ACT-451840 is an orally bioactive, potent, low-toxic compound active against both susceptible and resistant Plasmodium falciparum strains. ACT-451840 has a rapid onset of action against all asexual blood stages of the parasite. ACT-451840's mode of action is similar to that of artemisinin analogues, with very rapid elimination of parasites. ACT-451840 may be utilized to study malaria.

Physicochemical Properties

Molecular Formula	C47H54N6O3
Molecular Weight	750.970071315765
Exact Mass	750.425
Elemental Analysis	C, 75.17; H, 7.25; N, 11.19; O, 6.39
CAS #	1984890-99-4
Related CAS #	1984890-99-4 (S-isomer);1839508-99-4 (racemic);
PubChem CID	53303762
Appearance	Off-white to light yellow solid powder
Density	1.2±0.1 g/cm3
Boiling Point	953.8±65.0 °C at 760 mmHg
Flash Point	530.6±34.3 °C
Vapour Pressure	0.0±0.3 mmHg at 25°C
Index of Refraction	1.652
LogP	6.74
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	12
Heavy Atom Count	56
Complexity	1340
Defined Atom Stereocenter Count	1
SMILES	O=C(C(CC1C=CC=CC=1)N(C(C=CC1C=CC(=CC=1)C(C)(C)C)=O)CC1C=CC(=CC=1)N1CCN(C(C)=O)CC1)N1CCN(CC2C=CC(C#N)=CC=2)CC1
InChi Key	BQZUYCCCNXOADJ-TVNMEPFQSA-N
InChi Code	InChI=1S/C47H54N6O3/c1-36(54)50-28-30-51(31-29-50)43-21-16-41(17-22-43)35-53(45(55)23-18-37-14-19-42(20-15-37)47(2,3)4)44(32-38-8-6-5-7-9-38)46(56)52-26-24-49(25-27-52)34-40-12-10-39(33-48)11-13-40/h5-23,44H,24-32,34-35H2,1-4H3/b23-18+/t44-/m0/s1
Chemical Name	(2E)-N-[[4-(4-Acetyl-1-piperazinyl)phenyl]methyl]-N-[(1S)-2-[4-[(4-cyanophenyl)methyl]-1-piperazinyl]-2-oxo-1-(phenylmethyl)ethyl]-3-[4-(1,1-dimethylethyl)phenyl]-2-propenamide
Synonyms	ACT-451840; ACT451840; ACT 451840
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	Ac-DEVD-CMK (100 μM; 24 h) prevents apoptosis produced by IDB [3]. Detroit 562 and FaDu human pharyngeal squamous cell carcinoma cell lines are resistant to citrate (10 mM)-induced p21 cleavage and G2/M accumulation when treated with Ac-DEVD-CMK (10 μM) for 36 hours [4].
ln Vivo	At 20 mg/kg, ACT-451840 (10 and 60 mg kg) begins to exhibit notable antimalarial effects (reduction of parasites). At 300 mg/kg, ACT-451840 demonstrates curative action, and at 100 mg/kg, it already has strong antimalarial effects. At 30 mg/kg, ACT-451840 exhibits a good decrease with 99.80% activity[2]. In a mouse model of Plasmodium berghei, ACT-451840 demonstrates effectiveness[2].
References	[1]. First-in-humans study of the safety, tolerability, and pharmacokinetics of ACT-451840, a new chemical entity with antimalarial activity. Antimicrob Agents Chemother. 2015;59(2):935-942. [2]. Discovery and Characterization of ACT-451840: an Antimalarial Drug with a Novel Mechanism of Action. ChemMedChem. 2016;11(18):1995-2014. [3]. Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling. PLoS Med. 2016;13(10):e1002138. Published 2016 Oct 4.
Additional Infomation	ACT-451840 has been used in trials studying Malaria.

Solubility Data

Solubility (In Vitro)

DMSO : 41.67 mg/mL (55.49 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (2.77 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 (2.77 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 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 (2.77 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	1.3316 mL	6.6581 mL	13.3161 mL
	5 mM	0.2663 mL	1.3316 mL	2.6632 mL
	10 mM	0.1332 mL	0.6658 mL	1.3316 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.