This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Zosuquidar
Accession Number
DB06191
Description

Zosuquidar is a compound of antineoplastic drug candidates currently under development. It is now in "Phase 3" of clinical tests in the United States. Its action mechanism consists of the inhibition of P-glycoproteins; other drugs with this mechanism include tariquidar and laniquidar.

Type
Small Molecule
Groups
Investigational
Structure
Thumb
Weight
Average: 527.616
Monoisotopic: 527.238433576
Chemical Formula
C32H31F2N3O2
Synonyms
Not Available

Pharmacology

Indication

Investigated for use/treatment in leukemia (myeloid) and myelodysplastic syndrome.

Contraindications & Blackbox Warnings
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Pharmacodynamics
Not Available
Mechanism of action

P-glycoproteins are proteins which convert the energy derived from the hydrolysis of ATP to structural changes in protein molecules, in order to perform coupling, thus discharging medicine from cells. If P-glycoprotein coded with the MDR1 gene manifests itself in cancer cells, it discharges much of the antineoplastic drugs from the cells, making cancer cells medicine tolerant, and rendering antineoplastic drugs ineffective. This protein also manifests itself in normal organs not affected by the cancer (such as the liver, small intestine, and skin cells in blood vessels of the brain), and participates in the transportation of medicine. The compound Zosuquidar inhibits this P-glycoprotein, causing the cancer cells to lose their medicine tolerance, and making antineoplastic drugs effective.

TargetActionsOrganism
AP-glycoprotein 1
inhibitor
Humans
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
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
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
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Zosuquidar.
AmbrisentanThe serum concentration of Ambrisentan can be increased when it is combined with Zosuquidar.
ApixabanThe serum concentration of Apixaban can be increased when it is combined with Zosuquidar.
AvatrombopagThe serum concentration of Avatrombopag can be increased when it is combined with Zosuquidar.
BaricitinibThe serum concentration of Baricitinib can be increased when it is combined with Zosuquidar.
BelinostatThe serum concentration of Belinostat can be increased when it is combined with Zosuquidar.
BendamustineThe serum concentration of Bendamustine can be increased when it is combined with Zosuquidar.
BetrixabanThe serum concentration of Betrixaban can be increased when it is combined with Zosuquidar.
BinimetinibThe serum concentration of Binimetinib can be increased when it is combined with Zosuquidar.
BisoprololThe serum concentration of Bisoprolol can be increased when it is combined with Zosuquidar.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

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Food Interactions
Not Available

Products

Product Ingredients
IngredientUNIICASInChI Key
Zosuquidar trihydrochloride813AGY3126167465-36-3ZPFVQKPWGDRLHL-WITOOOCMSA-N

Categories

Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
AB5K82X98Y
CAS number
167354-41-8
InChI Key
IHOVFYSQUDPMCN-DBEBIPAYSA-N
InChI
InChI=1S/C32H31F2N3O2/c33-32(34)29-22-7-1-3-9-24(22)31(25-10-4-2-8-23(25)30(29)32)37-17-15-36(16-18-37)19-21(38)20-39-28-13-5-12-27-26(28)11-6-14-35-27/h1-14,21,29-31,38H,15-20H2/t21-,29-,30+,31-/m1/s1
IUPAC Name
(2R)-1-{4-[(2R,4S,11R)-3,3-difluorotetracyclo[10.4.0.0^{2,4}.0^{5,10}]hexadeca-1(16),5,7,9,12,14-hexaen-11-yl]piperazin-1-yl}-3-(quinolin-5-yloxy)propan-2-ol
SMILES
[H][[email protected]]12C3=CC=CC=C3[[email protected]](N3CCN(C[[email protected]@H](O)COC4=CC=CC5=C4C=CC=N5)CC3)C3=CC=CC=C3[[email protected]@]1([H])C2(F)F

References

General References
Not Available
PubChem Compound
153997
ChemSpider
24599682
BindingDB
50420186
ChEMBL
CHEMBL444172
ZINC
ZINC000100029945
PDBe Ligand
ZQU
Wikipedia
Zosuquidar
PDB Entries
6fn1 / 6qee / 7a6f

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentLeukemias / Myelodysplastic Syndromes (MDS)1
1, 2CompletedTreatmentMyeloid Leukemias2

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 Solubility0.00974 mg/mLALOGPS
logP5.17ALOGPS
logP4.82ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)14.08ChemAxon
pKa (Strongest Basic)7.63ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area48.83 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity146.68 m3·mol-1ChemAxon
Polarizability56.04 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.8998
Blood Brain Barrier+0.9118
Caco-2 permeable-0.6096
P-glycoprotein substrateSubstrate0.8405
P-glycoprotein inhibitor IInhibitor0.8163
P-glycoprotein inhibitor IIInhibitor0.9785
Renal organic cation transporterNon-inhibitor0.51
CYP450 2C9 substrateNon-substrate0.7839
CYP450 2D6 substrateNon-substrate0.6365
CYP450 3A4 substrateSubstrate0.5488
CYP450 1A2 substrateInhibitor0.6444
CYP450 2C9 inhibitorNon-inhibitor0.6474
CYP450 2D6 inhibitorInhibitor0.5249
CYP450 2C19 inhibitorNon-inhibitor0.6238
CYP450 3A4 inhibitorNon-inhibitor0.7309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7929
Ames testNon AMES toxic0.638
CarcinogenicityNon-carcinogens0.9009
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7076 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8796
hERG inhibition (predictor II)Inhibitor0.9373
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
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. Nies AT, Herrmann E, Brom M, Keppler D: Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). Naunyn Schmiedebergs Arch Pharmacol. 2008 Feb;376(6):449-61. Epub 2007 Dec 19. [PubMed:18157518]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Yes
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. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]

Drug created on March 19, 2008 10:16 / Updated on July 02, 2020 07:24

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