产品
编 号：F715273
分子式：C28H48Cl3N7
分子量：589.09
分子式：C28H48Cl3N7
分子量：589.09
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CAS No: 2253744-59-9
产品详情
生物活性：
KRH-3955 hydrochloride is an orally bioavailable CXCR4 antagonist. KRH-3955 hydrochloride inhibits SDF-1α binding to CXCR4 with an IC50 of 0.61 nM. KRH-3955 hydrochloride is also a highly potent and selective inhibitor of X4 HIV-1, with an EC50 of 0.3 to 1.0 nM.
体内研究：
KRH-3955(10 mg/kg; a single p.o.) efficiently suppresses X4 HIV-1 infection in hu-PBL-SCID mice.KRH-3955 (10 mg/kg; a single p.o.) exhibits moderate oral bioavailability (25.6%) and Cmax (86.3 ng/mL).KRH-3955 (10 mg/kg; a single i.v.) exhibits terminal elimination half-lives (99 h) due to high plasma clearance (3.9 liters/h/kg) combined with large volumes of distribution (374 liters/kg).Animal Model:C.B-17 SCID mice engrafted with human PBMCs and injected with infectious X4 HIV-1 (NL4-3)
Dosage:10 mg/kg
Administration:A single p.o. administration
Result:Four of five mock-treated mice were infected whereas only one of five mice treated with KRH-3955 was infected.
Animal Model:Male Sprague-Dawley rats
Dosage:10 mg/kg (Pharmacokinetic Analysis)
Administration:A single p.o. or i.v. administration
Result:Well absorbed and the absolute oral bioavailability in rats was calculated to be 25.6%.The half time (T1/2) of 99.0±13.1 h.Stable in human hepatic microsomes, and no significant inhibition of CYP450 liver enzymes by this compound was observed.
体外研究：
KRH-3955 inhibits the replication of NL4-3 in activated peripheral blood mononuclear cells (PBMCs) from eight different donors with the EC50 ranging from 0.23 to 1.3 nM.KRH-3955 inhibits the infection of CD4/CXCR4 cells by these recombinant drug-resistant viruses, including viruses resistant to PIs, NRTIs, or NNRTIs, multidrug-resistant viruses and T20-resistant viruses, with the IC50 ranging from 0.4 to 0.8 nM.KRH-3955 (10-100 nM) inhibits the SDF-1α-induced increase in the intracellular Ca2+ concentration in a dose-dependent manner.KRH-3955 (0.1-1000 nM) binding sites are located in a region composed of all three extracellular loops (ECLs) of CXCR4.KRH-3955 (10 nM) has a strong binding affinity for CXCR4 and a slow dissociation rate.KRH-3955 inhibits MAb 12G5 binding to CXCR4 mutants, with the IC50 ranging from 0.5 to 14.1 nM.
KRH-3955 hydrochloride is an orally bioavailable CXCR4 antagonist. KRH-3955 hydrochloride inhibits SDF-1α binding to CXCR4 with an IC50 of 0.61 nM. KRH-3955 hydrochloride is also a highly potent and selective inhibitor of X4 HIV-1, with an EC50 of 0.3 to 1.0 nM.
体内研究：
KRH-3955(10 mg/kg; a single p.o.) efficiently suppresses X4 HIV-1 infection in hu-PBL-SCID mice.KRH-3955 (10 mg/kg; a single p.o.) exhibits moderate oral bioavailability (25.6%) and Cmax (86.3 ng/mL).KRH-3955 (10 mg/kg; a single i.v.) exhibits terminal elimination half-lives (99 h) due to high plasma clearance (3.9 liters/h/kg) combined with large volumes of distribution (374 liters/kg).Animal Model:C.B-17 SCID mice engrafted with human PBMCs and injected with infectious X4 HIV-1 (NL4-3)
Dosage:10 mg/kg
Administration:A single p.o. administration
Result:Four of five mock-treated mice were infected whereas only one of five mice treated with KRH-3955 was infected.
Animal Model:Male Sprague-Dawley rats
Dosage:10 mg/kg (Pharmacokinetic Analysis)
Administration:A single p.o. or i.v. administration
Result:Well absorbed and the absolute oral bioavailability in rats was calculated to be 25.6%.The half time (T1/2) of 99.0±13.1 h.Stable in human hepatic microsomes, and no significant inhibition of CYP450 liver enzymes by this compound was observed.
体外研究：
KRH-3955 inhibits the replication of NL4-3 in activated peripheral blood mononuclear cells (PBMCs) from eight different donors with the EC50 ranging from 0.23 to 1.3 nM.KRH-3955 inhibits the infection of CD4/CXCR4 cells by these recombinant drug-resistant viruses, including viruses resistant to PIs, NRTIs, or NNRTIs, multidrug-resistant viruses and T20-resistant viruses, with the IC50 ranging from 0.4 to 0.8 nM.KRH-3955 (10-100 nM) inhibits the SDF-1α-induced increase in the intracellular Ca2+ concentration in a dose-dependent manner.KRH-3955 (0.1-1000 nM) binding sites are located in a region composed of all three extracellular loops (ECLs) of CXCR4.KRH-3955 (10 nM) has a strong binding affinity for CXCR4 and a slow dissociation rate.KRH-3955 inhibits MAb 12G5 binding to CXCR4 mutants, with the IC50 ranging from 0.5 to 14.1 nM.
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