| Identification | Back Directory | [Name]
7H-Pyrrolo[2,3-d]pyrimidine-5-carboxamide, 4-amino-6-(2-cyclopropylethynyl)-7-[(3R,5S)-5-methyl-1-(1-oxo-2-propen-1-yl)-3-pyrrolidinyl]-N-[(1R)-1-phenylethyl]-, (2E)-2-butenedioate (1:1) | [CAS]
2758034-98-7 | [Synonyms]
7H-Pyrrolo[2,3-d]pyrimidine-5-carboxamide, 4-amino-6-(2-cyclopropylethynyl)-7-[(3R,5S)-5-methyl-1-(1-oxo-2-propen-1-yl)-3-pyrrolidinyl]-N-[(1R)-1-phenylethyl]-, (2E)-2-butenedioate (1:1) | [Molecular Formula]
C28H30N6O2.C4H4O4 | [MOL File]
2758034-98-7.mol | [Molecular Weight]
598.65 |
| Hazard Information | Back Directory | [Uses]
TAS2940 fumarate is a brain-penetrable, orally active, irreversible and selective pan-ERBB inhibitor. TAS2940 fumarate against wild-type HER2, HER2 V777L, and A775_G776insYVMA with IC50 values of 5.6 nM, 2.1 nM, and 1.0 nM, respectively. TAS2940 fumarate can be used for the study of tumors with HER2 and EGFR aberrations[1]. | [in vivo]
TAS2940 fumarate (3.1-25 mg/kg; po; once daily; for 14?days) inhibits tumor growth in xenograft mouse models with ERBB aberrations: HER2 amplification, HER2/EGFR exon 20 insertions, and EGFR vIII mutation[1].
PK parameters of TAS2940 after a single oral administration or multiple oral administrations for 7 days in male BALB/cAJcl-nu/nu mice[1].
1.19 | Administration | Dose (mg/kg) | Tmax (h) | Apparent T1/2 (h) | Cmax (ng/mL) | AUClast (ng?h/mL) | | Single administration | 6.25 | 0.33±0.14 | 2.15±2.15 | 601±111 | 795±229 | | Single administration | 12.5 | 0.25±0.00 | NC | 1590±220 | 2010±230 | | Single administration | 25 | 0.25±0.00 | 2.09 | 3580±190 | 5080±820 | | Repeated administrations for 7 days | 6.25 | 0.25±0.00 | 2.20±2.73 | 1170±300 | 972±239 | | Repeated administrations for 7 days | 12.5 | 0.33±0.14 | 0.69 | 2040±230 | 2800±460 | | Repeated administrations for 7 days | 25 | 0.42±0.14 | 0.76 | 3710±360 | 6180±310 |
| Animal Model: | 6-week-old male BALB/cAJcl-nu/nu mice injected with NCI-N87, MCF10A_HER2/insYVMA_v, or NCI-H1975 EGFR D770_N771insSVD cellsMCF10A_HER2/insYVMA_v[1] | | Dosage: | 3.1-25 mg/kg (0.5 w/v% HPMC) | | Administration: | po; once daily; for 14?days | | Result: | Inhibited tumor growth in xenograft mouse models. |
| [References]
[1] Kei Oguchi, et al. TAS2940, a novel brain-penetrable pan-ERBB inhibitor, for tumors with HER2 and EGFR aberrations. Cancer Sci. 2023 Feb;114(2):654-664. DOI:10.1111/cas.15617 |
|
|