Dosimertinib-d5 mesylate

• CAT Number: I042370
• CAS Number: 2403760-72-3
• Molecular Formula: C29H32D5N7O5S
• Molecular Weight: 600.74
• Purity: ≥95%
• Synonyms: 3,3-dideuterio-N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-[1-(trideuteriomethyl)indol-3-yl]pyrimidin-2-yl]amino]phenyl]prop-2-enamide;methanesulfonic acid
• InChI: InChI=1S/C28H33N7O2.CH4O3S/c1-7-27(36)30-22-16-23(26(37-6)17-25(22)34(4)15-14-33(2)3)32-28-29-13-12-21(31-28)20-18-35(5)24-11-9-8-10-19(20)24;1-5(2,3)4/h7-13,16-18H,1,14-15H2,2-6H3,(H,30,36)(H,29,31,32);1H3,(H,2,3,4)/i1D2,5D3
• InChIKey: FUKSNUHSJBTCFJ-FYWAFROVSA-N
• SMILES: CN1C=C(C2=CC=CC=C21)C3=NC(=NC=C3)NC4=C(C=C(C(=C4)NC(=O)C=C)N(C)CCN(C)C)OC.CS(=O)(=O)O

Dosimertinib-d5 (mesylate) is a potent and orally active EGFR inhibitor. Dosimertinib-d5 (mesylate) decreases the expression of p-EGFR and p-ERK protein levels. Dosimertinib-d5 (mesylate) shows antiproliferative and anti-tumor activity. Dosimertinib-d5 (mesylate) has the potential for the research of non-small-cell lung cancer (NSCLC)[1].
Dosimertinib mesylate (compound 2h) (1, 10, 100, 100 nM; 2h) decreases the expression of p-EGFR and p-ERK protein levels in a dose-dependent manner[1].
Dosimertinib mesylate (0.75, 1.5, 3 mg/kg; oral gavage, daily for 24 days) shows anti-tumor activity in mouse[1].
Pharmacokinetic Parameters of Dosimertinib mesylate 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

Sprague-Dawley rats, 2 mg/kg iv; 2, 6, 12 mg/kg for i.g..

Reference

[1]. Meng Y, et al. Discovery of Dosimertinib, a Highly Potent, Selective, and Orally Efficacious Deuterated EGFR Targeting Clinical Candidate for the Treatment of Non-Small-Cell Lung Cancer. J Med Chem. 2021 Jan 28;64(2):925-937.
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