Encequidar

Research use only, not for human use.

Encequidar is a potent and selective P-glycoprotein inhibitor. HM30181 to inhibit Pgp at the murine BBB.

Encequidar is a potent and selective P-glycoprotein inhibitor. HM30181 to inhibit Pgp at the murine BBB.?HM30181 was shown to be approximately equipotent with the reference Pgp inhibitor tariquidar in inhibiting rhodamine 123 efflux from CCRF-CEM T cells (IC(50), tariquidar: 8.2 2.0 nM, HM30181: 13.1 2.3 nM).?PET scans with the Pgp substrate (R)-[(11)C]verapamil in FVB wild-type mice pretreated i.v. with HM30181 (10 or 21 mg/kg) failed to show significant increases in (R)-[(11)C]verapamil brain uptake compared with vehicle treated animals.?PET scans with [(11)C]HM30181 showed low and not significantly different brain uptake of [(11)C]HM30181 in wild-type, Mdr1a/b((-/-)) and Bcrp1((-/-)) mice and significantly, i.e. 4.7-fold (P<0.01), higher brain uptake, relative to wild-type animals, in Mdr1a/b((-/-))Bcrp1((-/-)) mice.(In Vitro):Encequidar (HM30181; HM30181A) is shown to be approximately equipotent with the reference Pgp inhibitor tariquidar in inhibiting rhodamine 123 efflux from CCRF-CEM T cells (IC50, tariquidar: 8.2±2.0 nM, Encequidar (HM30181): 13.1±2.3 nM) .Encequidar (HM30181) shows a high selectivity for mP-gp and its potency is 20-50 times higher than that of tariquitar, another third generation P-gp inhibitor.(In Vivo):PET scans with the Pgp substrate (R)-[11C]NSC 657799 in FVB wild-type mice pretreated i.v. with Encequidar (HM30181) (10 or 21 mg/kg) failes to show significant increases in (R)-[11C]NSC 657799 brain uptake compared with vehicle treated animals.Encequidar (HM30181) inhibits P-gp mainly in the intestinal endothelium, which can be beneficial because pan-inhibition of P-gp, particularly in the brain, could lead to detrimental adverse events. Encequidar (HM30181) increases the oral bioavailability of co-administered NSC 125973 by more than 12 times in rats.

Encequidar (HM30181; HM30181A) is shown to be approximately equipotent with the reference Pgp inhibitor tariquidar in inhibiting rhodamine 123 efflux from CCRF-CEM T cells (IC50, tariquidar: 8.2±2.0 nM, Encequidar (HM30181): 13.1±2.3 nM) . Encequidar (HM30181) shows a high selectivity for mP-gp and its potency is 20-50 times higher than that of tariquitar, another third generation P-gp inhibitor.

PET scans with the Pgp substrate (R)-[11C]NSC 657799 in FVB wild-type mice pretreated i.v. with Encequidar (HM30181) (10 or 21 mg/kg) failes to show significant increases in (R)-[11C]NSC 657799 brain uptake compared with vehicle treated animals. Encequidar (HM30181) inhibits P-gp mainly in the intestinal endothelium, which can be beneficial because pan-inhibition of P-gp, particularly in the brain, could lead to detrimental adverse events. Encequidar (HM30181) increases the oral bioavailability of co-administered NSC 125973 by more than 12 times in rats.

HM30181,HM30181A

Others

Other Targets

P-gp?(P-glycoprotein)

Cancer

Advanced Solid Malignancies

849675-66-7

688.73

C38H36N6O7

>98% (HPLC)

DMSO:6.9 mg/mL (10.02 mM; Need ultrasonic)

COc1cc2CCN(CCc3ccc(cc3)-n3nnc(n3)-c3cc(OC)c(OC)cc3NC(=O)c3cc(=O)c4ccccc4o3)Cc2cc1OC

——

(-20℃)

With Ice Pack

≥ 2 years