| Identification | Back Directory | [Name]
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) | [CAS]
2102101-72-2 | [Synonyms]
IPN60090 (dihydrochloride)
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) | [Molecular Formula]
C24H28ClF3N8O3 | [MOL File]
2102101-72-2.mol | [Molecular Weight]
568.99 |
| Hazard Information | Back Directory | [Description]
IACS-6274, also known as IPN60090, is a potent, selective and orally active glutaminase inhibitor with potential antineoplastic and immunostimulating activities. IPN60090 selectively targets, binds to and inhibits human glutaminase, an enzyme that is essential for the conversion of the amino acid glutamine into glutamate. | [Uses]
IPN-60090 dihydrochloride is an orally active and highly selective inhibitor of glutaminase 1 (GLS1; IC50=31 nM), with no activity observed against GLS-2. IPN-60090 dihydrochloride exhibits excellent physicochemical and pharmacokinetic properties in vivo. IPN-60090 dihydrochloride can be used for solid tumors research, such as lung and ovarian cancers[1][2]. | [in vivo]
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. |
| [References]
[1] Maria Emilia Di Francesco, et al. Gls1 inhibitors for treating disease. WO2016004404A2.
[2] Michael J Soth, et al. Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties. J Med Chem. 2020 Nov 12;63(21):12957-12977. DOI:10.1021/acs.jmedchem.0c01398 |
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