Repositioning Candidate Details
| Candidate ID: | R1560 |
| Source ID: | DB15442 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Trilaciclib |
| Synonyms: | Trilaciclib |
| Molecular Formula: | C24H30N8O |
| SMILES: | CN1CCN(CC1)C1=CN=C(NC2=NC3=C(C=C4N3C3(CCCCC3)CNC4=O)C=N2)C=C1 |
| Structure: |
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| DrugBank Description: | Trilaciclib, or G1T28, is a CDK4 and CDK6 inhibitor, indicated to reduce the incidence of chemotherapy induced myelosuppression in patients before topotecan-containing or platinum and etoposide-containing chemotherapy for extensive stage small cell lung cancer. CDK4 and CDK6 inhibitors have been investigated since the mid 1990s for their use in tumorigenesis and chemotherapy. Trilaciclib was first described in the literature in 2016. Trilaciclib was granted FDA approval on 12 February 2021. |
| CAS Number: | 1374743-00-6 |
| Molecular Weight: | 446.559 |
| DrugBank Indication: | Trilaciclib is indicated to reduce the incidence of chemotherapy induced myelosuppression in patients prior to receiving platinum and etoposide-containing or topotecan-containing chemotherapy regimens for extensive-stage small cell lung cancer. |
| DrugBank Pharmacology: | Trilaciclib is indicated to reduce the incidence of chemotherapy induced myelosuppression in patients prior to receiving platinum and etoposide-containing or topotecan-containing chemotherapy regimens for extensive-stage small cell lung cancer. It has a short duration of action of approximately 16 hours, and a narrow therapeutic index. Patients should be counselled regarding the risk of injection site reactions, hypersensitivity, and interstitial lung disease. |
| DrugBank MoA: | Trilaciclib is inhibits cyclin-dependant kinase 4 (CDK4) at a concentration of 1 nmol/L and cyclin-dependent kinase 5 (CDK5) at 4 nmol/L. Inhibition of CDK2, CDK5, and CDK7 is over 1000-fold less at these concentrations and inhibition of CDK9 is 50-fold less. CDK4 and CDK5 are expressed in hematopoietic stem cells and progenitor cells. They are capable of phosphorylating and inactivating the retinoblastoma protien; a tumor suppressor. When trilaciclib is given to patients with retinoblastoma protein-null small cell lung cancer, it does not interfere with the intended chemotherapy induced cytotoxicity of cancer cells. Inhibition of CDK4 and CDK5 leads to a reversible pause in the cell cycle in the G1 phase for approximately 16 hours. The temporary cell cycle arrest prevents chemotherapy induced DNA damage in healthy cells, reducing the activity of caspases 3 and 7, which reduces apoptosis of healthy cells. Other studies have shown inhibitors of CDK4 and CDK6 enhance T-cell activation, upregulating major histocompatibility complex (MHC) class I and II, and stabilize programmed death-ligand 1 (PD-L1). Together these activities increase T-cell activity, increase antigen presentation, and sensitize cells to immune checkpoint inhibitors. |
| Targets: | Cyclin-dependent kinase 4 inhibitor; Cyclin-dependent kinase 6 inhibitor; Cyclin-dependent kinase 9 inhibitor; Cyclin-dependent kinase 2 inhibitor; Cyclin-dependent kinase 5 inhibitor; Cyclin-dependent kinase 7 inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
