IPN60090 dihydrochloride (3 mg/kg for i.v.; 10 mg/kg for p.o.) has excellent pharmacokinetic properties, with CL=4.1 mL/min/kg, t1/2=1 hour, Cmax=19 μM, F%=89%[2].
IPN-60090 dihydrochloride (oral administration; 100 mg/kg; twice daily; 30 days) shows similar efficacy and target engagement to CB-839 (HY-12248) dosed orally at 250 mg/kg twice daily. And the 100 mg/kg BID dose of IPN-60090 is a tolerated dose for the following model study[2].IPN-60090 dihydrochloride (oral administration; 100 mg/kg; twice daily; 30 days; monotherapy or in combination with TAK228 (HY-13328)) causes tumor growth inhibition. IPN-60090 alone demonstrates robust in vivo target engagement in a dose-dependent manner. The glutamate/glutamine ratios and the free plasma concentrations of IPN-60090 at 4 hours post-dose on both day 4 and day 28 are all decreased[2]. Furthermore, IPN-60090 dihydrochloride in combination with TAK228 strongly causes an 85% tumor growth inhibition, IPN-60090 alone causes a 28% tumor growth inhibition in vivo[2].
| Animal Model: | Female CD-1 mice[2] |
| Dosage: | 3 mg/kg for i.v.; 10 mg/kg for p.o. (Pharmacokinetic Analysis) |
| Administration: | Intravenous injection and oral administration |
| Result: | CL (4.1 mL/min/kg), t1/2 (1 hour) for i.v.; Cmax (19 μM), F% (89%) for p.o.. |
| Animal Model: | Ru337 non-small cell lung cancer patient-derived xenograft (PDX) subcutaneous mouse model as monotherapy or in combination [2] |
| Dosage: | 100 mg/kg |
| Administration: | Oral administration; 100 mg/kg; twice daily; 30 days; monotherapy or in combination with TAK228 |
| Result: | Exhibited an improvement in the combination regimen group over either single agent. |
![2-Pyridineacetamide, 4-[(3,3-difluorocyclobutyl)oxy]-N-[6-[(3R)-3-fluoro-4-[4-[(methylamino)carbonyl]-1H-1,2,3-triazol-1-yl]butyl]-3-pyridazinyl]-6-methyl-, hydrochloride (1:2) Structure](/CAS/20211123/GIF/2102101-72-2.gif)