An in vitro method of inducing a non-pluripotent human cell into an induced pluripotent stem cell, the method comprising: (a) contacting the non-pluripotent human cell with an Oct4 polypeptide or introducing into the non-pluripotent human cell a polynucleotide encoding an Oct4 polypeptide; and (b) contacting the non-pluripotent human cell with a small molecule TGFβ receptor/ALK5 inhibitor, a small molecule MEK inhibitor, a small molecule histone deacetylase (HDAC) inhibitor, and an allosteric small molecule 3'-phosphoinositide-dependent kinase-1 (PDKl) activator under conditions sufficient to induce the non-pluripotent human cell to become a pluripotent stem cell, thereby inducing the non-pluripotent human cell into an induced pluripotent stem cell; or (a) contacting the non-pluripotent human cell with an Oct4 polypeptide and a Klf4 polypeptide or introducing into the non-pluripotent human cell a polynucleotide encoding an Oct4 polypeptide and a polynucleotide encoding a Klf4 polypeptide; and (b) contacting the non-pluripotent human cell with a small molecule TGFβ receptor/ALK5 inhibitor, a small molecule MEK inhibitor, and an allosteric small molecule 3'-phosphoinositide-dependent kinase-1 (PDKl) activator under conditions sufficient to induce the non-pluripotent human cell to become a pluripotent stem cell, thereby inducing the non-pluripotent human cell into an induced pluripotent stem cell. (a) contacting the non-pluripotent human cell with an Oct4 polypeptide or introducing into the non-pluripotent human cell a polynucleotide encoding an Oct4 polypeptide; and (b) contacting the non-pluripotent human cell with a small molecule TGFβ receptor/ALK5 inhibitor, a small molecule MEK inhibitor, a small molecule histone deacetylase (HDAC) inhibitor, and an allosteric small molecule 3'-phosphoinositide-dependent kinase-1 (PDKl) activator under conditions sufficient to induce the non-pluripotent human cell to become a pluripotent stem cell, thereby inducing the non-pluripotent human cell into an induced pluripotent stem cell; or (a) contacting the non-pluripotent human cell with an Oct4 polypeptide or introducing into the non-pluripotent human cell a polynucleotide encoding an Oct4 polypeptide; and (b) contacting the non-pluripotent human cell with a small molecule TGFβ receptor/ALK5 inhibitor, a small molecule MEK inhibitor, a small molecule histone deacetylase (HDAC) inhibitor, and an allosteric small molecule 3'-phosphoinositide-dependent kinase-1 (PDKl) activator under conditions sufficient to induce the non-pluripotent human cell to become a pluripotent stem cell, thereby inducing the non-pluripotent human cell into an induced pluripotent stem cell; or (a) contacting the non-pluripotent human cell with an Oct4 polypeptide and a Klf4 polypeptide or introducing into the non-pluripotent human cell a polynucleotide encoding an Oct4 polypeptide and a polynucleotide encoding a Klf4 polypeptide; and (b) contacting the non-pluripotent human cell with a small molecule TGFβ receptor/ALK5 inhibitor, a small molecule MEK inhibitor, and an allosteric small molecule 3'-phosphoinositide-dependent kinase-1 (PDKl) activator under conditions sufficient to induce the non-pluripotent human cell to become a pluripotent stem cell, thereby inducing the non-pluripotent human cell into an induced pluripotent stem cell. (a) contacting the non-pluripotent human cell with an Oct4 polypeptide and a Klf4 polypeptide or introducing into the non-pluripotent human cell a polynucleotide encoding an Oct4 polypeptide and a polynucleotide encoding a Klf4 polypeptide; and (b) contacting the non-pluripotent human cell with a small molecule TGFβ receptor/ALK5 inhibitor, a small molecule MEK inhibitor, and an allosteric small molecule 3'-phosphoinositide-dependent kinase-1 (PDKl) activator under conditions sufficient to induce the non-pluripotent human cell to become a pluripotent stem cell, thereby inducing the non-pluripotent human cell into an induced pluripotent stem cell.