JAK1 pathway inhibitors for the treatment of cytokine-related disorders
This disclosure relates to JAK1 pathway inhibitors and the use thereof in treating cytokine-related diseases or disorders such as cytokine release syndrome (CRS), hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndrome (MAS), and CAR-T-cell-related encephalopathy syndrome (CRES).
1. A method for treating cytokine release syndrome in a subject, said method comprising administering to the subject a JAK1 selective pathway inhibitor which is {1-{1-[3-fluoro-2 -(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the JAK1 selective pathway inhibitor is {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile adipic acid salt.
3. The method of claim 1 , further comprising administering tocilizumab to said subject.
4. The method of claim 1 , further comprising administering a corticosteroid to said subject.
5. The method of claim 1 , further comprising administering prednisone to said subject.
6. The method of claim 1 , further comprising administering tocilizumab and a corticosteroid to said subject.
7. The method of claim 3 , wherein the JAK1 selective pathway inhibitor is {1-{1-[3-fluoro-2-(trifluoromethyl)sonicotinoyl]piperidin-4-yl}-3[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile adipic acid salt.
8. The method of claim 4 , wherein the JAK1 selective pathway inhibitor is {1-{1-[3 -fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3 [4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile adipic acid salt.
9. The method of claim 5 , wherein the JAK1 selective pathway inhibitor is {1-{1-[3 -fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3[4-(7H-pyrrolo[2,3-d]pyrimidin-4-y1)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile adipic acid salt.
10. The method of claim 6 , wherein the JAK1 selective pathway inhibitor is {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3 [4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile adipic acid salt.
11. The method of claim 1 , wherein the treating comprises ameliorating or inhibiting cytokine release syndrome in the subject.
12. A method for treating cytokine release syndrome in a subject, said method comprising administering to the subject a monotherapy which is {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3 [4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, or a pharmaceutically acceptable salt thereof.
13. The method of claim 12 , wherein the treating comprises ameliorating or inhibiting cytokine release syndrome in the subject.
14. A method for treating cytokine release syndrome in a subject, said method comprising administering to the subject a monotherapy which is {1-{1[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile adipic acid salt.
15. The method of claim 14 , wherein the treating comprises ameliorating or inhibiting cytokine release syndrome in the subject.