| Identification | Back Directory | [Name]
1,4-Butanediamine, N1-[[4-[[(1H-imidazol-2-ylmethyl)[(1-methyl-1H-imidazol-2-yl)methyl]amino]methyl]phenyl]methyl]-N1-methyl-N4,N4-dipropyl-, hydrochloride (1:3) | [CAS]
2253744-59-9 | [Synonyms]
1,4-Butanediamine, N1-[[4-[[(1H-imidazol-2-ylmethyl)[(1-methyl-1H-imidazol-2-yl)methyl]amino]methyl]phenyl]methyl]-N1-methyl-N4,N4-dipropyl-, hydrochloride (1:3) | [Molecular Formula]
C28H46ClN7 | [MOL File]
2253744-59-9.mol | [Molecular Weight]
516.18 |
| Hazard Information | Back Directory | [Uses]
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]. | [Biological Activity]
KRH 3955 hydrochloride is a highly potent CXCR4 antagonist (IC50 = 0.61 nM). Displays selectivity for CXCR4 over a range of other CXC receptors. Inhibits replication of HIV-1 viruses in human PBMC (EC50 values are 0.33 to 1.4 nM). Supresses HIV-1 infection in mice. Orally bioavailable. | [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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| [IC 50]
SDF-1α-CXCR4: 0.61 nM (IC50); X4 HIV-1NL4-3: 0.3-1.0 nM (EC50) | [storage]
Desiccate at RT | [References]
[1] Tsutomu M, et, al. The Novel CXCR4 Antagonist KRH-3955 Is an Orally Bioavailable and Extremely Potent Inhibitor of Human Immunodeficiency Virus Type 1 Infection: Comparative Studies With AMD3100. Antimicrob Agents Chemother. 2009 Jul; 53(7): 2940-8. DOI:10.1128/AAC.01727-08 |
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