DSM705hydrochloride
PRODUCTS SPECIFICATIONS
DESCRIPTION
Overview
| MDL | - |
|---|---|
| Molecular Weight | 440.85 |
| Molecular Formula | C19H20ClF3N6O |
| SMILES | C[C@H](C1=NC=NN1)NC(C2=C(C(C3(C4=CC=C(N=C4)C(F)(F)F)CC3)=CN2)C)=O.[H]Cl |
Summary
DSM705 hydrochloride, an orally active antimalarial compound, is a pyrrole-based Dihydroorotate Dehydrogenase (DHODH) inhibitor. DSM705 hydrochloride exhibits nanomolar potency against Plasmodium DHODH and Plasmodium parasites ( IC 50 =95, 52 nM for P. falciparum and P. vivax DHODH, respectively), with no inhibition of mammalian DHODHs [1] .
IC50 & Target
IC50: 95 nM ( P. falciparum DHODH), 52 nM ( P. vivax DHODH) [1]
In Vitro
DSM705 hydrochloride shows inhibitory activity against P. falciparum DHODH ( Pf DHODH, IC 50 =95 nM), P. vivax DHODH ( Pv DHODH, IC 50 =52 nM) and Pf 3D7 cells (EC 50 =12 nM), with no inhibition of the human enzyme [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
DSM705 (3-200 mg/kg; p.o. twice a day for 6 days) hydrochloride provides the maximum rate of parasite killing at the dose of 50 mg/kg and fully suppresses parasitemia by days 7-8
[1]
.
DSM705 (2.6 and 24 mg/kg; a single p.o.) hydrochloride exhibits high oral bioavailability (74%, 70%), apparent t
1/2
(3.4, 4.5 h) and C
max
(2.6, 20 μM) in Swiss outbred mice
[1]
.
DSM705 (2.3 mg/kg; a single i.v.) hydrochloride exhibits plasma clearance (CL=2.8 mL/min/kg) and V
ss
(1.3 L/kg) in mice
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | SCID mice were inoculated with parasites [1] |
| Dosage: | 3, 10, 20, 50, 100, 200 mg/kg |
| Administration: | P.o. twice a day for 6 days |
| Result: | Killed parasite in a dose dependent manner and fully suppressed parasitemia by days 7-8. |
| Animal Model: | Swiss Outbred Mice [1] |
| Dosage: | 2.6 and 24 mg/kg for p.o.; 2.3 mg/kg for i.v. (Pharmacokinetic Analysis) |
| Administration: | A single p.o. and i.v. |
| Result: |
P.o.: F=74/70%, t
1/2
=3.4/4.5 h, C
max
=2.6/20 μM.
I.v.: CL=2.8 mL/min/kg, V ss =1.3 L/kg. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
Methanol : 250 mg/mL ( 567.09 mM ; Need ultrasonic)
DMSO : 100 mg/mL ( 226.83 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.2683 mL | 11.3417 mL | 22.6835 mL |
| 5 mM | 0.4537 mL | 2.2683 mL | 4.5367 mL |
| 10 mM | 0.2268 mL | 1.1342 mL | 2.2683 mL |
