ACTIVE METABOLITES OF APILIMOD AND USES THEREOF
The present invention relates to compositions comprising one or more active metabolites of apilimod and methods for their use in treating cancer.
1 . A method for treating cancer in a human subject in need thereof, the method comprising administering an effective amount of a compound of Formula II to the subject:
wherein
R 1 is O or absent;
R 2 is H or OH; and
R 3 is H or OH.
2 . The method of claim 1 , wherein R 2 is OH.
3 . The method of claim 1 , wherein the effective amount of the compound is the amount effective to inhibit cellular PIKfyve activity in target cells in the subject.
4 . The method of claim 1 , wherein the cancer is a lymphoma, a melanoma, a renal cancer, or a colon cancer.
5 . The method of claim 4 , wherein the cancer is a lymphoma or melanoma.
6 . The method of claim 5 , wherein the cancer is refractory or resistant to standard therapy.
7 . The method of claim 5 , wherein the cancer is a non-Hodgkins lymphoma.
8 . The method of claim 4 , wherein the cancer is a renal cancer.
9 . The method of claim 8 , wherein the renal cancer is refractory or resistant to standard therapy.
10 . The method of claim 1 , wherein the compound is selected from the group consisting of STA-5864, STA-5944, STA-5908, STA-5919, STA-6035, and STA-6048.
11 . The method of claim 10 , wherein the compound is in the form a pharmaceutical composition.
12 . The method of claim 10 , wherein the compound comprises at least 95% or at least 99% enantiomeric excess of the (R)-enantiomer.
13 . The method of claim 10 , wherein the compound comprises at least 95% or at least 99% enantiomeric excess of the (S)-enantiomer.
14 . A pharmaceutical composition comprising a compound of Formula II wherein the compound comprises at least 95% or at least 99% enantiomeric excess of the (R)-enantiomer.
15 . A pharmaceutical composition comprising a compound of Formula II wherein the compound comprises at least 95% or at least 99% enantiomeric excess of the (S)-enantiomer.
16 . The pharmaceutical composition of claim 14 , wherein the compound is selected from the group consisting of STA-5864, STA-5944, STA-5908 STA-5919, STA-6035, and STA-6048.
17 . (canceled)
18 . A method for inhibiting cellular PIKfyve activity in a target cell, the method comprising contacting the target cell with an amount of a compound of Formula II effective to inhibit PIKfyve activity in the cell:
wherein
R 1 is O or absent;
R 2 is H or OH; and
R 3 is H or OH.
19 . The method of claim 18 , wherein R 2 is OH.
20 . The method of claim 18 , wherein the compound is selected from the group consisting of STA-5864, STA-5944, STA-5908, STA-5919, STA-6035, and STA-6048.
21 . (canceled)
22 . (canceled)
23 . (canceled)