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NBD-14189 

Cat. No. M29399
NBD-14189  Structure
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Biological Activity

NBD-14189 is a potent HIV-1 entry antagonist with an IC50 of 89 nM against the HIV-1HXB2 pseudovirus. NBD-14189 binds to HIV-1 gp120 and shows potent antiviral activity (EC50<200 nM).

Chemical Information
Molecular Weight 428.4
Formula C18H16F4N4O2S
CAS Number 2234273-72-2
Form Solid
Solubility (25°C) DMSO 100 mg/mL (ultrasonic)
Storage 4°C, protect from light, dry, sealed
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] Cheryl A Stoddart, et al. Viruses. Comparative Pharmacokinetics of a Dual Inhibitor of HIV-1, NBD-14189, in Rats and Dogs with a Proof-of-Concept Evaluation of Antiviral Potency in SCID-hu Mouse Model

[2] Natalie Losada, et al. J Med Chem. HIV-1 gp120 Antagonists Also Inhibit HIV-1 Reverse Transcriptase by Bridging the NNRTI and NRTI Sites

[3] Francesca Curreli, et al. J Med Chem. Preclinical Optimization of gp120 Entry Antagonists as anti-HIV-1 Agents with Improved Cytotoxicity and ADME Properties through Rational Design, Synthesis, and Antiviral Evaluation

[4] Francesca Curreli, et al. Eur J Med Chem. Structure-based lead optimization to improve antiviral potency and ADMET properties of phenyl-1H-pyrrole-carboxamide entry inhibitors targeted to HIV-1 gp120

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