Repositioning Candidate Details
| Candidate ID: | R1058 |
| Source ID: | DB06606 |
| Source Type: | investigational |
| Compound Type: | biotech |
| Compound Name: | Teplizumab |
| Synonyms: | Teplizumab |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | Type 1 diabetes (T1D) is an autoimmune condition in which T cell-mediated destruction of pancreatic β cells leads to loss of insulin production, impaired glycemic control, and reliance on exogenous insulin. Targeting T cells can be achieved through antibodies against the T cell receptor (TCR) component CD3 ε. However, if Fc binding is left intact, severe adverse effects related to cytokine release syndrome (CRS) are observed, and therefore Fc-nonbinding antibodies are the preferred method of choice. Anti-CD3 therapy has traditionally been used to prevent graft-versus-host-disease in organ transplantation but more recently has been explored to prolong the onset of (T1D) in high-risk patients. Teplizumab is a humanized IgG1κ Fc-nonbinding anti-CD3 monoclonal antibody currently under development for use in T1D. |
| CAS Number: | 876387-05-2 |
| Molecular Weight: | |
| DrugBank Indication: | Investigated for use/treatment in diabetes mellitus type 1. |
| DrugBank Pharmacology: | -- |
| DrugBank MoA: | Type 1 diabetes (T1D) is an autoimmune condition in which T cell-mediated destruction of pancreatic β cells leads to loss of insulin production, impaired glycemic control, and reliance on exogenous insulin. T1D is a progressive disease with three recognizable stages and in which only Stage 3 is associated with clinically apparent symptoms. The earliest indication of T1D risk is the presence of at least two autoantibodies against relevant antigens, confirming an important role for B cells in what has traditionally been considered a T cell-dominated condition. Combined with other observations from animal and human studies, it is clear that the T-B axis plays a role in T1D; treatment has focussed on targeting B and T cells independently, as well as their interactions. The T cell receptor (TCR) comprises TCR α and β chains together with six CD3 molecules, including two CD3 ε chains. It is responsible for recognizing antigens displayed on the MHC complex of other cells to elicit a response. Teplizumab, a humanized IgG1κ Fc-nonbinding version of an existing mouse OKT3 antibody (also designated huOKT3γala-ala), is specific for CD3 ε and inhibits T cell activation through steric inhibition of antigen recognition. Recently, teplizumab has shown efficacy in delaying the time to diagnosis in patients at high risk of developing T1D. However, the exact mechanism underlying this effect remains clear. One hypothesis is that teplizumab acts as a partial agonist at the TCR, increasing the number of exhausted T cells positive for KLRG1, TIGIT, and CD8. These exhausted T cells persist but cannot perform effector functions and, therefore, would be unlikely to contribute to further β cell destruction. Other studies have noted changes in the T cell populations of clinical responders, including an increase in circulating CD8<sup>+</sup> central memory (CD8CM) T cells. It is clear, however, that treatment is most effective in patients who have very recently or not yet progressed to Stage 3 and who have an active immune response. |
| Targets: | T-cell surface glycoprotein CD3 epsilon chain antagonist |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |