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DDD85646 

Cat. No. M27958
DDD85646  Structure
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Biological Activity

DDD85646 is a potent inhibitor of trypanosoma brucei N-myristoyltransferase (TbNMT IC50=2 nm; hNMTIC50=4 nm). The enzyme N-myristoyltransferase (NMT) is a potential agent target for human African trypanosomiasis.

Chemical Information
Molecular Weight 495.43
Formula C21H24Cl2N6O2S
CAS Number 1215010-55-1
Form Solid
Solubility (25°C) DMSO 100 mg/mL (ultrasonic)
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Wouter W Kallemeijn, et al. Cell Chem Biol. Validation and Invalidation of Chemical Probes for the Human N-myristoyltransferases

[2] Irena Corbic Ramljak, et al. PLoS Pathog. Cellular N-myristoyltransferases play a crucial picornavirus genus-specific role in viral assembly, virion maturation, and infectivity

[3] David A Robinson, et al. Acta Crystallogr F Struct Biol Commun. Identification and structure solution of fragment hits against kinetoplastid N-myristoyltransferase

[4] Daniel Paape, et al. PLoS Negl Trop Dis. Using a non-image-based medium-throughput assay for screening compounds targeting N-myristoylation in intracellular Leishmania amastigotes

[5] Adam J Roberts, et al. Biochem J. Biochemical and genetic characterization of Trypanosoma cruzi N-myristoyltransferase

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