Table 1.
Replication stress targets in preclinical development and clinical trials.
| Target Protein | Inhibitor | Recent/Ongoing Clinical Trials * | Tumor/Cell Targets ** | References |
|---|---|---|---|---|
| Chk1/Chk2 | UCN-01 | Solid tumors, leukemia | [116] | |
| LY2603618 | NCT01341457 | Solid tumors | [117] | |
| GDC-0575 | NCT01564251 | Solid tumors, lymphoma | [118] | |
| MK-8776 | NCT01870596 | Acute myeloid leukemia | [119] | |
| NCT00779584 | Solid tumors, lymphoma | |||
| LY2606368 | NCT02735980 | Lung cancer | [120] | |
| NCT02778126 | Solid/CNS tumors | [121] | ||
| NCT02203513 | TNBC | [122] | ||
| NCT01115790 | Advanced solid tumors | [123] | ||
| Wee1 | MK1775 | NCT01357161 | Ovarian cancer | [124] |
| ATR | BAY1895344 | NCT03188965 | Advanced solid tumors | [125] |
| AZD6738 | NCT02264678 | Advanced solid tumors | [126] | |
| TopBP1 | Calcein AM | Breast, lung xenografts | [127,128] | |
| CtIP | SP(18–28) | Breast cancer cells | [129] | |
| PACMP | siRNA-lnc15.2 | Breast, ovarian, lung, OS, stomach cancer cells | [130] | |
| MUS81 | siRNA-MUS81 | Gastric cancer cells | [131] | |
| EEPD1 | siRNA-MUS81 | Lung, OS, fibrosarcoma, cervical cancer cells | [103,104] | |
| Metnase | Ciprofloxacin | Embryonic kidney cells | [132] | |
| RAD51 | RI-1 | Glioblastoma, glioma cells | [133,134,135] | |
| B02 | Glioblastoma, multiple myeloma cells | [135,136] | ||
| PARP1 | Olaparib | NCT03531840 | Mesothelioma | [137] |
| NCT03402841 | Ovarian cancer | [138] | ||
| NCT03286842 | Breast cancer | [139] | ||
| NCT02983799 | Ovarian cancer | [140] | ||
| NCT02789332 | Breast cancer | [141] | ||
| NCT02734004 | Breast cancer | [142] | ||
| NCT02477644 | Ovarian cancer | [143] | ||
| NCT01513174 | Lung cancer | [144] | ||
| NCT02282020 | Ovarian cancer | [145] | ||
| Rucaparib | NCT02952534 | Prostate cancer | [146] | |
| NCT02042378 | Pancreatic cancer | [147] | ||
| NCT01891344 | Ovarian cancer | [148] | ||
| NCT01074970 | Ovarian, solid tumors | [149] | ||
| NCT01891344 | Ovarian cancer | [150] | ||
| Niraparib | NCT03759600 | Ovarian cancer | [151] | |
| NCT04475939 | Lung cancer | [152] | ||
| NCT02657889 | TNBC | [153] | ||
| NCT02354131 | Ovarian cancer | [154] | ||
| NCT02354586 | Ovarian cancer | [155] | ||
| ATM | AZD0156 | NCT02588105 | Advanced solid tumors | [156] |
| ATM/ATR | AZD1390 | NCT03215381 | Healthy volunteers | [156] |
* Clinical trials ongoing (actively enrolling) or completed since 2015. Most trials include combination therapies with the indicated inhibitor. For PARP1i, only completed Phase II/III trials with peer-reviewed publications since 2015 are listed: data from ClinicalTrials.gov. Several recent reviews provide additional information about the numerous PARP1i clinical trials [157,158,159,160,161,162,163]. ** CNS, central nervous system; TNBC, triple negative breast cancer; OS, osteosarcoma.