Repositioning Candidate Details
| Candidate ID: | R1377 |
| Source ID: | DB11581 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Venetoclax |
| Synonyms: | 4-{4-[(4'-chloro-5,5-dimethyl[3,4,5,6-tetrahydro[1,1'-biphenyl]]-2-yl)methyl]piperazin-1-yl}-N-(3-nitro-4-{[(oxan-4-yl)methyl]amino}benzene-1-sulfonyl)-2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]benzamide; Venetoclax |
| Molecular Formula: | C45H50ClN7O7S |
| SMILES: | CC1(C)CCC(CN2CCN(CC2)C2=CC=C(C(=O)NS(=O)(=O)C3=CC=C(NCC4CCOCC4)C(=C3)[N+]([O-])=O)C(OC3=CN=C4NC=CC4=C3)=C2)=C(C1)C1=CC=C(Cl)C=C1 |
| Structure: |
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| DrugBank Description: | Venetoclax is a BCL-2 inhibitor that was initially approved by the FDA in April 2016 . Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are important regulators of the apoptotic (programmed cell death) process , . Venetoclax is used to treat chronic lymphocytic leukemia (CLL) and certain types of small lymphocytic lymphoma . CLL is the most prevalent leukemia diagnosed in Western countries . Venetoclax was developed through reverse engineering of the BCL-2 protein family inhibitor, navitoclax . Venetoclax is approximately 10 times more potent than navitoclax with regard to induction of apoptosis in CLL cells . A new indication was approved in 2018 for the treatment patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy . Previously, this drug was indicated only for patients with 17p gene deletion . |
| CAS Number: | 1257044-40-8 |
| Molecular Weight: | 868.45 |
| DrugBank Indication: | A BCL-2 inhibitor indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy . |
| DrugBank Pharmacology: | Venetoclax induces rapid and potent onset apoptosis of CLL cells, powerful enough to act within 24h and to lead to tumor lysis syndrome , , . Selective targeting of BCL2 with venetoclax has demonstrated a manageable safety profile and has been shown to induce significant response in patients with relapsed CLL (chronic lymphocytic leukemia) or SLL (small lymphocytic leukemia), including patients with poor prognostic features . This drug is not expected to have a significant impact on the cardiac QT interval . Venetoclax has demonstrated efficacy in various types of lymphoid malignancies, including relapsed/ refractory CLL harboring deletion 17p, with an overall response rate of approximately 80% . |
| DrugBank MoA: | Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are necessary regulators of the apoptotic (anti-cell programmed death) process. This family comprises proapoptotic and prosurvival proteins for various cells. Cancer cells evade apoptosis by inhibiting programmed cell death (apoptosis). The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2-like 1 (BCL-X(L)), which has demonstrated clinical efficacy in some BCL-2-dependent hematological cancers . Selective inhibition of BCL-2 by venetoclax, sparing BCL-xL enables therapeutic induction of apoptosis without the negative effect of thrombocytopenia , . Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins, leading to mitochondrial outer membrane permeabilization and the activation of caspase enzymes. In nonclinical studies, venetoclax has shown cytotoxic activity in tumor cells that overexpress BCL-2 . |
| Targets: | Apoptosis regulator Bcl-2 antagonist&inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
