SSH-2 (slingshot-2) inhibitors and methods for making and using them

A pharmaceutical compound, a formulation or a composition selected from the group consisting of:

• wherein R1 and R2 can be any alkoxy group, methoxy- group, ethoxy- group, butoxy- group, or a group having a longer alkyl or alkene group;
• or any combination thereof, and R3 can be any alkyl group, including a methyl, ethyl, propyl or butyl or longer alkyl or alkene group, or any combination thereof;
• wherein R1 can be any alkoxy group, including methoxy, ethoxy, butoxy, etc.) or having a longer alkyl or alkene group, or any combination thereof;
• wherein R1 and R2 can be any alkoxy group, including methoxy, ethoxy, butoxy, etc.) or having a longer alkyl or alkene group, or any combination thereof;
• 3-[(4,5dimethoxy-3-oxo-1,3-dihydro-2-benzofuran-1-yl)amino]-4-methylbenzoic acid;
• 2-ethoxy-5-(4-phenylpiperidine-1-sulfonyl)benzoic acid;
• 3-[bis(2-methoxyethyl)sulfamoyl]benzoic acid;
• wherein R1 can be any alkyl group, including a methyl, ethyl, propyl or butyl or longer alkyl or alkene group, or any combination thereof;
• wherein Me is a methyl group and COO− is a carboxy group;
• wherein R1 and R2 can be any alkyl group, including a methyl, ethyl, propyl or butyl or longer alkyl or alkene group, or any combination thereof;
• wherein Me is a methyl group and COO− is a carboxy group;
• wherein COO− is a carboxy group;
• wherein R1, R2, R3, R4, and R5 can be any alkyl group, including a methyl, ethyl, propyl or butyl or longer alkyl or alkene group, or any combination thereof;
• wherein Me is a methyl group and Et is an ethyl group;
• wherein R1 can be any alkyl group, including a methyl, ethyl, propyl or butyl or longer alkyl or alkene group, or any combination thereof
• 3-[2-(2,6-dichlorophenoxy)ethyl]-4-oxophthalazine-1-carboxylate;
• ZINC03429974,
• wherein Me is a methyl group and COO− is a carboxy group;
• any combination thereof, and
• any analog or derivative, or stereoisomer or bioisostere thereof.

A method for inhibiting or slowing the dephosphorylating of a cofilin in a cell, comprising:

• (i) (a) providing a pharmaceutical, formulation or composition
• comprising a compound ZINC04307500 having the structure:
• or any analog or derivative thereof or a stereoisomer or a bioisostere thereof;
• and
• (b) contacting the pharmaceutical compound, formulation or composition of (a) with a SSH-2 or SlingShot-2 polypeptide in the cell in an amount sufficient to inhibit or slow the dephosphorylating of the cofilin;
• or
• (ii) the method of (i), wherein the contacting of the compound or composition with the SSH-2 or SlingShot-2 polypeptide is in vitro, ex vivo or in vivo.

A method for inhibiting or preventing the binding of a cofilin to an F-actin, comprising:

• (i) providing a pharmaceutical, formulation or composition
• comprising a compound ZINC04307500 having the structure:
• or any analog or derivative thereof or a stereoisomer or a bioisostere thereof;
• and
• (b) contacting the pharmaceutical compound, formulation or composition of (a) with a SSH-2 or SlingShot-2 polypeptide in the cell in an amount sufficient to inhibit or slow the dephosphorylating of the cofilin, thereby inhibiting or preventing the binding of a cofilin to an F-actin;
• or
• (ii) the method of (i), wherein the contacting of the compound or composition with the SSH-2 is in vitro, ex vivo or in vivo.

A method for inhibiting or preventing the binding of a cofilin to an F-actin, comprising:

• (i) (a) providing a pharmaceutical, formulation or composition
• comprising a compound ZINC04307500 having the structure:
• and
• (b) contacting the pharmaceutical compound, formulation or composition of (a) with a SSH-2 or SlingShot-2 polypeptide in the cell in an amount sufficient to inhibit or slow the dephosphorylating of the cofilin, thereby inhibiting or preventing the binding of a cofilin to an F-actin;
• or
• (ii) the method of (i), wherein the contacting of the compound or composition with the SSH-2 is in vitro, ex vivo or in vivo.

A method for stabilizing F-actin polymers, actin filaments, or actin-comprising microtubules, in a cell, comprising:

• (i) (a) providing a pharmaceutical, formulation or composition
• comprising a compound ZINC04307500 having the structure:
• or any analog or derivative thereof stereoisomer or bioisostere thereof;
• and
• (b) administering the pharmaceutical compound, formulation or composition of (a) to the cell or, inserting the pharmaceutical compound or composition into the cell, in an amount sufficient to stabilize the F-actin polymer, actin filament, or actin-comprising microtubule;
• or
• (ii) the method of (i), wherein the administering of the pharmaceutical compound, formulation or composition to the cell is in vitro, ex vivo or in vivo.

A method for stabilizing F-actin polymers, actin filaments, or actin-comprising microtubules, in a cell, comprising:

• (i) (a) providing a pharmaceutical, formulation or composition
• comprising a compound ZINC04307500 having the structure:
• and
• (b) administering the pharmaceutical compound, formulation or composition of (a) to the cell or, inserting the pharmaceutical compound or composition into the cell, in an amount sufficient to stabilize the F-actin polymer, actin filament, or actin-comprising microtubule;
• or
• (ii) the method of (i), wherein the administering of the pharmaceutical compound, formulation or composition to the cell is in vitro, ex vivo or in vivo.

A method for decreasing cell motility, comprising:

• (i) (a) providing a pharmaceutical, formulation or composition
• comprising a compound ZINC04307500 having the structure:
• or any analog or derivative thereof or a stereoisomer or a bioisostere thereof;
• and
• (b) administering the pharmaceutical compound, formulation or composition of (a) to the cell or, inserting the pharmaceutical compound or composition into the cell, in an amount sufficient to decrease the cell's motility;
• or
• (ii) the method of (i), wherein the administering of the pharmaceutical compound, formulation or composition to the cell is in vitro, ex vivo or in vivo.

A method for decreasing cell motility, comprising:

• (i) (a) providing a pharmaceutical, formulation or composition
• comprising a compound ZINC04307500 having the structure:
• and
• (b) administering the pharmaceutical compound, formulation or composition of (a) to the cell or, inserting the pharmaceutical compound or composition into the cell in an amount sufficient to decrease the cell's motility;
• or
• (ii) the method of (i), wherein the administering of the pharmaceutical compound, formulation or composition to the cell is in vitro, ex vivo or in vivo.

A method for ameliorating a disease or condition responsive to inhibiting or decreasing cell motility and/or stabilizing F-actin polymers, actin filaments, or actin-comprising microtubules in a cell, comprising:

• (i) (a) providing a pharmaceutical, formulation or composition
• comprising a compound ZINC04307500 having the structure:
• or any analog or derivative thereof or a stereoisomer or a bioisostere thereof;
• and
• (b) administering the pharmaceutical compound, formulation or composition of (a) to an individual in need thereof in an amount sufficient to inhibit or decrease cell motility and/or stabilize F-actin polymers, actin filaments, or actin-comprising microtubules;
• or
• (ii) the method of (i), wherein disease or condition ameliorated is cancer, a metastasis.

A method for ameliorating a disease or condition responsive to inhibiting or decreasing cell motility and/or stabilizing F-actin polymers, actin filaments, or actin-comprising microtubules in a cell, comprising:

• (i) (a) providing a pharmaceutical, formulation or composition
• comprising a compound ZINC04307500 having the structure:
• or any analog or derivative thereof or a stereoisomer or a bioisostere thereof;
• and
• (b) administering the pharmaceutical compound, formulation or composition of (a) to an individual in need thereof in an amount sufficient to inhibit or decrease cell motility and/or stabilize F-actin polymers, actin filaments, or actin-comprising microtubules;
• or
• (ii) the method of (i), wherein disease or condition ameliorated is Alzheimer's disease.

A method for decreasing or inhibiting cell growth, comprising:

• (i) (a) providing a pharmaceutical, formulation or composition
• comprising a compound ZINC04307500 having the structure:
• or any analog or derivative thereof or a stereoisomer or a bioisostere thereof;
• and
• (b) administering the pharmaceutical compound, formulation or composition of (a) to the cell or;
• inserting the pharmaceutical compound or composition into the cell, in an amount sufficient to decrease or inhibit cell growth;
• or
• (ii) the method of (i), wherein the administering of the pharmaceutical compound, formulation or composition to the cell is in vitro, ex viva or in vivo.

A method for decreasing or inhibiting cell growth, comprising:

• (i) (a) providing a pharmaceutical, formulation or composition
• comprising a compound ZINC04307500 having the structure:
• and
• (b) administering the pharmaceutical compound, formulation or composition of (a) to the cell or, inserting the pharmaceutical compound or composition into the cell, in an amount sufficient to decrease or inhibit cell growth;
• or
• (ii) the method of (i), wherein the administering of the pharmaceutical compound, formulation or composition to the cell is in vitro, ex vivo or in viva.