COMPOSITIONS AND METHODS FOR MAKING AND USING SMALL MOLECULES FOR TUBULIN-TARGETED THERAPY IN THE TREATMENT OF CANCERS AND RELATED CONDITIONS
Compounds, compositions and methods disclosed herein are effective for treating a subject having or suspected of developing a health condition, for example, cancer (i.e., brain cancer or a cancer metastasizing to the brain). The method of treating cancer can include administering a pharmaceutical composition to a subject, the composition including at least one of the novel compounds disclosed herein, and optionally, one or more additional anti-cancer therapies. The compounds, compositions and methods can be further used for drug screening and other methods of detection and isolation.
1 . A salt of RGN6024 formed with a pharmaceutically acceptable acid.
2 . The salt of claim 1 , wherein the acid is selected from the group consisting of benzene sulfonic acid, ethane-1,2-disulfonic acid, ethane sulfonic acid, hydrochloric acid, methane sulfonic acid, naphthalene-1,5-disulfonic acid, naphthalene sulfonic acid, and sulfuric acid.
3 . The salt of claim 2 , wherein the RGN6024:acid stoichiometry of benzene sulfonic acid, methane sulfonic acid, naphthalene-1,5-disulfonic is 1:1.
4 . The salt of claim 2 , wherein the RGN6024:acid stoichiometry of ethane sulfonic acid, naphthalene sulfonic acid is 1:2.
5 . The salt of claim 2 , wherein the RGN6024:acid stoichiometry of ethane-1,2-disulfonic acid is 2:3.
6 . The salt of claim 1 , wherein the melting point is about 150° C. to 160° C.
7 . A salt of RGN6024, selected from the group consisting of RGN6024 besylate, RGN6024 edisylate, RGN6024 esylate, RGN6024 hydrochloride, RGN6024 mesylate, RGN6024 napadisylate, RGN6024 napsylate, and RGN6024 sulfate.
8 . The salt of claim 7 , wherein RGN6024 besylate, RGN6024 mesylate, and RGN6024 napadisylate comprises a 1:1 RGN6024:acid stoichiometry.
9 . The salt of claim 7 , wherein the RGN6024 esylate and RGN6024 napsylate comprises a 1:2 RGN6024:acid stoichiometry.
10 . The salt of claim 7 , wherein the RGN6024 edisylate comprises a 2:3 RGN6024:acid stoichiometry.
11 . A spray dried dispersion composition comprising RGN6024 and a polymer.
12 . The composition of claim 11 , wherein the polymer is selected from a group consisting of: hydroxypropyl methylcellulose acetate succinate (HPMCAS) MG, polyvinylpyrrolidone vinyl acetate (PVP/VA) 64, polyvinylpyrrolidone (PVP) 12 PF, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, and hydroxypropyl-beta-cyclodextrin (HP-β-CD).
13 . The composition of claim 11 , wherein the drug:polymer weight ratio is about 20:80 w/w.
14 . The composition of claim 11 , wherein the polymer is hydroxypropyl-beta-cyclodextrin (HP-β-CD), having a drug:polymer weight ratio of about 20:80 w/w RGN6024: HP-β-CD.
15 . The composition of claim 11 , wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS) MG.
16 . The composition of claim 15 , further comprising poloxamer 407 (polyoxyethylene, polyoxypropylene block polymer), wherein the RGN6024:HPMCAS MG:poloxamer 407 weight ratio is about 20:60:20 w/w/w.
17 . A lipid-based composition comprising RGN6024 and one or more lipid-solubilizing excipients; wherein the one or more lipid solubilizing excipients are selected from lauroyl polyoxyl/macrogol 32 glycerides, caprylocaproyl polyoxyl-8 glycerides and polyethylene glycol.
18 . The composition of claim 17 , wherein the composition comprises RGN6024, lauroyl polyoxyl/macrogol 32 glycerides, and caprylocaproyl polyoxyl-8 glycerides.
19 . The composition of claim 17 , wherein the composition comprises RGN6024, lauroyl polyoxyl/macrogol 32 glycerides, and polyethylene glycol.
20 . The composition of claim 17 , wherein the composition comprises RGN6024, lauroyl polyoxyl/macrogol 32 glycerides, caprylocaproyl polyoxyl-8 glycerides, and polyethylene glycol.