| Identification | Back Directory | [Name]
1H-Pyrrolo[2,3-b]pyridine-5-acetic acid, 4-(4-chlorophenyl)-α-(1,1-dimethylethoxy)-2,3,6-trimethyl-1-[(1-methyl-1H-pyrazol-4-yl)methyl]-, (αS)- | [CAS]
2245231-10-9 | [Synonyms]
Pirmitegravir
1H-Pyrrolo[2,3-b]pyridine-5-acetic acid, 4-(4-chlorophenyl)-α-(1,1-dimethylethoxy)-2,3,6-trimethyl-1-[(1-methyl-1H-pyrazol-4-yl)methyl]-, (αS)- | [Molecular Formula]
C27H31ClN4O3 | [MOL File]
2245231-10-9.mol | [Molecular Weight]
495.02 |
| Chemical Properties | Back Directory | [Boiling point ]
706.1±60.0 °C(Predicted) | [density ]
1.25±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
1.52±0.30(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
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]. | [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. |
| [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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