CCR5 Antagonist

Maraviroc (UK-427857) is a selective CCR5 antagonist with activity against human HIV.

TAK-779 is a potent and selective nonpeptide antagonist of CCR5 and CXCR3, with a K_i 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.

Cenicriviroc (TAK-652) is an orally active, dual CCR2/CCR5 antagonist, also inhibits both HIV-1 and HIV-2, and displays potent anti-inflammatory and antiinfective activity.

BMS-813160 is a potent and selective CCR2/5 dual antagonist. BMS-813160 binds with CCR2 and CCR5 with IC₅₀s of 6.2 and 3.6 nM, respectively. BMS-813160 can be used for the research of inflammation.

Cenicriviroc Mesylate (TAK-652 Mesylate) is a dual CCR2/CCR5 antagonist, also inhibits both HIV-1 and HIV-2, and displays potent anti-inflammatory and antiinfective activity.

Met-RANTES (human) acetate is the acetate form of Met-RANTES (human) (HY-P4191). Met-RANTES (human) acetate is the antagonist for CCR1 and CCR5. Met-RANTES (human) acetate inhibits chemokines human MIP-1α and MIP-1β with IC₅₀ of 5 and 2 nM. Met-RANTES (human) acetate reduces bone destruction and ameliorates rats adjuvant-induced arthritis (AIA).

TAK-220 is a selective and orally bioavailable CCR5 antagonist, with IC₅₀s of 3.5 nM and 1.4 nM for inhibition on the binding of RANTES and MIP-1α to CCR5, respectively, but shows no effect on the binding to CCR1, CCR2b, CCR3, CCR4, or CCR7; TAK-220 also selectively inhibits HIV-1, with EC₅₀s of 1.2 nM (HIV-1 KK), 0.72 nM (HIV-1 CTV), 1.7 nM (HIV-1 HKW), 1.7 nM (HIV-1 HNK), 0.93 nM (HIV-1 HTN), and 0.55 nM (HIV-1 HHA), and EC₉₀s of 12 nM (HIV-1 KK), 5 nM (HIV-1 CTV), 12 nM (HIV-1 HKW), 28 nM (HIV-1 HNK), 15 nM (HIV-1 HTN), and 4 nM (HIV-1 HHA) in PBMCs.

Vicriviroc maleate (SCH-417690 maleate; SCH-D maleate) is a potent, selective, oral bioavailable and CNS penetrated antagonist of CCR5, with a K_i of 2.5 nM, and also inhibits HIV-1 in PBMC cells, with IC₉₀s of 3.3 nM (JrFL), 2.8 nM (ADA-M), 1.8 nM (301657), 4.9 nM (JV1083) and 10 nM (RU 570).

Aplaviroc (AK 602) hydrochloride, a SDP derivative, is a CCR5 antagonist, with IC₅₀s of 0.1-0.4 nM for HIV-1_Ba-L, HIV-1_JRFL and HIV-1_MOKW.

PF-0463481 succinate is a potent and orally active dual CCR2/CCR5 antagonist with comparable human and rodent CCR2 potency (rat IC₅₀=20.8 nM), and displays 10-20 fold less rodent CCR5 potency (rat IC₅₀=470 nM). PF-0463481 succinate is safe and well-tolerated and has the potential for the study of diabetic nephropathy.

PF-0463481 is a potent and orally active dual CCR2/CCR5 antagonist with comparable human and rodent CCR2 potency (rat IC₅₀=20.8 nM), and displays 10-20 fold less rodent CCR5 potency (rat IC₅₀=470 nM). PF-0463481 is safe and well-tolerated and has the potential for the study of diabetic nephropathy.

AZD-5672 is an orally active, potent, and selective CCR5 antagonist (IC₅₀=0.32 nM). AZD-5672 shows moderate activity against the hERG ion channel (binding IC₅₀=7.3 μM). AZD5672 is a substrate of human P-gp, and inhibits P-gp-mediated digoxin transport (IC₅₀=32 μM). AZD-5672 can be used for the research of rheumatoid arthritis.

Met-RANTES (human) is the antagonist for CCR1 and CCR5. Met-RANTES (human) inhibits chemokines human MIP-1α and MIP-1β with IC₅₀ of 5 and 2 nM. Met-RANTES (human) reduces bone destruction and ameliorates rats adjuvant-induced arthritis (AIA).

Aplaviroc (AK 602), a SDP derivative, is a CCR5 antagonist, with IC₅₀s of 0.1-0.4 nM for HIV-1_Ba-L, HIV-1_JRFL and HIV-1_MOKW.

Ancriviroc (SCH-351125) is an orally active CCR5 antagonist with an IC₅₀ value of 13 nM against hCCR5. Ancriviroc specifically binds to hCCR5, blocks ligand-induced signal transduction, calcium influx, GTPγS binding, chemotaxis, ligand binding, and HIV-1 entry, induces conformational changes in CCR5, and inhibits infection and replication of R5-tropic HIV-1.

INCB9471 is a potent, selective and orally active CCR5 antagonist. INCB9471 shows anti-HIV-1 activity.

LUF8100 is a dual-target antagonist of CCR2/CCR5 with pK_i values for CCR2 and CCR5 of 5.23 and 4.97 respectively. LUF8100 can be used for research on immune homeostasis and cancer.

CCR5 antagonist 2 (Compound 25) is a CCR5 antagonist with an IC₅₀ of 8.34 nM. CCR5 antagonist 2 shows broad-spectrum anti-HIV-1 activities.

BMS-741672 is a selective and orally active CCR2 antagonist with an IC₅₀ of 1.1 nM. BMS-741672 shows >700-fold selective for CCR2 than CCR5.

CCR5 antagonist 1 is a CCR5 antagonist which can inhibit HIV replication extracted from WO 2004054974 A2.