DSM705 is a pyrrole-based inhibitor of dihydroorotate dehydrogenase (DHODH). DSM705 displays nanomolar potency against Plasmodium DHODH and Plasmodium parasites and has no inhibitory effect on mammalian DHODH. DSM705 is a potent antimalarial compound.

Physicochemical Properties

Molecular Formula	C19H19F3N6O
Molecular Weight	404.388973474503
Exact Mass	404.157
CAS #	2653225-38-6
Related CAS #	DSM705 hydrochloride
PubChem CID	155908677
Appearance	Typically exists as solid at room temperature
LogP	3.1
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	29
Complexity	613
Defined Atom Stereocenter Count	1
SMILES	CC1=C(NC=C1C2(CC2)C3=CN=C(C=C3)C(F)(F)F)C(=O)N[C@H](C)C4=NC=NN4
InChi Key	JUBPRXDFKLPILK-LLVKDONJSA-N
InChi Code	InChI=1S/C19H19F3N6O/c1-10-13(8-24-15(10)17(29)27-11(2)16-25-9-26-28-16)18(5-6-18)12-3-4-14(23-7-12)19(20,21)22/h3-4,7-9,11,24H,5-6H2,1-2H3,(H,27,29)(H,25,26,28)/t11-/m1/s1
Chemical Name	3-methyl-N-[(1R)-1-(1H-1,2,4-triazol-5-yl)ethyl]-4-[1-[6-(trifluoromethyl)pyridin-3-yl]cyclopropyl]-1H-pyrrole-2-carboxamide
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	IC50: 95 nM (P. falciparum DHODH), 52 nM (P. vivax DHODH)[1]
ln Vitro	DSM705 exhibits inhibitory activity with no inhibition of the human enzyme against P. falciparum DHODH (PfDHODH, IC50=95 nM), P. vivax DHODH (PvDHODH, IC50=52 nM), and Pf3D7 cells (EC50=12 nM).
ln Vivo	At a dose of 50 mg/kg, DSM705 (3-200 mg/kg; po twice a day for 6 days) offers the highest rate of parasite death and completely reduces parasitemia by days 7-8[1]. Swiss outbred mice showing high oral bioavailability (74%, 70%), apparent t1/2 (3.4, 4.5 h), and Cmax (2.6, 20 μM) for DSM705 (2.6 and 24 mg/kg; a single po)[1]. Mice treated with DSM705 (2.3 mg/kg; single intravenous) show plasma clearance (CL=2.8 mL/min/kg) and Vss (1.3 L/kg)[1].
Animal Protocol	Animal/Disease Models: SCID (severe combined immunodeficient) mouse were inoculated with parasites[1] Doses: 3, 10, 20, 50, 100, 200 mg/kg Route of Administration: Po twice a day for 6 days Experimental Results: Killed parasites in a dose dependent manner and fully suppressed parasitemia by days 7-8. Animal/Disease Models: Swiss Outbred Mice[1] Doses: 2.6 and 24 mg/kg for po; 2.3 mg/kg for iv (pharmacokinetic/PK Analysis) Route of Administration: A single po and iv Experimental Results: Po: F= 74/70%, t1/2=3.4/4.5 h, Cmax=2.6/20 μM. Iv: CL=2.8 mL/min/kg, Vss=1.3 L/kg.
References	[1]. Palmer MJ, et, al. Potent Antimalarials with Development Potential Identified by Structure-Guided Computational Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series. J Med Chem. 2021 May 13;64(9):6085-6136.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4729 mL	12.3643 mL	24.7286 mL
	5 mM	0.4946 mL	2.4729 mL	4.9457 mL
	10 mM	0.2473 mL	1.2364 mL	2.4729 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.