Bcl-2 (B-cell lymphoma 2) is the founding pro-survival member of the Bcl-2 protein family, exerting its pro-survival function in response to a broad range of apoptotic stimuli through the inhibition of the mitochondrial outer membrane permeabilization (MOMP) process and the release of mitochondrial cytochrome c. [show the full text]
Bcl-2 Inhibidores (Bcl-2 Inhibitors)
Otro Apoptosis Inhibidores
- Inhibidores destacados
- Inhibidores (41)
- Moduladores (5)
- Producto químico (1)
- Activadores (7)
- Agonistas (5)
| Nº Cat. | Nombre del producto | Información | Citas de uso del producto | Validaciones del producto |
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| S8048 | ABT-199 (Venetoclax) | Venetoclax (ABT-199, GDC-0199) es un inhibidor selectivo de Bcl-2 con un Ki de <0,01 nM en ensayos sin células, >4800 veces más selectivo frente a Bcl-xL y Bcl-w, y sin actividad sobre Mcl-1. Se ha informado que Venetoclax induce la supresión del crecimiento celular, la apoptosis, la detención del ciclo celular y la autofagia en células MDA-MB-231 de cáncer de mama triple negativo. Fase 3. |
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| S1001 | Navitoclax (ABT-263) | Un potente inhibidor de Bcl-xL, Bcl-2 y Bcl-w con Ki de ", "0,5 nM, ", "1 nM y ", "1 nM en ensayos sin células, Navitoclax (ABT-263) se une más débilmente a Mcl-1 y A1. Fase 2. |
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| S8383 | S63845 | S63845 es un nuevo inhibidor selectivo de MCL-1 con un valor de Kd de 0,19 nM y no presenta unión discernible a otros miembros de Bcl-2, Bcl-2 o BCL-XL. |
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| S1002 | ABT-737 | ABT-737 es un inhibidor mimético de BH3 de Bcl-xL, Bcl-2 y Bcl-w con EC50 de 78.7 nM, 30.3 nM y 197.8 nM en ensayos sin células, respectivamente; no se observó inhibición contra Mcl-1, Bcl-B o Bfl-1. ABT-737 induce la Apoptosis por la vía mitocondrial y la Mitophagy. Fase 2. |
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| S7747 | Ro-3306 | RO-3306 es un inhibidor de CDK1 ATP-competitivo y selectivo con un Ki de 20 nM, con una selectividad >15 veces mayor frente a un panel diverso de quinasas humanas. RO-3306 mejora la activación de Bax mediada por p53 y la apoptosis mitocondrial. |
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| S1057 | Obatoclax Mesylate (GX15-070) | Obatoclax Mesylate (GX15-070) es un antagonista de Bcl-2 con un Ki de 0,22 μM en un ensayo sin células, que puede ayudar a superar la resistencia a la apoptosis mediada por MCL-1. |
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| S7801 | A-1331852 | A-1331852 es un potente y selectivo inhibidor de BCL-XL con un valor de Ki inferior a 0,01 nM para BCL-XL y de 6 nM, 4 nM, 142 nM para Bcl-2, Bcl-W, MCL-1 respectivamente. Puede ser útil en el tratamiento del cáncer, enfermedades inmunitarias y autoinmunes. |
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| S7790 | A-1210477 | A-1210477 es un inhibidor potente y selectivo de MCL-1 con una Ki y IC50 de 0,454 nM y 26,2 nM, respectivamente, con una selectividad >100 veces superior sobre otros miembros de la familia Bcl-2. |
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| S1121 | TW-37 | TW-37 es un nuevo inhibidor no peptídico de Bcl-2, Bcl-xL y Mcl-1 recombinantes con Ki de 0,29 μM, 1,11 μM y 0,26 μM en ensayos libres de células, respectivamente. |
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| S7800 | A-1155463 Dihydrochloride | A-1155463 Dihydrochloride, un inhibidor BCL-XL altamente potente y selectivo, muestra una afinidad de unión picomolar a BCL-XL, y una unión >1000 veces más débil a BCL-2 y proteínas relacionadas BCL-W (Ki=19 nM) y MCL-1 (Ki>440 nM). |
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Bcl-2 (B-cell lymphoma 2) is encoded by the Bcl-2 gene and is the first identified member of a large family of apoptosis regulatory proteins (Bcl-2 family) that derives its name from the B-cell lymphoma 2, as it is the second member of a variety of proteins initially described in the t(14;18) chromosomal translocation in human follicular B-cell lymphomas. Bcl-2 contains four Bcl-2 homology domains (BH1-BH4) that mediate the formation of homodimer and heterodimer with relative proteins such as Bax, Bad, Bak and Bcl-xL, and a trans-membrane (TM) domain that mediates insertion into the outer membrane of the mitochondria and the endoplasmic reticulum. Bcl-2 proteins are generally integrated within the outer mitochondrial membrane (OMM), and may also be in the cytosol or ER membrane. The Bcl-2 and other antiapoptotic members of the Bcl-2 family preserve the outer mitochondrial membrane (OMM) integrity, thus inhibiting the mitochondrial signaling pathway of apoptosis, by complex interactions with the proapoptotic Bcl-2 proteins such as Bax, Bak, Bim, Puma and tBid. [1][2]
Bcl-2 suppresses apoptosis in response to a broad range of stress stimuli, including those frequently encountered during tumor development, such as oncogene activation, DNA damage, hypoxia (oxygen deprivation), loss of appropriate growth signals and anoikis (loss of cell attachment). In healthy cells, Bax and Bak are kept in check by the pro-survival Bcl-2 family members and the binding of BH3-only proteins unleashes Bax/Bak. Bcl-2 is also critical for the survival of renal epithelial stem cells during embryogenesis, melanocyte progenitors and mature B and T lymphocytes. Bcl-2 over-expression accelerates Eu-myc-induced lymphomagenesis, but loss of endogenous Bcl-2 does not prevent or delay Eu-myc-induced B lymphoma development. Bcl-2 proteins also constitutively binds to Beclin-1, and its dissociation through post-translational modification of Beclin-1 and/or Bcl-2 proteins such as phosphorylation by JNK1, or direct competition for the Bcl-2 BC groove by another BH3-only protein such as Bad, may be sufficient to induce autophagy, leading to the suggestion that autophagy and apoptosis are mechanistically linked. Single-site phosphorylation at Serine 70 (S70) is required for the antiapoptotic function of Bcl-2, and multisite phosphorylation at Threonine 69, S70, and S87 has been reported to inactivate Bcl-2. Phosphorylation of Bcl-2 has been shown to enhance activity to allow response to extracellular growth-factor-mediated signals. [1][2][3]
In addition, Bcl-2 is over-expressed in human follicular centre B-cell lymphoma; high levels of Bcl-2 are also detected in significant numbers of chronic lymphocytic leukaemia (CLL), DLBCL and mantle cell lymphoma, as well as in certain solid tumours(brain, breast and lung). The upregulation of Bcl-2 in CLL and other cancers has been attributed to the hypo-methylation of the Bcl-2 promoter or, possibly more importantly due to hemizygous or homozygous loss of the micro RNAs (miRs) 15a and 16-1 that negatively regulate Bcl-2. The dysregulated Bcl-2 proteins in cancer can lead to increased survival of abnormal cells, which are thought to be involved in resistance to conventional cancer treatment. Mice that constitutively express both Myc and Bcl-2 transgenes develop lymphoblastic leukaemia with high incidence, while shut-down of the inducible Bcl-2 transgene in lymphoma-burdened bi-transgenic mice results in tumor regression and significantly prolonged animal survival in many cases, indicating that inactivation of Bcl-2 constitutes a promising new approach to cancer therapy. Small molecule mimetics of BH3-only proteins that can directly target pro-survival Bcl-2 family members are being developed as a novel therapeutic approach. ABT-737 and the closely related orally bioavailable ABT-263, belong to the BH3 mimetic small molecule inhibitors, targeting Bcl-2 and Bcl-2-related proteins such as Bcl-xL and Bcl-w, therefore promoting tumor regression in murine xeno-transplanation models of certain human lymphomas or small cell lung carcinomas and in primary patient-derived follicular lymphoma cells. [1][4]
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