PD-404182 (PD 404182; PD404182) is a novel and potent inhibitor of KDO 8-P synthase with antiangiogenic and antiviral activity (anti-HIV and anti-herpes simplex virus). It inhibits KDO 8-P synthase with a Ki of 26 nM. It is effective against gram negative bacteria.

Physicochemical Properties

Molecular Formula	C11H11N3S
Molecular Weight	217.29
Exact Mass	217.067
CAS #	72596-74-8
PubChem CID	6603967
Appearance	Light yellow to yellow solid powder
LogP	1.022
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	0
Heavy Atom Count	15
Complexity	313
Defined Atom Stereocenter Count	0
SMILES	C1=CC=C2C(=C1)C3=NCCCN3C(=N)S2
InChi Key	JNENSSREQFBZGT-UHFFFAOYSA-N
InChi Code	InChI=1S/C11H11N3S/c12-11-14-7-3-6-13-10(14)8-4-1-2-5-9(8)15-11/h1-2,4-5,12H,3,6-7H2
Chemical Name	3,4-dihydro-2H,6H-benzo[e]pyrimido[1,2-c][1,3]thiazin-6-imine
Synonyms	PD404182 PD 404182 PD-404182
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	Asymmetric dimethylarginine (ADMA) in EC is increased by around 70% in response to PD 404182 (20 μM) [1]. In vitro, PD 404182 (50-100 μM; 18 hours) reduces endothelial tube formation without compromising the integrity of cell membranes or causing cytotoxicity [1]. With an IC50 of 1 μM, PD 404182 suppresses HIV-1 in seminal plasma[2]. When applied to various human cell lines, freshly activated PBMCs, primary CD4+ T lymphocytes, macrophages, dendritic cells, and lactobacilli in the normal vaginal flora, PD 404182 (300 μM; 30 min) shows minimal toxicity [2].
Cell Assay	Cell viability assay [1] Cell Types: Human dermal microvascular endothelial cells (EC) Tested Concentrations: 10-300 μM Incubation Duration: 24 hrs (hours) Experimental Results: No cytotoxicity is induced.
References	[1]. Ghebremariam YT, et, al. A novel and potent inhibitor of dimethylarginine dimethylaminohydrolase: a modulator of cardiovascular nitric oxide. J Pharmacol Exp Ther. 2014 Jan; 348(1): 69-76. [2]. Chamoun-Emanuelli AM, et, al. Evaluation of PD 404,182 as an anti-HIV and anti-herpes simplex virus microbicide. Antimicrob Agents Chemother. 2014; 58(2): 687-97.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~230.11 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (11.51 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 (11.51 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 (11.51 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	4.6021 mL	23.0107 mL	46.0214 mL
	5 mM	0.9204 mL	4.6021 mL	9.2043 mL
	10 mM	0.4602 mL	2.3011 mL	4.6021 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.