Table 1.
Examples of small-molecular inhibitor targeting Akt and its downstream effectors for human cancer therapy
| Name | Target | Effect | Tumor | Clinical trail |
|---|---|---|---|---|
| Uprosertib (GSK2141795) | Akt1/2/3 | ATP-competitive pan-Akt inhibitor | Endometrial carcinoma; myeloma; melanoma; hematopoietic and lymphoid cell neoplasm; malignant solid neoplasm | Phase I/II |
| Capivasertib (AZD5363) | Akt1/2/3;P70S6K/PKA | ATP-competitive pan-Akt inhibitor | B-cell non-hodgkin lymphoma; breast; prostate; solid and hematological tumors | Phase I/II/III |
| Ipatasertib (GDC-0068) | Akt1/2/3 | ATP-competitive pan-Akt inhibitor | Breast; head and neck carcinoma; solid tumors; gastric; prostate; ovarian; NSCLC | Phase I/II/III |
| Afuresertib (GSK2110183) | Akt1/2/3 | ATP-competitive pan-Akt inhibitor | Breast; prostate; ovarian; solid tumors | Phase I/II |
| GSK690693 | Akt1/2/3;PKA, PrkX, PKC | ATP-competitive pan-Akt inhibitor | Hematologic malignancies; solid tumors; lymphoma | Phase I |
| LY2780301 | Akt1/2/3;P70S6K | ATP-competitive pan-Akt inhibitor | Breast; solid tumors; non-Hodgkin’s lymphoma; metastatic cancers | Phase I/II |
| Perifosine (KRX-0401) | Akt1/2 | Allosteric Akt inhibitor | Brain; prostate; pancreatic; melanoma; renal cell carcinoma; breast; NSCLC; myeloma; solid tumors | Phase I/II |
| MK-2206 | Akt1/2/3 | Allosteric Akt inhibitor | Solid tumors; lymphomas; breast; colorectal; gall bladder; melanoma; nsclc; oral; ovarian; pancreatic; prostate | Phase I/II |
| Miransertib (ARQ 092) | Akt1/2/3 | Allosteric Akt inhibitor | Proteus syndrome; solid tumors; lymphomas; ovarian; endometrial | Phase I/II |
| ARQ 751 | Akt1/2/3 | Allosteric Akt inhibitor | Solid tumors | Phase I |
| TAS117 | Akt1/2/3 | Allosteric Akt inhibitor | Solid tumors | Phase II |
| BAY1125976 | Akt1/2 | Allosteric Akt inhibitor | Neoplasms | Phase I |
| PHT427 | Akt1/2/3 | Allosteric Akt inhibitor | NA | NA |
| Akti-1/2 | Akt1/2 | Allosteric Akt inhibitor | NA | NA |
| Solenopsin | Akt | An alkaloid component of fire ant venom | NA | NA |
| Rapamycin; rapaloges | mTORC1 | Allosteric mTORC1 inhibitor | Bladder; pancreatic; solid tumors; lymphoma; leukemia; prostate; brain; NSCLC | Phase I/II |
| PP242 | mTORC1/C2 | Inhibiting mTOR and eIF4E activation | NA | NA |
| Compound A | Skp2 | Inhibiting Skp2 SCF E3 ligase activity to prevent p27 ubiquitination and degradation | NA | NA |
| Compound 25 | Skp2 | Preventing the assembly of newly synthesized Skp2-Skp1 complex by binding to Skp2 to inactivate its E3 ligase activity | NA | NA |
| Pevonedistat (MLN4924) | Nedd8-activating enzyme | Inhibiting neddylation of Cul-1 and the formation Skp2 SCF complex | Leukemia; myeloma; melanoma; solid tumors | Phase I/II |
| Nutlin-3 | Mdm2 | Occupation of the binding site of p53 in MDM2 | NA | NA |
| HBX41108 | USP7 | Targeting USP7 to prevent MDM2 deubiquitination and promote MDM2 degradation | NA | NA |
NA: not applicable