KRH-3955 hydrochloride 是一种具有口服活性的CXCR4拮抗剂。KRH-3955 hydrochloride 抑制 SDF-1α 与CXCR4的结合，IC50为0.61 nM。KRH-3955 hydrochloride 也是高效的、选择性的X4 HIV-1抑制剂，EC50为 0.3 至 1.0 nM。
| 生物活性 | KRH-3955 hydrochloride is an orally bioavailableCXCR4antagonist. KRH-3955 hydrochloride inhibits SDF-1α binding toCXCR4with anIC50of 0.61 nM. KRH-3955 hydrochloride is also a highly potent and selective inhibitor ofX4HIV-1, with anEC50of 0.3 to 1.0 nM[1]. |
| IC50& Target[1] | X4 HIV-1NL4-3 0.3-1.0 nM (EC50) | SDF-1α-CXCR4 0.61 nM (IC50) |
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体外研究
(In Vitro) | KRH-3955 inhibits the replication of NL4-3 in activated peripheral blood mononuclear cells (PBMCs) from eight different donors with the EC50ranging from 0.23 to 1.3 nM[1].
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 IC50ranging from 0.4 to 0.8 nM[1].
KRH-3955 (10-100 nM) inhibits the SDF-1α-induced increase in the intracellular Ca2+concentration in a dose-dependent manner[1].
KRH-3955 (0.1-1000 nM) binding sites are located in a region composed of all three extracellular loops (ECLs) of CXCR4[1].
KRH-3955 (10 nM) has a strong binding affinity for CXCR4 and a slow dissociation rate[1].
KRH-3955 inhibits MAb 12G5 binding to CXCR4 mutants, with the IC50ranging from 0.5 to 14.1 nM[1].
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体内研究
(In Vivo) | KRH-3955 (10 mg/kg; a single p.o.) efficiently suppresses X4 HIV-1 infection in hu-PBL-SCID mice[1].
KRH-3955 (10 mg/kg; a single p.o.) exhibits moderate oral bioavailability (25.6%) and Cmax(86.3 ng/mL)[1].
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)[1].
| Animal Model: | C.B-17 SCID mice engrafted with human PBMCs and injected with infectious X4 HIV-1 (NL4-3)[1] | | 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[1] | | 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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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