Table 5.
Inhibitors of MEK/PI3K/STAT3
| Pathway | Name | Target | Clinical trial | Cancers | References |
|---|---|---|---|---|---|
| MAPK | PD098059 | MEK1/2 | Preclinical | Advanced hematological and advanced solid cancers | [101–104] |
| U0126 | MEK1/2 | Preclinical | Advanced hematological and advanced solid cancers | [103–105, 107, 108] | |
| AZD8330 | MEK1/2 | Phase I | Advanced solid tumors | [109] | |
| E6201 | MEK1 | Phase I | Melanoma | [99, 110, 111] | |
| PD-0325901 | MEK1/2 | Phase I | Melanoma, NSCLC | [110, 112, 113] | |
| Pimasertib (AST03026) | MEK1/2 | Phase I | Colorectal, multiple myeloma | [115] | |
| RO4987655 | MEK1 | Phase I | Melanoma | [116] | |
| RO5126766 | Raf/MEKl/2 | Phase I | Melanoma | [117] | |
| TAK733 | MEK1/2 | Phase I | Melanoma, NSCLC, colorectal, breast | [114, 118] | |
| MEK162 | MEK1/2 | Phase I/II | NRAS mutant melanoma, NSCLC, pancreatic, BTC | [119] | |
| Selumetinib (AZD6244) | MEK1 | Phase I, II | Melanoma HCC, pancreatic, colon, lung, breast, NSCLC | [120–133] | |
| Refametinib (RDEA119) | MEK1/2 | Phase II | HCC, melanoma, colorectal | [95] | |
| WX-554 | MEK1/2 | Phase II | Advanced solid tumors | [95] | |
| Trametinib (GSK1120212) | MEK1/2 | Phase III | Melanoma, colorectal | [134] | |
| Cobimetinib (GDC-0973) | MEK1 | Phase I, II, III | Advanced solid tumors, melanoma | [135–138] | |
| PI3K | LY294002 | PI3K and other related kinases | Preclinical | Fibrosarcoma | [105, 107, 139–141] |
| PI-103 | PI3K, mTORC1/2, DNA-PK | Preclinical | Glioma prostate, colon, NSCLC | [142–146] | |
| PWT-458 | PI3K | Preclinical | NSCLC, glioblastoma, renal | [147, 148] | |
| Wortmannin | PI3K, mTOR, DNA-PK, MAPK | Preclinical | Advanced hematological and advanced solid cancers | [135, 142, 149] | |
| ZSTK474 | PI3Ks | Preclinical | NSCLC, melanoma, ovarian, prostate | [150, 151] | |
| BAY 80–6946 | PI3K(p110α, p) | Phase I | Lymphoma, esophageal, pancreatic | [135] | |
| GDC-0032 | PI3K(pl00α,-δ,-γ) | Phase I | Breast, NSCLC | [135] | |
| GSK-2126458 | PI3K, mTOR | Phase I | Renal cell, bladder | [152] | |
| IPI-145 | PI3K(p110 δ, γ) | Phase I | Leukemia, lymphoma | [135] | |
| BEZ-235 | PI3K, mTOR | Phase I, II | Breast, glioma, melanoma, pancreatic | [135, 153–156] | |
| BGT-226 | PI3K, mTOR | Phase I/II | Solid tumors, breast | [157] | |
| BKM120 (Buparlisib) | PI3K | Phase I/II | Breast, glioblastoma, NSCLC | [135,158] | |
| BYL-719 | PBK(p110 α) | Phase I/II | Breast, cervical, ovarian, head and neck | [135] | |
| GDC-0941 | PI3K(p110α),Flt3 | Phase I/II | Lymphoma, NSCLC, breast, melanoma, pancreatic endometrial | [135, 159–161] | |
| GDC-0980 | PI3K, mTOR | Phase I/II | Prostate | [135] | |
| PX-866 | PI3K | Phase I/II | Glioblastoma, breast, colon, prostate, NSCLC, pancreatic, ovarian | [135, 162, 163] | |
| XL-147 | PI3K | Phase I/II | NSCLC, solid tumors, glioblastoma | [96, 135] | |
| XL-765 | PI3K, mTOR | Phase I/II | Glioma, NSCLC | [164] | |
| PF-04691502 | PI3K, mTOR | Phase II | Endometrial | [135] | |
| PF-05212384 | PI3K(p110 α, γ), mTOR | Phase II | Solid tumors, colon | [135] | |
| CAL-101 (Idelalisib) | PI3K(p110δ) | Phase III | Leukemias, lymphomas, myeloma | [135] | |
| STAT3 | OPB-31121 | STAT3 | Phase I | Advanced HCC | [165] |
| AZD9150 | STAT3 | Phase I/II | Lymphoma, HCC, ovarian, GI | , , , , [166] |
|
| BBI6018 (napabucasin) | STAT3 | Phase I/II/III | Hematologic malignancies, colorectal, GI, pancreatic, HCC, glioblastoma, NSCLC, mesothelioma, | , , , , , , , , , , , , , , , |
BTC - biliary tract cancer, DNA-PK - DNA-dependent protein kinase, Flt3 - Fms-related tyrosine kinase 3, GI - gastrointestinal, HCC - hepatocellular carcinoma, MEK - extracellular signal-regulated kinase (ERK) kinase, mTOR - mammalian target of rapamycin, NSCLC – non-small cell lung cancer,PI3K - phosphoinositide 3-kinase, STAT3 - signal transducer and activator of transcription 3