Heteroaryl compounds for kinase inhibition
Compounds and pharmaceutical compositions that modulate kinase activity, including mutant EGFR and mutant HER2 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including mutant EGFR and mutant HER2 activity, are described herein.
1. A method for treating non-small cell lung cancer (NSCLC) with one or more insertion mutations in the exon 20 domain of the epidermal growth factor receptor (EGFR) comprising administering to a subject in need thereof, a therapeutically effective amount of Compound (I) having the following structure:
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the subject is an adult human subject.
3. The method of claim 2 , wherein the therapeutically effective amount of Compound (I) or a pharmaceutically acceptable salt thereof is about 0.1 mg to about 500 mg per day.
4. The method of claim 3 , wherein the therapeutically effective amount of Compound (I) or a pharmaceutically acceptable salt thereof is administered orally.
5. The method of claim 3 , wherein the therapeutically effective amount of Compound (I) or a pharmaceutically acceptable salt thereof is administered once, twice, three times, four times, five times, or six times per day.
6. The method of claim 5 , wherein the therapeutically effective amount of Compound (I) or a pharmaceutically acceptable salt thereof is administered once per day.
7. The method of claim 6 , wherein the therapeutically effective amount of Compound (I) or a pharmaceutically acceptable salt thereof is administered orally.
8. The method of claim 7 , wherein the therapeutically effective amount of Compound (I) or a pharmaceutically acceptable salt thereof is administered in one or more capsules.
9. The method of claim 8 , wherein each capsule comprises greater than about 80% w/w of Compound (I) or a pharmaceutically acceptable salt thereof.
10. The method of claim 9 , wherein each capsule comprises greater than about 90% of Compound (I) or a pharmaceutically acceptable salt thereof.
11. The method of claim 8 , wherein each capsule comprises less than about 0.05 g, and more than about 0.04 g of Compound (I) or a pharmaceutically acceptable salt thereof.
12. A method for inhibiting EGER with one or more insertion mutations in the exon 20 domain in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of Compound (I) having the following structure:
or a pharmaceutically acceptable form thereof.
13. The method of claim 12 , wherein the subject is an adult human subject.
14. The method of claim 13 , wherein the therapeutically effective amount of Compound (I) or a pharmaceutically acceptable salt thereof is about 0.1 mg to about 500 mg per day.
15. The method of claim 14 , wherein the therapeutically effective amount of Compound (I) or a pharmaceutically acceptable salt thereof is administered orally.
16. The method of claim 14 , wherein the therapeutically effective amount of Compound (I) or a pharmaceutically acceptable salt thereof is administered once, twice, three times, four times, five times, or six times per day.
17. The method of claim 16 , wherein the therapeutically effective amount of Compound (I) or a pharmaceutically acceptable salt thereof is administered once per day.
18. The method of claim 17 , wherein the therapeutically effective amount of Compound (I) or a pharmaceutically acceptable salt thereof is administered orally.
19. The method of claim 18 , wherein the therapeutically effective amount of Compound (I) or a pharmaceutically acceptable salt thereof is administered in one or more capsules.
20. The method of claim 19 , wherein each capsule comprises greater than about 80% w/w of Compound (I) or a pharmaceutically acceptable salt thereof.
21. The method of claim 20 , wherein each capsule comprises greater than about 90% w/w of Compound (I) or a pharmaceutically acceptable salt thereof.
22. The method of claim 21 , wherein each capsule comprises less than about 0.05 g, and more than about 0.04 g of Compound (I) or a pharmaceutically acceptable salt thereof.