| Identification | Back Directory | [Name]
2-Propenamide-3,3-d2, N-[2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-[1-(methyl-d3)-1H-indol-3-yl]-2-pyrimidinyl]amino]phenyl]- | [CAS]
2403760-70-1 | [Synonyms]
Dosimertinib-d3
2-Propenamide-3,3-d2, N-[2-[[2-(dimethylamino)ethyl]methylamino]-4-methoxy-5-[[4-[1-(methyl-d3)-1H-indol-3-yl]-2-pyrimidinyl]amino]phenyl]- | [Molecular Formula]
C28H33N7O2 | [MOL File]
2403760-70-1.mol | [Molecular Weight]
499.62 |
| Hazard Information | Back Directory | [Uses]
Dosimertinib-d3-d3 is a potent and orally active EGFR inhibitor. Dosimertinib-d3-d3 decreases the expression of p-EGFR and p-ERK protein levels. Dosimertinib-d3-d3 shows antiproliferative and anti-tumor activity. Dosimertinib-d3-d3 has the potential for the research of non-small-cell lung cancer (NSCLC)[1]. | [in vivo]
Dosimertinib (0.75, 1.5, 3 mg/kg; oral gavage, daily for 24 days) shows anti-tumor activity in mouse[1].
Pharmacokinetic Parameters of Dosimertinib in Sprague-Dawley rats[1].
| detected compound | dosimertinib | | | | | administration route | i.v. | i.g. | i.g. | i.g. | | dose (mg/kg) | 2 | 2 | 6 | 12 | | C0 or Cmax (nM) | 277 ± 105 | 46.7 ± 10.7 | 113 ± 19.8 | 283 ± 137 | | Tmax (h) | | 4.17 ± 2.56 | 4.67 ± 1.63 | 5.00 ± 1.67 | | t1/2 (h) | 5.40 ± 1.84 | 3.76 ± 1.08 | 3.27 ± 0.43 | 4.04 ± 1.50 | | AUC0-t (nM·h) | 1070 ± 565 | 459 ± 191 | 1020 ± 313 | 2830 ± 1780 | | CL/F (L/h/kg) | 22.3 ± 11.1 | 32.2 ± 13.6 | 19.5 ± 5.1 | 14.9 ± 6.4 | | bioavailability (%) | | 41.2 | 29.6 | 43.0 |
Male Sprague-Dawley rats, 2 mg/kg iv; 2, 6, 12 mg/kg for i.g..
| Animal Model: | 18-20 g, BALB/c nude mice (H1975 mouse xenograft model)[1] | | Dosage: | 0.75, 1.5, 3 mg/kg | | Administration: | Oral gavage; daily for 24 days | | Result: | Significantly reduced tumor size with tumor growth inhibition (TGI) of 72.94% and 97.62% at 1.5, 3 mg/kg, respectively. |
| [References]
[1] Chen C, et al. Cyclization strategy leads to highly potent Bromodomain and extra-terminal (BET) Bromodomain inhibitors for the treatment of acute liver injury. Eur J Med Chem. 2022 Dec 16;247:115023. DOI:10.1016/j.ejmech.2022.115023 |
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