YYA-021 is a novel and potent small-molecule CD4-mimic agent that acts as an HIV entry inhibitor by competitively inhibiting the interaction between an HIV-1 envelope glycoprotein gp120 and a cellular surface protein CD4. It has relatively high potency and low cytotoxicity. In TZM-bl cells infected with simian-human immunodeficiency virus isolate MNA (SHIV MNA) or HIV-1 MNA pseudotyped viruses, YYA-021 inhibited the entry of Envs of SHIV MNA and HIV-1. KD-247 (the anti-V3 loop mAb, 50 μg) caused 50% neutralization of HIV-1 MNA. However, in the presence of 20 μM of YYA-021, KD-247 (<0.05 μg) caused 50% neutralization of HIV-1 MNA, which suggested that the synergistic neutralization effect of YYA-021 and KD-247. In the presence of YYA-021, SHIV MNA became more sensitive to IgG. YYA-021 might have promise for intravenous administration when used combinatorially with anti-gp120 monoclonal antibodies.

Physicochemical Properties

Molecular Formula	C18H27N3O2
Molecular Weight	317.43
Exact Mass	317.21
CAS #	144217-65-2
Related CAS #	144217-65-2
PubChem CID	3107635
Appearance	White to off-white solid powder
LogP	3.151
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	2
Heavy Atom Count	23
Complexity	435
Defined Atom Stereocenter Count	0
SMILES	O=C(NC1=CC=C(C)C=C1)C(NC2CC(C)(C)NC(C)(C)C2)=O
InChi Key	AYAGJQPDCPRMNG-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H27N3O2/c1-12-6-8-13(9-7-12)19-15(22)16(23)20-14-10-17(2,3)21-18(4,5)11-14/h6-9,14,21H,10-11H2,1-5H3,(H,19,22)(H,20,23)
Chemical Name	N'-(4-methylphenyl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)oxamide
Synonyms	YYA-021; YYA 021; YYA021
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
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

ln Vitro	In vitro activity: YYA-021 enhances the neutralization sensitivity of simian-human immunodeficiency virus (SHIV) carrying the envelope from the clade B clinical human immunodeficiency virus type 1 (HIV-1) isolate MNA. Kinase Assay: YYA-021 is a small-molecule CD4 mimic that inhibits HIV entry, with high anti-HIV activity and low cytotoxicity. IC50 value: 8.4 μM Cell Assay: HIV IC50 (=8.4 μM) value of YYA-021 is determined by a single round assay using cYTA48P virus and TZM-bl cells. YYA-021 is broadly distributed in tissues, probably as a result of its hydrophobicity. The plasma concentrations of YYA-021 in both species remained at micromolar levels for several hours post-injection.
ln Vivo	Rats and rhesus macaques
Animal Protocol	14 mg/kg (rats), 13.4 mg/kg (rhesus macaques); i.v. injection Rat, dog and monkey
References	J Gen Virol.2013 Dec;94(Pt 12):2710-6;Bioorg Med Chem.2013 Dec 15;21(24):7884-9.

Solubility Data

Solubility (In Vitro)

DMSO:<1 mg/mL Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.88 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 (7.88 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (7.88 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	3.1503 mL	15.7515 mL	31.5030 mL
	5 mM	0.6301 mL	3.1503 mL	6.3006 mL
	10 mM	0.3150 mL	1.5752 mL	3.1503 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.