FNDR-20123 free base is an effective, safe and first-in-class anti-malarial HDAC inhibitor (antagonist) with IC50 of 31 nM and 3 nM against Plasmodium and human HDAC respectively. FNDR-20123 free base has anti-malarial activity against the asexual phase (IC50=41 nM) and hemorrhagic phase (male gametocytes IC50=190 nM) of Plasmodium falciparum. FNDR-20123 free base inhibits HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8 with IC50s of 25, 29, 2, 11, and 282 nM respectively, and inhibits class III HDAC subtypes at nanomolar concentrations.

Physicochemical Properties

Molecular Formula	C21H23N5O2
Molecular Weight	377.44
Exact Mass	377.185
CAS #	1267502-34-0
Related CAS #	FNDR-20123;2641930-61-0
PubChem CID	50991199
Appearance	Typically exists as solid at room temperature
LogP	2.1
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	6
Heavy Atom Count	28
Complexity	497
Defined Atom Stereocenter Count	0
InChi Key	MTAWGBVDXCFYOF-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H23N5O2/c27-21(23-28)19-9-5-17(6-10-19)14-26-15-20(22-24-26)18-7-3-16(4-8-18)13-25-11-1-2-12-25/h3-10,15,28H,1-2,11-14H2,(H,23,27)
Chemical Name	N-hydroxy-4-[[4-[4-(pyrrolidin-1-ylmethyl)phenyl]triazol-1-yl]methyl]benzamide
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

Targets	human HDAC 3 nM (IC50) Plasmodium HDAC 31 nM (IC50) HDAC1 25 nM (IC50) HDAC2 29 nM (IC50) HDAC3 2 nM (IC50) HDAC6 11 nM (IC50) HDAC8 282 nM (IC50) Plasmodium
ln Vitro	FNDR-20123 is effective against every resistant strain that has been studied thus far, which will be very helpful in getting rid of the rapidly spreading parasite that is resistant to drugs[1].
ln Vivo	In addition, FNDR-20123 (10–50 mg/kg; po; bw for 4 days) can considerably lower parasitaemia in a mouse model of P. falciparum infection[1].
Animal Protocol	Animal/Disease Models: P. falciparum Pf3D70087/N9 in NODscidIL2Rγnull mice (engrafted with human erythrocytes)[1] Doses: 10 and 50 mg/kg Route of Administration: Po; bw for 4 days Experimental Results: Resulted in a significant reduction in parasitaemia with 6.5% and 2.57% parasitaemia at 10 and 50 mg/kg, respectively.
References	[1]. Discovery of FNDR-20123, a histone deacetylase inhibitor for the treatment of Plasmodium falciparum malaria. Malar J. 2020;19(1):365. Published 2020 Oct 12.

Solubility Data

Solubility (In Vitro)

DMSO : 35.71 mg/mL (94.61 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.08 mg/mL (5.51 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. 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 (5.51 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 (5.51 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 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	2.6494 mL	13.2471 mL	26.4943 mL
	5 mM	0.5299 mL	2.6494 mL	5.2989 mL
	10 mM	0.2649 mL	1.3247 mL	2.6494 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.