Aplaviroc

InvivoChem Cat #:V3644CAS #:461443-59-4Purity >=98%

Description: Aplaviroc (formerly known as AK-602; GW-873140; GW873140A; ONO-4128; GSK 873140), a SDP (spirodiketopiperazine) derivative, is a CCR5 entry inhibitor with IC50s of 0.1-0.4 nM for HIV-1Ba-L, HIV-1JRFL and HIV-1MOKW and with the potential treatment of HIV infection. Aplaviroc binds specifically to human cellular CC chemokine receptor 5 (CCR5) and demonstrates potent anti-human immunodeficiency virus activity in vitro in the subnanomolar range. In vitro studies show that aplaviroc selectively inhibits the binding of a particular monoclonal antibody, 45531, to CCR5. Aplaviroc specifically blocked the binding of macrophage inflammatory protein 1alpha (MIP-1alpha) to CCR5 with a high affinity (K(d) of approximately 3 nM), potently blocked human immunodeficiency virus type 1 (HIV-1) gp120/CCR5 binding and exerted potent activity against a wide spectrum of laboratory and primary R5 HIV-1 isolates, including multidrug-resistant HIV-1 (HIV-1(MDR)) (50% inhibitory concentration values of 0.1 to 0.6 nM) in vitro. AK602 competitively blocked the binding to CCR5 expressed on Chinese hamster ovary cells of two monoclonal antibodies, 45523, directed against multidomain epitopes of CCR5, and 45531, specific against the C-terminal half of the second extracellular loop (ECL2B) of CCR5. AK602, despite its much greater anti-HIV-1 activity than other previously published CCR5 inhibitors, including TAK-779 and SCH-C, preserved RANTES (regulated on activation normal T-cell expressed and secreted) and MIP-1beta binding to CCR5(+) cells and their functions, including CC-chemokine-induced chemotaxis and CCR5 internalization, while TAK-779 and SCH-C fully blocked the CC-chemokine/CCR5 interactions. Pharmacokinetic studies revealed favorable oral bioavailability in rodents. These data warrant further development of AK602 as a potential therapeutic for HIV-1 infection.

References: J Virol. 2004 Aug; 78(16):8654-62.

Related CAS#: 461023-63-2 (HCl salt)

-20C for 3 years in powder form

Synonym: GSK-873140; GSK 873140; GSK873140; AK 602; AK-602; AK602; AK 602; GW873140A; GW-873140; GW873140; GW 873140; ONO-4128; ONO 4128; ONO4128; Aplaviroc hydrochloride
Chemical Name: Benzoic acid, 4-(4-(((3R)-1-butyl-3-((R)-cyclohexylhydroxymethyl)-2, 5-dioxo-1, 4, 9-triazaspiro(55)undec-9-yl)methyl)phenoxy)-
InChi Key: GWNOTCOIYUNTQP-FQLXRVMXSA-N
InChi Code: InChI=1S/C33H43N3O6/c1-2-3-19-36-30(38)28(29(37)24-7-5-4-6-8-24)34-32(41)33(36)17-20-35(21-18-33)22-23-9-13-26(14-10-23)42-27-15-11-25(12-16-27)31(39)40/h9-16, 24, 28-29, 37H, 2-8, 17-22H2, 1H3, (H, 34, 41)(H, 39, 40)/t28-, 29-/m1/s1
SMILES Code: O=C(O)C1=CC=C(OC2=CC=C(CN(CC3)CCC3(N(CCCC)C([CH]([CH](C4CCCCC4)O)N5)=O)C5=O)C=C2)C=C1