x4-tropic

HIV-1 inhibitor-6 (3-Pyridinecarboxamide, 1,4-dihydro-1-methyl-N-(5-nitro-1,2-benzisothiazol-3-yl)-4-oxo-) 是一种有效的HIV-1 pre-mRNA 选择性剪接抑制剂，可以阻断HIV 复制。

GSK812397 is a potent entry inhibitor of X4-tropic strains of HIV-1, as demonstrated in multiple in vitro cellular assays. GSK812397 is a noncompetitive antagonist of the CXCR4 receptor, with GSK812397 producing a concentration-dependent decrease in both an SDF-1-mediated chemotaxis and intracellular calcium release (IC50s were 0.34+ -0.01 nM and 2.41+ -0.50 nM, respectively). GSK812397 is effective against a broad range of X4- and X4R5-utilizing clinical isolates. The potency and efficacy of GSK812397 are dependent on the individual isolate, with complete inhibition of infection observed with 24 of 30 isolates. GSK812397 does not show any detectable in vitro cytotoxicity and was highly selective for CXCR4. GSK812397 shows acceptable pharmacokinetic properties and bioavailability across species. GSK812397 has antiviral activity against a broad range of X4-utilizing strains of HIV-1 via a noncompetitive antagonism of the CXCR4 receptor.

3-Oxobetulin acetate is a derivative of the cholesterol biosynthesis inhibitor betulin. It inhibits the growth of P388 murine lymphocytic leukemia cells (EC50 = 0.12 µg ml), as well as human MCF-7 breast, SF-268 CNS, H460 lung, and KM20L2 colon cancer cells (GI50s = 8, 10.6, 5.2, and 12.7 µg ml, respectively), but not BxPC-3 pancreas or DU145 prostate cancer cells (GI50s = >10 µg ml for both). 3-Oxobetulin acetate inhibits replication of X4 tropic recombinant HIV (NL4.3-Ren) in MT-2 lymphoblastoid cells (IC50 = 13.4 µM). It is also active against L. donovani amastigotes when used at a concentration of 50 µM.

EPI-X4（hSA408–423 peptide），一种C-X-C 基序趋化因子受体 4（CXCR4）的拮抗剂，其 IC50 值为 8.6 μM。该化合物能够阻断 CXCL12 介导的信号传导，并有效抑制趋化因子引起的白血病细胞迁移与侵袭。此外，EPI-X4 在小鼠模型中展现了抗炎作用，并对 CXCR4 嗜性 HIV 具有抗病毒活性，同样的 IC50 为 8.6 μM。

KRH-1636 is an orally active, selective and extremely potent CXC chemokine receptor 4 antagonist. KRH-1636 exhibits a potent and selective anti-HIV-1 activity. KRH-1636 efficiently blocked replication of various T cell line-tropic (X4) HIV type 1 (HIV-1) in MT-4 cells and peripheral blood mononuclear cells through the inhibition of viral entry and membrane fusion via the CXC chemokine receptor (CXCR)4 coreceptor but not via CC chemokine receptor 5. KRH-1636 also inhibits binding of the CXC chemokine, stromal cell-derived factor 1alpha, to CXCR4 specifically and subsequent signal transduction. KRH-1636 prevented monoclonal antibodies from binding to CXCR4 without down-modulation of the coreceptor. KRH-1636 seems to be a promising agent for the treatment of HIV-1 infection.