TAK-220

Research use only, not for human use.

A potent, specific, orally bioavailable CCR5 antagonist that blocks the binding of MIP-1α to CCR5 with IC50 of 1.4 nM.

A potent, specific, orally bioavailable CCR5 antagonist that blocks the binding of MIP-1α to CCR5 with IC50 of 1.4 nM; shows no affinity for CCR1, CCR2b, CCR3, CCR4, or CCR7; inhibits the replication of 6 CCR5-using (R5) HIV-1 clinical isolates in peripheral blood mononuclear cells (PBMCs) with mean EC90 of 13 nM; selectively inhibits R5 HIV-1 replication by interfering with coreceptor-mediated entry of the virus into host cells; exhibits a good pharmacokinetic profile in monkeys.HIV Infection Phase 1 Clinical.

TAK-220 is a selective CCR5 antagonist, with IC50s of 3.5 nM and 1.4 nM for inhibition on the binding of RANTES and MIP-1α to CCR5 in CHO cells, respectively, but shows no effect on the binding to CCR1, CCR2b, CCR3, CCR4, or CCR7. TAK-220 (0-1000 nM) interacts with CCR5 but not with RANTES and inhibits the CCR5-mediated Casup>2+ signaling. TAK-220 inhibits R5 HIV-1 (JR-FL) envelope-mediated membrane fusion, with an IC50 value of 0.42 nM, but does not alter X4 HIV-1 (HXB2) envelope-mediated membrane fusion. 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. TAK-220 shows potent inhibitory activity against the R5 isolates, with IC50s of 3.12 nM against HIV-1 R5-08, 13.47 nM against HIV-1 R5-06, and 2.26 nM against HIV-1 R5-18. TAK-220 (>100 nM) has no toxicity in uninfected PBMCs.

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TAK 220 | TAK220

GPCR/G Protein

Chemokine Receptor

Chemokine Receptor

Infection

HIV Infection

333994-00-6

553.1353

C31H41ClN4O3

>98% (HPLC)

10 mM in DMSO

O=C(C1CCN(C(C)=O)CC1)N(CCCN2CCC(CC3=CC=C(C(N)=O)C=C3)CC2)C4=CC=C(C)C(Cl)=C4

4-Piperidinecarboxamide, 1-acetyl-N-[3-[4-[[4-(aminocarbonyl)phenyl]methyl]-1-piperidinyl]propyl]-N-(3-chloro-4-methylphenyl)-

(-20℃)

With Ice Pack

≥ 2 years