Compositions for ameliorating cell proliferative disorders and methods of making and using them
In alternative embodiments, the invention provides apratoxin F and apratoxin G compounds, which include apratoxin F and apratoxin G stereoisomers, derivatives and analogs compositions and methods. In alternative embodiments, the invention provides pharmaceutical compositions and formulations comprising apratoxin F (compound 6 of FIG. 1 ) and apratoxin G (compound 7 of FIG. 1 ) and their stereoisomers, derivatives and analogs. In alternative embodiments, pharmaceutical compositions and formulations of the invention are administered in an amount sufficient to treat, prevent and/or ameliorate a disease or condition that can be ameliorated by decreasing or inhibiting cell growth, e.g., pathological, uncontrolled or unwanted cell growth, e.g., a cancer or a metastases, or any disease or condition (e.g., allergy) or infection having a hyperproliferative cell growth component.
1. A composition comprising an isolated compound consisting essentially of:
compound having the formula
wherein
R 1 =H, CH 3
R 2 =H, CH 3 , i-Pr, t-Bu
R 3 =H, CH 3 , i-Pr, CH(CH 3 )CH 2 CH 3 , CH 2 CH(CH 3 ) 2
R 4 =H, CH 3 , i-Pr, CH(CH 3 )CH 2 CH 3 , CH 2 CH(CH 3 ) 2
R 5 =H, CH 3 , i-Pr, CH(CH 3 )CH 2 CH 3 , CH 2 CH(CH 3 ) 2
R 6 =CH 2 PhOH, CH 2 PhOMe, CH 2 Ph
X=O, S, N.
2. The composition of claim 1 , formulated as a pharmaceutical composition, or formulated for enteral or parenteral administration.
3. A formulation or a pharmaceutical composition comprising:
a composition of claim 1 .
4. A method for decreasing or inhibiting cell growth comprising administering to a cell or contacting a cell with a composition of claim 1 .
5. A method for treating and/or ameliorating:
(i) a disease or condition that can be responsive to or ameliorated by decreasing or inhibiting cell growth,
(ii) a pathological, uncontrolled or unwanted cell growth,
(iii) a cancer or a metastases, or
(iv) any disease or condition or infection having a hyperproliferative cell growth component,
comprising:
(a) administering a composition of claim 1 , in an amount sufficient to treat and/or ameliorate a disease or a condition:
(i) that can be treated or ameliorated by decreasing or inhibiting cell growth,
(ii) a pathological, uncontrolled or unwanted cell growth,
(iii) a cancer or a metastases, or
(iv) any disease or condition or infection having a hyperproliferative cell growth component; or
(b) the method of (a), wherein the administration is to a human or a mammal.
6. A method for ameliorating an inflammatory disease or a condition that can be ameliorated by decreasing or inhibiting cell growth or proliferation, comprising:
(a) administering a composition of claim 1 , in an amount sufficient to treat or ameliorate a disease or a condition:
(i) that can be ameliorated by decreasing or inhibiting cell growth,
(ii) a pathological, uncontrolled or unwanted cell growth,
(iii) a cancer or a metastases, or
(iv) a disease or a condition or an infection having a hyperproliferative cell growth component;
(b) the method of (a), wherein the administration is to a human or a mammal.
7. A kit comprising a composition of claim 1 .
8. The formulation or pharmaceutical composition of claim 3 , wherein the
compound is selected from the group consisting of: an apratoxin F (compound 6 of FIG. 1 ); an apratoxin G (compound 7 of FIG. 1 ); thereof; or
(b) the formulation or pharmaceutical composition of (a), wherein the compound is formulated for administration in vivo; or for enteral or parenteral administration, or as a tablet, pill, geltab, liquid, lotion, aerosol or implant.
9. A method for decreasing or inhibiting cell growth comprising:
(a) administering to a cell or contacting a cell with a compound of claim 8 ; or
(b) the method of (a), wherein the administration is in vitro, ex vivo or in vivo.
10. The formulation or a pharmaceutical composition of claim 3 , wherein the compound comprises an apratoxin F (compound 6 of FIG. 1 ).
11. The formulation or a pharmaceutical composition of claim 3 , wherein the compound comprises an apratoxin G (compound 7 of FIG. 1 ).
12. The composition of claim 1 , wherein the compound is apratoxin F (compound 6 of FIG. 1 ).
13. The composition of claim 1 , wherein the compound is apratoxin G (compound 7 of FIG. 1 ).
14. The method of claim 4 , wherein the administration is in vitro.
15. The method of claim 4 , wherein the administration is ex vivo.
16. The method of claim 4 , wherein the administration is in vivo.
17. The formulation or a pharmaceutical composition of claim 1 , wherein the compound is formulated for administration in vivo.
18. The formulation or a pharmaceutical composition of claim 17 , wherein the compound is formulated for enteral or parenteral administration, or as a tablet, pill, geltab, liquid, lotion, aerosol or implant.