Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A series of trans-3-oxospiro[(aza)isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide derivatives were synthesized and profiled for
NPY
Y5 binding affinity, brain and CSF penetrability in rats, and susceptibility to human and mouse
P-glycoprotein
transporters in order to develop a PET ligand. Compound 12b exhibited an acceptable profile for a PET ligand, and [(11)C]12b was successfully utilized in clinical settings as a Y5 PET ligand.
...
PMID:Identification of positron emission tomography ligands for NPY Y5 receptors in the brain. 1967 69
A series of trans-3-oxospiro[(aza)isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide derivatives were synthesized to identify potent
NPY
Y5 receptor antagonists. Of the compounds, 21j showed high Y5 binding affinity, metabolic stability and brain and cerebrospinal fluid (CSF) penetration, and low susceptibility to
P-glycoprotein
transporters. Oral administration of 21j significantly inhibited the Y5 agonist-induced food intake in rats with a minimum effective dose of 1mg/kg. This compound was selected for proof-of-concept studies in human clinical trials.
...
PMID:Discovery of trans-N-[1-(2-fluorophenyl)-3-pyrazolyl]-3-oxospiro[6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide, a potent and orally active neuropeptide Y Y5 receptor antagonist. 1972 May 39
Multidrug resistance (MDR) is one of the main reasons for the inefficiency of cancer chemotherapy. As a consequence of MDR, the expression level of membrane proteins might be changed, which can thus be used to develop a novel strategy for its treatment. Based on the high overexpression of Y
1
receptor (Y
1
R) protein and
P-glycoprotein
(
P-gp
) in the multidrug resistant breast cancer cell line, a selective Y
1
R ligand [Asn
6
, Pro
34
]-
NPY
(AP) was employed to stabilize the chemotherapeutic drug doxorubicin (DOX) and
P-gp
inhibitor tariquidar (Tar) co-loaded nanomicelles at the physiological level. This also improved the targeted delivery of DOX and Tar into MCF-7/ADR cells. Co-delivered Tar further impedes the efflux of DOX and enhances its accumulation in the nuclei of drug resistant cancer cells, thereby inducing significant inhibition of cell growth. The synergistic effect of AP and Tar generates an excellent in vivo tumor targeting and antitumor efficacy of DOX with prolonged survival and minimized side effects, especially for liver metastasis. In general, Y
1
R as a novel target site and its selective ligand AP synergized with the
P-gp
inhibitor can be used for a more precise MDR breast cancer treatment.
...
PMID:A Y
1
receptor ligand synergized with a P-glycoprotein inhibitor improves the therapeutic efficacy of multidrug resistant breast cancer. 3150 13
