modulator
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. Grzywacz MJ, Yang JM, Hait WN: Effect of the multidrug resistance protein on the transport of the antiandrogen flutamide. Cancer Res. 2003 May 15;63(10):2492-8. [Article]

Drug created at October 18, 2007 23:04 / Updated at June 17, 2022 22:04