Target Information
| Target General Information | Top | |||||
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| Target ID |
T56510
(Former ID: TTDC00168)
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| Target Name |
Apoptosis regulator Bcl-xL (BCL-xL)
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| Synonyms |
Bcl2like protein 1; Bcl2L1; Bcl2-L-1; Bcl-XL; Bcl-2-like protein 1; BCLX; BCL2L; Apoptosis regulator Bcl-X
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| Gene Name |
BCL2L1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Myeloproliferative neoplasm [ICD-11: 2A20] | |||||
| Function |
Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis. Potent inhibitor of cell death.
Click to Show/Hide
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| BioChemical Class |
B-cell lymphoma Bcl-2
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| UniProt ID | ||||||
| Sequence |
MSQSNRELVVDFLSYKLSQKGYSWSQFSDVEENRTEAPEGTESEMETPSAINGNPSWHLA
DSPAVNGATGHSSSLDAREVIPMAAVKQALREAGDEFELRYRRAFSDLTSQLHITPGTAY QSFEQVVNELFRDGVNWGRIVAFFSFGGALCVESVDKEMQVLVSRIAAWMATYLNDHLEP WIQENGGWDTFVELYGNNAAAESRKGQERFNRWFLTGMTVAGVVLLGSLFSRK Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T74I49 | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
| 1 | ABT-263 | Drug Info | Phase 3 | Myelofibrosis | [2] | |
| 2 | Obatoclax | Drug Info | Phase 2 | Solid tumour/cancer | [1] | |
| 3 | APG-1252 | Drug Info | Phase 1/2 | Small-cell lung cancer | [3] | |
| 4 | AZD0466 | Drug Info | Phase 1/2 | Hematologic tumour | [4] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 14 Inhibitor drugs | + | ||||
| 1 | ABT-263 | Drug Info | [5], [6], [7] | |||
| 2 | Obatoclax | Drug Info | [1] | |||
| 3 | APG-1252 | Drug Info | [8] | |||
| 4 | AZD0466 | Drug Info | [9] | |||
| 5 | Indole-based analog 2 | Drug Info | [10] | |||
| 6 | Indole-based analog 3 | Drug Info | [10] | |||
| 7 | PMID27744724-Compound-10 | Drug Info | [10] | |||
| 8 | PMID27744724-Compound-18 | Drug Info | [10] | |||
| 9 | PMID27744724-Compound-21 | Drug Info | [10] | |||
| 10 | PMID27744724-Compound-26 | Drug Info | [10] | |||
| 11 | PMID27744724-Compound-27 | Drug Info | [10] | |||
| 12 | 4'-FLUORO-1,1'-BIPHENYL-4-CARBOXYLIC ACID | Drug Info | [11] | |||
| 13 | EAPB0203 | Drug Info | [13] | |||
| 14 | WEHI-0103122 | Drug Info | [12] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | E-003 | Drug Info | [12] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Phase II study of obatoclax mesylate (GX15-070), a small-molecule BCL-2 family antagonist, for patients with myelofibrosis. Clin Lymphoma Myeloma Leuk. 2010 Aug;10(4):285-9. | |||||
| REF 2 | ClinicalTrials.gov (NCT04472598) Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis (TRANSFORM-1). U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT04210037) Study of APG-1252 Plus Paclitaxel in Patients With Relapsed/Refractory Small Cell Lung Cancer. U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT04865419) Study of AZD0466 Monotherapy or in Combination in Patients With Advanced Haematological Malignancies. U.S. National Institutes of Health. | |||||
| REF 5 | Clinical pipeline report, company report or official report of Roche (2009). | |||||
| REF 6 | ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo. Mol Cancer Ther. 2008 Oct;7(10):3265-74. | |||||
| REF 7 | ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008 May 1;68(9):3421-8. | |||||
| REF 8 | Bcl-2/Bcl-xl inhibitor APG-1252-M1 is a promising therapeutic strategy for gastric carcinoma. Cancer Med. 2020 Jun;9(12):4197-4206. | |||||
| REF 9 | Design and optimisation of dendrimer-conjugated Bcl-2/x L inhibitor, AZD0466, with improved therapeutic index for cancer therapy. Commun Biol. 2021 Jan 25;4(1):112. | |||||
| REF 10 | Mcl-1 inhibitors: a patent review.Expert Opin Ther Pat. 2017 Feb;27(2):163-178. | |||||
| REF 11 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 12 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2845). | |||||
| REF 13 | EAPB0203, a member of the imidazoquinoxaline family, inhibits growth and induces caspase-dependent apoptosis in T-cell lymphomas and HTLV-I-associated adult T-cell leukemia/lymphoma. Blood. 2008 Apr 1;111(7):3770-7. | |||||
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