Vicriviroc maleate (formerly known as SCH 417690; SCH-D), the maleate salt of vicriviroc, is a novel, potent, selective, orally bioavailable and CNS penetrant antagonist of CCR5 entry inhibitor of HIV-1 with a Ki 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). Vicriviroc can be administered once daily. Vicriviroc is recommended for once-daily use. Vicriviroc attaches itself to the CCR5 receptor's extracellular surface in a tiny hydrophobic pocket that lies between the transmembrane helices. When the virus binds to this pocket, the extracellular segment of CCR5 undergoes a conformational change that stops gp120 from binding to the target cell, thereby blocking the virus's entry into the target cell entirely.

Physicochemical Properties

Molecular Formula	C32H42F3N5O6
Molecular Weight	649.70098
Exact Mass	649.308
Elemental Analysis	C, 59.16; H, 6.52; F, 8.77; N, 10.78; O, 14.77
CAS #	599179-03-0
Related CAS #	306296-47-9; 541503-81-5 (malate); 599179-03-0; 541503-48-4 (HCl)
PubChem CID	6451165
Appearance	White to beige solid powder
Boiling Point	608.1ºC at 760mmHg
LogP	4.026
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	13
Rotatable Bond Count	8
Heavy Atom Count	46
Complexity	892
Defined Atom Stereocenter Count	2
SMILES	CC1(N2C[C@H](C)N([C@H](C3=CC=C(C(F)(F)F)C=C3)COC)CC2)CCN(C(C4=C(C)N=CN=C4C)=O)CC1.O=C(O)/C=C\C(O)=O
InChi Key	GXINKQQWHLIBJA-UCIBKFKQSA-N
InChi Code	InChI=1S/C28H38F3N5O2.C4H4O4/c1-19-16-35(14-15-36(19)24(17-38-5)22-6-8-23(9-7-22)28(29,30)31)27(4)10-12-34(13-11-27)26(37)25-20(2)32-18-33-21(25)3;5-3(6)1-2-4(7)8/h6-9,18-19,24H,10-17H2,1-5H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t19-,24-;/m0./s1
Chemical Name	(Z)-but-2-enedioic acid;(4,6-dimethylpyrimidin-5-yl)-[4-[(3S)-4-[(1R)-2-methoxy-1-[4-(trifluoromethyl)phenyl]ethyl]-3-methylpiperazin-1-yl]-4-methylpiperidin-1-yl]methanone
Synonyms	SCH417690; SCH 417690; SCH-417690; SCH-D
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	CCR5; HIV-1; CCR5 ( Ki = 2.5 nM ); HIV-1 (301657) ( IC90 = 1.8 nM ); HIV-1 (ADA-M) ( IC90 = 2.8 nM ); HIV-1 (JrFL) ( IC90 = 3.3 nM ); HIV-1 (JV1083) ( IC90 = 4.9 nM ); HIV-1 (RU 570) ( IC90 = 10 nM )
ln Vitro	Vicriviroc maleate (SCH-417690 maleate; SCH-D maleate) inhibits HIV-1 in PBMC cells with IC90s of 3.3 (JrFL), 2.8 (ADA-M), 1.8 (301657), 4.9 (JV1083), and 10 nM (RU 570). It is a strong, selective, and oral bioavailable inhibitor of CCR5. Furthermore, Vicriviroc maleate exhibits weak activity against hERG activity (IC50, 5.8 μM) and has mean IC50 and IC90 values of 0.45 nM and 4 nM for a panel of HIV isolates[1]. Vicriviroc maleate suppresses RANTES-induced signaling with a mean IC50 of 4.2 ± 1.3 nM and inhibits the chemotactic response to MIP-1α with IC50 values below 1 nM. Vicriviroc maleate, with geometric mean EC50s of 0.04-2.3 nM and IC90s of 0.45-18 nM, potently suppresses all the tested viral isolates[2].
ln Vivo	Vicriviroc maleate (SCH-417690 maleate; SCH-D maleate; 10 mg/kg) does not cause acute CNS or GI side effects in rats and exhibits good oral availability in both monkeys and rats[1].
Cell Assay	For three to seven days, ficoll-purified peripheral blood mononuclear cells (PBMCs) are stimulated in vitro with 50 U/mL of interleukin-2 (IL-2) and 5 μg/mL of phytohemagglutinin (PHA). Following a 1-hour incubation period at 37°C with an equal volume of culture medium containing compound (Vicriviroc), the cells are resuspended at 4 × 106/mL in complete medium (RPMI, 10% fetal bovine serum [FBS], 50 U/mL IL-2), seeded into 96-well plates (2 × 105/well), and infected in triplicate using 25 to 100 50% tissue culture infectious doses (TCID50) per well of viral inoculum for three to four hours. After two rounds of washing in phosphate-buffered saline (PBS) to get rid of any remaining virus, the cells are cultured in the compound for four to six days. The extracellular p24 antigen in the supernatants is measured using an enzyme-linked immunosorbent assay to determine the amount of HIV-1 replication. With Graphpad PRISM software, the 50% effective concentrations (EC50s) and EC90s for each virus are calculated[2].
References	[1]. Piperazine-based CCR5 antagonists as HIV-1 inhibitors. IV. Discovery of 1-[(4,6-dimethyl-5-pyrimidinyl)carbonyl]- 4-[4-[2-methoxy-1(R)-4-(trifluoromethyl)phenyl]ethyl-3(S)-methyl-1-piperazinyl]- 4-methylpiperidine (Sch-417690/Sch-D), a potent, highly selective, and orally bioavailable CCR5 antagonist. J Med Chem. 2004 May 6;47(10):2405-8. [2]. Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2005 Dec;49(12):4911-9.
Additional Infomation	Vicriviroc Maleate is a maleate salt form of Vicriviroc, a piperazine-based CCR5 receptor antagonist with activity against human immunodeficiency virus. Vicriviroc is designed to bind to CCR5 and inhibit the entry of HIV into CD4 cells. Drug Indication Treatment of human immunodeficiency virus (HIV-1) infection

Solubility Data

Solubility (In Vitro)

DMSO: 50~100 mg/mL (77~149.8 mM) Water: ~100 mg/mL Ethanol: ~100 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.85 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.85 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (3.85 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.5392 mL	7.6959 mL	15.3917 mL
	5 mM	0.3078 mL	1.5392 mL	3.0783 mL
	10 mM	0.1539 mL	0.7696 mL	1.5392 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.