2253744-59-9
2253744-59-9 structure
- Name: KRH-3955 hydrochloride
- Chemical Name: KRH-3955 hydrochloride
- CAS Number: 2253744-59-9
- Molecular Formula: C28H48Cl3N7
- Molecular Weight: 589.09
- Catalog: Signaling Pathways Anti-infection HIV
- Create Date: 2020-08-08 13:44:42
- Modify Date: 2024-01-11 17:02:16
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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[1].
| Name | KRH-3955 hydrochloride |
|---|
| Description | 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[1]. |
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| Related Catalog | |
| Target |
SDF-1α-CXCR4:0.61 nM (IC50) X4 HIV-1NL4-3:0.3-1.0 nM (EC50) |
| In Vitro | 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[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 IC50 ranging 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 IC50 ranging from 0.5 to 14.1 nM[1]. |
| 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. |
| References |
| Molecular Formula | C28H48Cl3N7 |
|---|---|
| Molecular Weight | 589.09 |