| Identification | Back Directory | [Name]
DDD85646 | [CAS]
1215010-55-1 | [Synonyms]
DDD85646
DDD 85646
(DDD85646)
DDD85646 Hydrochloride
Benzenesulfonamide, 2,6-dichloro-4-[2-(1-piperazinyl)-4-pyridinyl]-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)-
African trypanosomiasis,N-myristoyltransferase,inhibit,DDD85646,Inhibitor,trypanosoma brucei,DNA/RNA Synthesis,NMT,Parasite | [Molecular Formula]
C21H24Cl2N6O2S | [MOL File]
1215010-55-1.mol | [Molecular Weight]
495.43 |
| Chemical Properties | Back Directory | [Melting point ]
>215°C (dec.) | [Boiling point ]
684.3±65.0 °C(Predicted) | [density ]
1.48±0.1 g/cm3(Predicted) | [storage temp. ]
Hygroscopic, -20°C Freezer, Under inert atmosphere | [solubility ]
DMSO (Slightly, Heated), Methanol (Slightly) | [form ]
Solid | [pka]
7.04±0.50(Predicted) | [color ]
Off-White to Yellow |
| Hazard Information | Back Directory | [Description]
DDD85646 is a moderately bioavailable pyrazole sulphonamide inhibitor of T. brucei N-myristoyltransferase (TbNMT) with an apparent Ki value of 1.44 nM. T. brucei is the parasite responsible for human African trypanosomiasis (HAT), also known as African sleeping sickness, and is transmitted through the tsetse fly. DDD85646 administration in mice (12.5 mg/kg for four days) ameliorated T. brucei in an acute mouse model of HAT. It less potently inhibits growth of T. cruzi (EC50 = 6.9 μM). | [Uses]
DDD85646 is a potent inhibitor of Trypanosoma brucei N-myristoyltransferase (TbNMT). | [in vivo]
DDD85646 (10, 50 mg/kg; Oral administration; 1) has moderate bioavailability (about 20%) in female NMRI mouse models, and the free drug level is higher than EC99 (EC99 is about 6 nM), which can effectively inhibit the proliferation of T. b. brucei[3].
DDD85646 (0-50 mg/kg; Oral administration; Twice a day; 4 days) kills Trypanosoma brucei by acting on TbNMT in T. b. brucei acute mouse model of HAT[3].
DDD85646 (50 mg/kg; Oral administration; Twice a day) shows significant antitrypanosomic activity in female NMRI mice models[3].
| Animal Model: | T. b. brucei acute mouse model of HAT[3] | | Dosage: | 0-50 mg/kg | | Administration: | Oral gavage (p.o.) | | Result: | Cured all animals in the T. b. brucei acute mouse model of HAT at a minimal oral dose of 12.5 mg/kg (b.i.d. for 4 days)
Prevented 99% of T. b. brucei proliferation
Parasite numbers dropped below detectable levels within 12 hours
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| [IC 50]
Trypanosoma | [storage]
Store at -20°C |
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