AN3661, a potent antimalarial lead compound, targets the cleavage and polyadenylate specificity factor homolog subunit 3 (PfCPSF3) of Plasmodium falciparum. AN3661 inhibits infection by laboratory-adapted strains of Plasmodium falciparum (meIC50=32 nM), Ugandan field isolates (meIC50=64 nM) and mice with P. berghei and P. falciparum.

Physicochemical Properties

Molecular Formula	C10H11BO4
Molecular Weight	206.002943277359
Exact Mass	206.075
CAS #	1268335-33-6
PubChem CID	50898347
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	15
Complexity	246
Defined Atom Stereocenter Count	0
InChi Key	CEVOKIPNIZQANN-UHFFFAOYSA-N
InChi Code	InChI=1S/C10H11BO4/c12-9(13)5-4-7-2-1-3-8-6-15-11(14)10(7)8/h1-3,14H,4-6H2,(H,12,13)
Chemical Name	3-(1-hydroxy-3H-2,1-benzoxaborol-7-yl)propanoic acid
Synonyms	AN 3661; AN-3661
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 tests using fresh Ugandan field isolates (mean ex vivo IC50=64 nM) reveal that AN3661 is active at nanomolar (IC50=20-56 nM) concentrations against laboratory strains of P. falciparum known to be susceptible (3D7) or resistant (W2, Dd2, K1, HB3, FCR3, and TM90C2B). With a CC50 of 60.5 μM against Jurkat cells, AN3661 demonstrated low cytotoxicity against mammalian cell lines. All other CC50 values were greater than the maximum dose tested, which was 25 μM or above [1]. Transcripts of Plasmodium falciparum are not as stable when AN3661 is present [1].
ln Vivo	In mice with a 4-day ED90 of 0.34 mg/kg, AN3661 (50-200 mg.kg; oral; once daily for 4 days) suppresses Plasmodium berghei infection[1]. Starting on the third day of infection, AN3661 was given orally for four days. Four days after therapy commenced, the ED90 was 0.57 mg/kg[1].
Animal Protocol	Animal/Disease Models: Plasmodium berghei infected mice (malaria model) [1] Doses: 50, 100, 200 mg/kg Route of Administration: Oral; one time/day for 4 days Experimental Results: Parasitaemia was quickly controlled, ED90 is 0.34 mg/kg. Daily doses of 50 mg/kg and 100 mg/kg prolonged survival of mice, and mice treated with 200 mg/kg daily demonstrated long-term healing effects.
References	[1]. Sonoiki E, et al. A potent antimalarial benzoxaborole targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue. Nat Commun. 2017;8:14574. Published 2017 Mar 6.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~1213.59 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (10.10 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 20.8 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: ≥ 2.08 mg/mL (10.10 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 20.8 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: ≥ 2.08 mg/mL (10.10 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 20.8 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	4.8544 mL	24.2718 mL	48.5437 mL
	5 mM	0.9709 mL	4.8544 mL	9.7087 mL
	10 mM	0.4854 mL	2.4272 mL	4.8544 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.