TAK-779 是一种有效的，选择性的，非肽类 CCR5 和 CXCR3 拮抗剂，对 CCR5 的 Ki 值为 1.1 nM，同时可以有效地，选择性地抑制 R5 HIV-1，在 MAGI-CCR5 细胞中，EC50 和 EC90 值分别为 1.2 nM 和 5.7 nM。
CAS：229005-80-5
分子式：C33H39ClN2O2
分子量：531.13
纯度：98%
存储：Store at -20°C

Background:

TAK-779 is a potent and selective nonpeptide antagonist of CCR5 and CXCR3, with a Ki of 1.1 nM for CCR5, and effectively and selectively inhibits R5 HIV-1, with EC50 and EC90 of 1.2 nM and 5.7 nM, respectively, in MAGI-CCR5 cells. MIP-1α-CCR5|1 nM (IC50, in CHO/CCR5 cells)|MIP-1β-CCR5|1 nM (IC50, in CHO/CCR5 cells)|RANTES-CCR5|1.4 nM (IC50, in CHO/CCR5 cells)|MCP-1-CCR2b|27 nM (IC50, in CHO/CCR5 cells)|R5 HIV-1 (Ba-L)|1.2 nM (EC50, in MAGI-CCR5 cells)|R5 HIV-1 (KK)|1.6 nM (EC50, in PBMCs)|R5 HIV-1 (HHA)|3.2 nM (EC50, in PBMCs)|R5 HIV-1 (CTV)|3.5 nM (EC50, in PBMCs)|R5 HIV-1 (Ba-L)|3.7 nM (EC50, in PBMCs)|R5 HIV-1 (Ba-L)|5.7 nM (EC90, in MAGI-CCR5 cells)|R5 HIV-1 (HHA)|7.5 nM (EC90, in PBMCs)|R5 HIV-1 (Ba-L)|12.8 nM (EC90, in PBMCs)|R5 HIV-1 (KK)|20.8 nM (EC90, in PBMCs)|R5 HIV-1 (CTV)|27 nM (EC90, in PBMCs)|mCXCR3|369 nM (IC50, in PBMCs)

TAK-779 is a potent and selective nonpeptide antagonist of CCR5, with a Ki of 1.1 nM, and effectively and selectively inhibits R5 HIV-1, with EC50 and EC90 of 1.2 nM and 5.7 nM, respectively, in MAGI-CCR5 cells. TAK-779 less potently blocks the binding of [125I]-monocyte chemotactic protein 1 to CCR2b in CHO/CCR2b cells, with an IC50 for CCR2b of 27 nM. TAK-779 also completely inhibits the binding of [125I]-RANTES to CHO/CCR5 cells with an IC50 of 1.4 nM. TAK-779 (20 nM) selectively inhibits CCR5-mediated Ca2+-signaling. In addition, TAK-779 shows no inhibition on X4 HIV-1 strains[1]. TAK-779 is an antagonist of CXCR3, and inhibits the migration of T cells but not T cell proliferation[2].

TAK-779 (10 mg/kg per day, s.c.) significantly prolongs the allograft survival of the rat intestinal transplantation model. TAK-779 also decreases the number of CD4+ as well as CD8+ T cells in spleen, blood and recipient mesenteric lymph nodes (MLN)[2]. TAK-779 (150 µg per mouse, s.c.) supppresses the development of experimental autoimmune encephalomyelitis (EAE) in myelin oligodendrocyte glycoprotein (MOG)-immunized C57BL/6 mice. TAK-779 decreases the infiltration of CXCR3 and CCR5 bearing leukocytes into the spinal cord. TAK-779 does not alter myelin oligodendrocyte glycoprotein (MOG)-specific immune responses or affect the potential of MOG-specific T cells to transfer experimental autoimmune encephalomyelitis (EAE)[3].

[1]. Baba M, et al. A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5698-703. [2]. Takama Y, et al. Effects of a calcineurin inhibitor, FK506, and a CCR5/CXCR3 antagonist, TAK-779, in a rat small intestinal transplantation model. Transpl Immunol. 2011 Jul;25(1):49-55. [3]. Ni J, et al. The chemokine receptor antagonist, TAK-779, decreased experimental autoimmune encephalomyelitis by reducing inflammatory cell migration into the central nervous system, without affecting T cell function. Br J Pharmacol. 2009 Dec;158(8):2046-56. [4]. Gao P, et al. The unique target specificity of a nonpeptide chemokine receptor antagonist: selective blockade of two Th1 chemokine receptors CCR5 and CXCR3. J Leukoc Biol. 2003 Feb;73(2):273-80.