Table 2.
Current status of transcription associated CDK inhibitors in clinical trials.
| Name(s) | Inhibitor Type | Intended Therapeutic Target | Major Biologial Target(s) IC50 (nM)* | Company | Malignancy Type(s) | Clinical Trial Status |
|---|---|---|---|---|---|---|
| CT7001 (ICEC0942, Samuraciclib) | Non-covalent | CDK7 | CDK1 = 1800; CDK2 = 620; CDK4 = 49000; CDK5 = 9400; CDK6 = 34000; CDK7 = 40; CDK9 = 1200 | Carrick Therapeutics | Advanced Solid Malignancies |
Phase I/II NCT03363893 (Active) |
| Hoffmann-La Roche | Locally Advanced or Metastatic ER-positive Breast Cancer |
Phase I/II NCT04802759 (Recruiting) |
||||
| SY-1365 | Covalent | CDK7 | CDK7 = 20 | Syros Pharmaceuticals | Advanced Solid Tumours |
Phase I NCT03134638 (Terminated) |
| SY-5609 | Non-covalent | CDK7 | CDK2 = 2900†;CDK7 = 0.06#; CDK9 = 970†; CDK12 = 770† | Syros Pharmaceuticals | Advanced Solid Tumours |
Phase I NCT04247126 (Recruiting) |
| XL102 (AUR102) | Covalent | CDK7 | Not disclosed | Exelixis | Advanced Solid Tumours |
Phase I NCT04726332 (Recruiting) |
| LY3405105 | – | CDK7 | CDK1 = 20000; CDK2 = 20000; CDK4 = 2830; CDK6 = 8079; CDK7 = 92.8; CDK9 = 6200; CDK12 = 14780 | Eli Lilly and Company | Advanced Solid Tumours |
Phase I NCT03770494 (Terminated) |
| BAY1143572 | Non-covalent | CDK9 | CDK9 = 13; CDK3 = 890; CDK2 = 1000; CDK1 = 1100; CDK5 = 1600 | Bayer | Advanced Acute Leukaemia |
Phase I NCT02345382 (Completed) |
| Advanced Malignancies |
Phase I NCT01938638 (Completed) |
|||||
| VIP152 (BAY1251152) | Non-covalent | CDK9 | CDK2 = 360; CDK9 = 3 | Vincerx Pharma | Advanced Hematological Malignancies |
Phase I NCT02745743 (Completed) |
| Advanced Solid Tumours and Aggressive Non-Hodgkin’s Lymphoma |
Phase I NCT02635672 (Recruiting) |
|||||
| Relapsed/Refractory Chronic Lymphocytic Leukemia or Richter Syndrome |
Phase I NCT04978779 (Recruiting) |
|||||
| AZD4573 | Non-covalent | CDK9 | CDK9 = < 4 | AstraZeneca | Relapsed/Refractory Haematological Malignances |
Phase I NCT03263637 (Completed) |
|
Phase I/II NCT04630756 (Recruiting) |
||||||
| Relapsed/Refractory Peripheral T-cell Lymphoma or Classical Hodgkin Lymphoma |
Phase II NCT05140382 (Not Yet Recruiting) |
|||||
| KB-0742 | Non-covalent | CDK9 | CDK9 = 6 | Kronos Bio | Relapsed or Refractory Solid Tumors; Non-Hodgkin Lymphoma |
Phase I NCT04718675 (Recruiting) |
| GFH009 | Not disclosed | CDK9 | Not disclosed | GenFleet Therapeutics | Relapsed/Refractory hematologic malignancies |
Phase 1 NCT04588922 (Recruiting) |
| BCD-115 (Senexin B) | Non-covalent | CDK8/19 | CDK8 = 17.3; CDK19 = 4.2 | Biocad | Locally Advanced or Metastatic ER-positive HER2-negative Breast Cancer |
Phase 1 NCT03065010 (Completed) |
| RVU120 (SEL120) | Covalent | CDK8/19 | CDK8 = 4.4; CDK19 = 10.4 | Ryvu Therapeutics | Acute Myeloid Leukemia;High-risk Myelodysplastic Syndrome |
Phase I NCT04021368 (Recruting) |
| Metastatic or Advanced Solid Tumours |
Phase I/II NCT05052255 (Recruting) |
*IC50 data has been listed for CDK1, 2, 3, 4, 6, 7, 9, and 12 derived from in vitro kinase activity, where available. Data has been omitted from the table if undisclosed or not applicable. †Kd determined by surface plasmon resonance. #Ki determined by activity assay.
CDK cyclin-dependent kinase, ER Oestrogen receptor.