Laniquidar

Laniquidar
Clinical data
ATC code
  • none
Identifiers
IUPAC name
  • methyl 11-(1-{2-[4-(quinolin-2-ylmethoxy)phenyl]ethyl}piperidin-4-ylidene)-6,11-dihydro-5H-imidazo[2,1-b][3]benzazepine-3-carboxylate
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC37H36N4O3
Molar mass584.720 g·mol−1
3D model (JSmol)
SMILES
  • COC(=O)C1=CN=C2N1CCC3=CC=CC=C3C2=C4CCN(CC4)CCC5=CC=C(C=C5)OCC6=NC7=CC=CC=C7C=C6
InChI
  • InChI=1S/C37H36N4O3/c1-43-37(42)34-24-38-36-35(32-8-4-2-6-27(32)19-23-41(34)36)29-17-21-40(22-18-29)20-16-26-10-14-31(15-11-26)44-25-30-13-12-28-7-3-5-9-33(28)39-30/h2-15,24H,16-23,25H2,1H3
  • Key:TULGGJGJQXESOO-UHFFFAOYSA-N
  (verify)

Laniquidar (INN) is a third generation P-glycoprotein inhibitor that underwent clinical studies for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).[1] It has been discontinued because of its low bioavailability and a high variability with how the patients responded to the drug.[2]

Clinical Trials

Laniquidar has been tested for its efficacy for treating refractory breast cancer together with docetaxel and paclitaxel. Phase 2 clinical trials began in September 2001 by the European Organization for Research and Treatment of Cancer (EORTC) which included 35 participants. These patients have not responded to prior chemotherapy treatments. The study ended in June 2002 but the results have not been reported.[3]

Chemistry

Laniquidar is a benzazepine. The chemical name for Laniquidar is methyl 11-(1-(4-quinolin-2-ylmethoxy)phenethyl)piperidin-4ylidene)-6,11-dihydro-5H-benzo[d]imidazo[1,2-a]azepine-3-carboxylate and its free base form has a chemical formula of C37H36N4O3 with a molecular weight of 584.720 g/mol.[4]

Mechanism of Action

Laniquidar is a highly selective P-Glycoprotein (P-gp) inhibitor that also has a high lipophilicity. P-gp is a mulit-drug resistant protein that causes the efflux of substrates such as chemotherapeutic drugs out of the cell. Laniquidar works to inhibit the efflux by causing a conformational change of P-gp. This hinders ATP hydrolysis and the substrate can not be positioned to leave the cell since the permeability of the cell membrane decreases.[5]

References

  1. ↑ Ross DD (December 2004). "Modulation of drug resistance transporters as a strategy for treating myelodysplastic syndrome". Best Practice & Research. Clinical Haematology. 17 (4): 641–51. doi:10.1016/j.beha.2004.08.014. PMID 15494300.
  2. ↑ Reina., Sosnik, Alejandro. Bendayan (2020). Drug efflux pumps in cancer resistance pathways : from molecular recognition and characterization to possible inhibition strategies in chemotherapy. Academic Press. ISBN 978-0-12-814141-0. OCLC 1127254794.
  3. ↑ "R101933 Combined With Chemotherapy in Treating Patients With Metastatic Breast Cancer That Has Not Responded to Previous Chemotherapy - Tabular View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2021-04-29.
  4. ↑ PubChem. "Laniquidar". pubchem.ncbi.nlm.nih.gov. Retrieved 2021-04-29.
  5. ↑ "Seminars in radiation oncology". Nuclear Medicine and Biology. 30 (3): I–II. April 2003. doi:10.1016/s0969-8051(03)00045-3. ISSN 0969-8051.


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