The clinical study status and kinase activity of representative MEK inhibitors
| MEK inhibitor | Target | Kinase activity (IC50) | Clinical phase | Tumors | Obstacles | Ref |
| CI-1040 | MEK1/2 | 2.3 nmol/L | Phase II | Breast cancer, CRC, NSCLC, pancreatic cancer | Poor pharmacokinetic properties such as low bioavailability and rapid metabolism | 55 |
| Trametinib | MEK1/2 | 0.7/0.9 nmol/L | FDA approved | Melanoma, CRC, NSCLC, biliary cancer, papillary thyroid carcinoma | Rash, diarrhea, peripheral edema | 57 |
| Cobimetinib | MEK1 | 0.9 nmol/L | FDA approved | Melanoma, leukemia, CRC | Rash, pyrexia, chorioretinopathy, gastrointestinal disorders | 58 |
| Binimetinib | MEK1/2 | 12 nmol/L | FDA approved | Melanoma | Rash, nausea, vomiting, diarrhea, peripheral edema, fatigue | 60 |
| PD-0325901 | MEK1/2 | 0.33 nmol/L | FDA approved | NF1, NSCLC, CRC, melanoma, breast cancer | Musculoskeletal, neurological, ocular toxicity | 61 |
| Selumetinib (AZD6244) | MEK1 | 14 nmol/L | Phase III | NSCLC, melanoma, CRC, HCC, glioma, NF1, PA | Rash, diarrhea, nausea, fatigue, blurred vision | 63 |
| Refametinib | MEK1/2 | 19/47 nmol/L | Phase II | HCC, CRC, melanoma, pancreatic cancer | Dermatological, gastrointestinal and ocular toxicity, low tolerance | 64 |
| Pimasertib | MEK1/2 | 5-11 nmol/L | Phase II | Ovarian cancer, melanoma, breast cancer, NSCLC, HCC, CRC, pancreatic cancer | Diarrhea, fatigue, nausea, ocular toxicity | 65 |
| RO4987655 | MEK1/2 | 5.2 nmol/L | Phase I | Melanoma, NSCLC, CRC | Gastrointestinal and eye disorders, skin and CNS-related toxicity | 66 |
| AZD8330 | MEK1/2 | 7 nmol/L | Phase I | Melanoma | Mental status changes, acneiform dermatitis, fatigue, diarrhea, vomiting | 67 |
| TAK-733 | MEK1/2 | 3.2 nmol/L | Phase I | Melanoma, CRC, NSCLC, pancreatic cancer, breast cancer | Rash, diarrhea, increased blood CPK | 68 |
| WX-554 | MEK1/2 | 4.7/11 nmol/L | Phase I | Cervical cancer, ampullary cancer, CRC | Poor tolerability, drug toxicity | 69 |
| RO5126766 | MEK1/2 | 160 nmol/L | Phase I | Melanoma, CRC | Rash, diarrhea, acneiform dermatitis, elevated CPK, blurred vision | 70 |
| GDC-0623 | MEK1/2 | 0.13 nmol/L | Phase I | Melanoma, NSCLC, pancreatic cancer | | 71 |
| HL-085 | MEK1 | 1.9-10 nmol/L | Phase I | Melanoma, CRC | | 7 |
| RO5068760 | MEK1 | 25±12 nmol/L | Preclinical | Melanoma, CRC, lymphoma, pancreatic cancer | No apparent toxicity in tumor cells and xenografts. | 72 |
| RO4927350 | MEK1/2 | 23 nmol/L | Preclinical | A broad spectrum of RAS or BRAF-mutant cancers | No apparent toxicity in tumor cells and xenografts. | 73 |
| PD184161 | MEK | 10-100 nmol/L | Preclinical | HCC | No apparent toxicity in tumor cells and xenografts. | 74 |
| PD098059 | MEK1 | 2 mol/L | Preclinical | NSCLC, bronchoepithelial inflammation | No apparent toxicity in tumor cells and xenografts. | 75 |
| U0126 | MEK1/2 | 70/60 nmol/L | Preclinical | Cervical cancer, CRC, HCC, embryonal rhabdomyosarcoma, glioblastoma, pancreatic cancer | No apparent toxicity in tumor cells and xenografts. | 76 |
| SL327 | MEK1/2 | 0.18/0.22 mol/L | Preclinical | ATC | | 77 |
| CInQ-03 | MEK1/2 | 5/10 mol/L | Preclinical | CRC | | 78 |
| G-573 | MEK | 406 nmol/L | Preclinical | CRC, NSCLC | | 79 |
| PD318088 | MEK1 | | Preclinical | Leukemia | | 80 |
PA, pilocytic astrocytomas; CNS, central nervous system.