Zosuquidar
Identification
- Generic Name
- Zosuquidar
- DrugBank Accession Number
- DB06191
- Background
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
- Weight
- Average: 527.616
Monoisotopic: 527.238433576 - Chemical Formula
- C32H31F2N3O2
- Synonyms
- Zosuquidar
Pharmacology
- Indication
Investigated for use/treatment in leukemia (myeloid) and myelodysplastic syndrome.
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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.
Target Actions Organism AP-glycoprotein 1 inhibitorHumans - 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Zosuquidar. Afatinib The serum concentration of Afatinib can be increased when it is combined with Zosuquidar. Ambrisentan The serum concentration of Ambrisentan can be increased when it is combined with Zosuquidar. Apixaban The serum concentration of Apixaban can be increased when it is combined with Zosuquidar. Avanafil The serum concentration of Avanafil can be increased when it is combined with Zosuquidar. - Food Interactions
- Not Available
Products
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- Product Ingredients
Ingredient UNII CAS InChI Key Zosuquidar trihydrochloride 813AGY3126 167465-36-3 ZPFVQKPWGDRLHL-WITOOOCMSA-N
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
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][C@]12C3=CC=CC=C3[C@H](N3CCN(C[C@@H](O)COC4=CC=CC5=C4C=CC=N5)CC3)C3=CC=CC=C3[C@@]1([H])C2(F)F
References
- General References
- Not Available
- External Links
- 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
Phase Status Purpose Conditions Count 3 Completed Treatment Leukemias / Myelodysplastic Syndrome 1 1, 2 Completed Treatment Myeloid Leukemias 2
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
Property Value Source Water Solubility 0.00974 mg/mL ALOGPS logP 5.17 ALOGPS logP 4.82 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 14.08 Chemaxon pKa (Strongest Basic) 7.63 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 48.83 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 146.68 m3·mol-1 Chemaxon Polarizability 56.04 Å3 Chemaxon Number of Rings 7 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8998 Blood Brain Barrier + 0.9118 Caco-2 permeable - 0.6096 P-glycoprotein substrate Substrate 0.8405 P-glycoprotein inhibitor I Inhibitor 0.8163 P-glycoprotein inhibitor II Inhibitor 0.9785 Renal organic cation transporter Non-inhibitor 0.51 CYP450 2C9 substrate Non-substrate 0.7839 CYP450 2D6 substrate Non-substrate 0.6365 CYP450 3A4 substrate Substrate 0.5488 CYP450 1A2 substrate Inhibitor 0.6444 CYP450 2C9 inhibitor Non-inhibitor 0.6474 CYP450 2D6 inhibitor Inhibitor 0.5249 CYP450 2C19 inhibitor Non-inhibitor 0.6238 CYP450 3A4 inhibitor Non-inhibitor 0.7309 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7929 Ames test Non AMES toxic 0.638 Carcinogenicity Non-carcinogens 0.9009 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.7076 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8796 hERG inhibition (predictor II) Inhibitor 0.9373
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
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
- 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. [Article]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Drug created at March 19, 2008 16:16 / Updated at March 03, 2024 02:32