Repositioning Candidate Details
| Candidate ID: | R1395 |
| Source ID: | DB11714 |
| Source Type: | approved; investigational |
| Compound Type: | biotech |
| Compound Name: | Durvalumab |
| Synonyms: | Durvalumab |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody and a novel immune-checkpoint inhibitor for cancer treatment. Produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cell suspension culture, durvalumab is a programmed death-ligand 1 (PD-L1) blocking antibody that works to promote normal immune responses that attack tumour cells. Durvalumab is marketed under the brand name Imfinzi, which is available for intravenous injections. It was granted accelerated approval by the FDA in May 2017 for the treatment of selected patients with locally advanced or metastatic urothelial carcinoma. In September 2018, durvalumab was approved by the EMA for the treatment of adult patients with locally advanced, unresectable non-small cell lung cancer (NSCLC), only if PD-L1 is expressed in ≥ 1% of tumour cells and there was no observable disease progression following platinum-based chemoradiation therapy. On March 27, 2020, durvalumab was approved by the FDA for use in combination with and either or as first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). |
| CAS Number: | 1428935-60-7 |
| Molecular Weight: | |
| DrugBank Indication: | Durvalumab is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Durvalumab is indicated for the treatment of patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. It is also approved for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) in combination with and either or as first-line therapy. Durvalumab is indicated as monotherapy used for the treatment of locally advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on ≥ 1% of tumour cells and whose disease has not progressed following platinum-based chemoradiation therapy. |
| DrugBank Pharmacology: | Durvalumab is an anticancer antibody that works to promote the antitumour responses mediated by immune cells. By blocking the action of PD-L1, durvalumab exerts its anticancer effects by increasing T-cell activation, enhancing detection and ablation of tumour cells. In _in vitro_ assays, durvalumab inhibited the activity of PD-L1 in a concentration-dependent manner. In co-engrafted human tumor and immune cell xenograft mouse models, durvalumab was effective in decreasing tumour size. Durvalumab does not mediate antibody-dependent cell-mediated cytotoxicity (ADCC). |
| DrugBank MoA: | Because cancer cells express antigens that are recognized and taken up by antigen-presenting cells (APCs), the immune responses prime and activate cytotoxic T cells, and allow them to travel to the site of tumour to destroy cancer cells. However, tumours often evade T cell-mediated immune responses to enhance their survival. Inflammatory mediators, such as IFN-gamma, induce the expression of programmed cell death ligand-1 (PD-L1), which is a type 1 transmembrane protein expressed on tumour cells and tumour-associated immune cells in the tumour microenvironment. PD-L1 acts as an immune checkpoint to regulate immune responses. PD-L1 is a ligand to PD-1, which is a cell surface receptor expressed on activated T cells in peripheral tissues following antigen exposure. Both PD-L1 and PD-1 are co-inhibitory molecules involved in blocking T cell-mediated immune responses. PD-L1 also interacts with CD-80, which is a receptor constitutively expressed by T cells and is upregulated early after T cell activation. The expression of PD-L1 is an adaptive immune response by tumour cells, resulting in over-expression of the molecule in some cancers. PD-L1 interacts with PD-1 and CD80, which leads to blocked cytotoxic T cell activation, T cell proliferation, and cytokine production. By binding to PD-L1 and preventing its association with PD-1 and CD80, durvalumab activates the immune responses mediated by cytotoxic T cells that attack tumour cells. Durvalumab displays selective and high affinity toward PD-L1 but not PD-L2, which is a regulatory ligand expressed in tumour cells to a lesser extent and involved in regulating inflammation and differentiation of T cells. |
| Targets: | Programmed cell death 1 ligand 1 inhibitor&antibody |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|