MMV009085 is a potent and specific inhibitor of the Plasmodium falciparum hexose transporter PfHT1 and a potential antimalarial compound. MMV009085 is also a human glucose transporter inhibitor (antagonist) with strong inhibitory effects on glucose uptake (IC50= 2.6 μM) and parasite growth (EC50= 1.23±0.04 μM; 3D7).

Physicochemical Properties

Molecular Formula	C22H22N2O6
Molecular Weight	410.419886112213
Exact Mass	410.147
CAS #	298217-59-1
PubChem CID	3130863
Appearance	Off-white to pink solid powder
LogP	1.2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	8
Heavy Atom Count	30
Complexity	616
Defined Atom Stereocenter Count	0
InChi Key	XZBVMYTVRGGDKI-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H22N2O6/c25-11-3-1-9-23-19(27)13-5-7-15-18-16(8-6-14(17(13)18)20(23)28)22(30)24(21(15)29)10-2-4-12-26/h5-8,25-26H,1-4,9-12H2
Chemical Name	6,13-bis(4-hydroxybutyl)-6,13-diazatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),2,4(16),8,10-pentaene-5,7,12,14-tetrone
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

MMV009085 has an IC50 of 212±39 μM for blocking PfHT-1 transport activity and an EC50 of 1.23±0.04 μM and 0.720±0.05 μM for blocking the growth of Dd2 and 3D7, respectively. Furthermore, MMV009085's CC50 values on HepG2 and HEK293T cells are 1.92±0.85 μM and 2.46±0.03 μM, respectively[1]. In the assay on the uptake of glucose by free parasites, MMV009085 demonstrated an IC50 of 2.6 μM; its EC50 for preventing Plasmodium falciparum 3D7 growth in vitro was 0.987 μM, and it did so via blocking PfHT (EC50=0.795 μM) [1].

References

[1]. Structural Basis for Blocking Sugar Uptake into the Malaria Parasite Plasmodium falciparum.Cell. 2020 Oct 1;183(1):258-268.e12.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 100 mg/mL (~243.65 mM) H2O : < 0.1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 10 mg/mL (24.37 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 100.0 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4365 mL	12.1826 mL	24.3653 mL
	5 mM	0.4873 mL	2.4365 mL	4.8731 mL
	10 mM	0.2437 mL	1.2183 mL	2.4365 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.