Ganaplacide (KAF156) HCl is the first orally bioactive imidazopiperazine antimalarial. Ganaplacide HCl has activity against a variety of malaria parasites such as drug-resistant parasites. Ganaplacide HCl has insecticidal activity against asexual and sexual blood stages as well as hepatic stages.

Physicochemical Properties

Molecular Formula	C22H24CLF2N5O
Molecular Weight	447.908670425415
Exact Mass	447.163
CAS #	2751586-94-2
Related CAS #	Ganaplacide;1261113-96-5
PubChem CID	154925625
Appearance	White to yellow solid powder
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	31
Complexity	604
Defined Atom Stereocenter Count	0
SMILES	Cl.FC1C=CC(=CC=1)C1=C(NC2C=CC(=CC=2)F)N2CCN(C(CN)=O)C(C)(C)C2=N1
InChi Key	XCXQBXGWYRFISY-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H23F2N5O.ClH/c1-22(2)21-27-19(14-3-5-15(23)6-4-14)20(26-17-9-7-16(24)8-10-17)28(21)11-12-29(22)18(30)13-25;/h3-10,26H,11-13,25H2,1-2H3;1H
Chemical Name	2-amino-1-[3-(4-fluoroanilino)-2-(4-fluorophenyl)-8,8-dimethyl-5,6-dihydroimidazo[1,2-a]pyrazin-7-yl]ethanone;hydrochloride
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	Plasmodium
ln Vitro	Ganaplacide hydrochloride (KAF156) hydrochloride demonstrates blood schizonticide efficacy against drug-susceptible and drug-resistant strains of P. falciparum at 50% inhibitory concentrations of 6 to 17.4 nM [1].
ln Vivo	In order to stop the spread of the parasite to Anopheles mosquitoes, KAF156 has cidal action against mature Plasmodium falciparum gametocytes [1]. In a malaria mouse model used as a preventive measure, ganaplacide hydrochloride (KAF156) hydrochloride (1–15 mg/kg; oral) provides complete protection [1].
Animal Protocol	Animal/Disease Models: Mice (causal prophylactic rodent malaria model)[1] Doses: 1-15 mg/kg Route of Administration: po Experimental Results: A single oral dose of 10 mg of KAF156/kg administered 2 h before infection was fully protective.
References	[1]. Kuhen KL, et al. KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission. Antimicrob Agents Chemother. 2014;58(9):5060-5067. [2]. Leong FJ, et al. A first-in-human randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study of novel Imidazolopiperazine KAF156 to assess its safety, tolerability, and pharmacokinetics in healthy adult volunteers. Antimicrob Agents Chemother. 2014;58(11):6437-6443.

Solubility Data

Solubility (In Vitro)

DMSO : 100 mg/mL (223.26 mM) H2O : 33.33 mg/mL (74.41 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.58 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 (5.58 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 (5.58 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	2.2326 mL	11.1630 mL	22.3259 mL
	5 mM	0.4465 mL	2.2326 mL	4.4652 mL
	10 mM	0.2233 mL	1.1163 mL	2.2326 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.