| Description |
Pirmitegravir is a potent and first-in-class inhibitor of allosteric integrase (ALLINI) that targets LEDGF/p75 binding site. Pirmitegravir displays picomolar IC50 in human PBMCs with a >24,000 therapeutic index against HIV-1. Pirmitegravir harbors outstanding anti-virus and safety properties[1].
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| Related Catalog |
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| Target |
allosteric integrase (ALLINI)[1]
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| In Vitro |
Pirmitegravir (Compound STP0404) inhibits dual tropic HIV-189.6 at 1.4 nM IC50 in CEMx174 cells[1]. Pirmitegravir (Compound STP0404) is a highly potent ALLINI with picomolar to single-digit nanomolar IC50 values that inhibits both wild type and Ral-resistant HIV-1 strains[1]. Pirmitegravir (Compound STP0404) displays IC50 of 0.41 nM against HIV-1NL4-3 without observable cytotoxicity in human PBMCs at 10 μM (TC50 >10μM)[1].
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| In Vivo |
Pirmitegravir (Compound STP0404) displays appropriate PK profiles for once daily administration[1]. Pirmitegravir (Compound STP0404) lacks micronucleus-inducing and bone marrow cell proliferation inhibitory potentials in rats (500, 1000 and 2000 mg/kg/day), supporting that STP0404 is not genotoxic[1]. Assessment of Pharmacokinetics (PK) profile of Pirmitegravir (Compound STP0404) in rat and dog[1]. PK Values Rat Dog 10 mg/kg (p.o) 5 mg/kg (i.v) 2 mg/kg (p.o) 2 mg/kg (i.v) T1/2 (hr) 4.56 3.83 6.90 6.11 AUC (hr.nM) 78074 42676 4683 9260 Cmax (nM) 21380 - 3983 - Ft (%) 92.8 - 50.6 - Animal Model: SD rats and beagle dogs[1] Dosage: 1, 2, 5, and 10 mg/kg Administration: i.v.; p.o. Result: The half-life (T1/2) was 3–7 h, and oral bioavailability (Ft) was 50–93% in these two animal species. Systemic exposure, which was determined by area under the curve and maximum concentration of STP0404 in plasma (AUC and Cmax), increased dose-dependently from 2 to 10 mg/kg.
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| References |
[1]. Maehigashi T, et al. A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site. PLoS Pathog. 2021;17(7):e1009671.
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