Bcl-2 remmers (Bcl-2 Inhibitors)

Overige Apoptosis Inhibitoren

Isoform-selectieve producten

• Aanbevolen remmers
• Remmers (41)
• Modulators (5)
• Chemische stof (1)
• Activators (7)
• Agonisten (5)

Cat.nr.	Productnaam	Informatie	Productgebruik Citaten	Productvalidaties
S8048	ABT-199 (Venetoclax)	Venetoclax (ABT-199, GDC-0199) is een Bcl-2-selectieve remmer met Ki van <0.01 nM in celvrije assays, >4800-voudig selectiever versus Bcl-xL en Bcl-w, en geen activiteit ten opzichte van Mcl-1. Van Venetoclax wordt gemeld dat het celgroeionderdrukking, apoptose, celcyclusarrest en autophagy induceert in triple-negatieve borstkanker MDA-MB-231-cellen. Fase 3.	Cell, 2025, S0092-8674(25)00689-0 Cell, 2025, S0092-8674(25)01233-4 Signal Transduct Target Ther, 2025, 10(1):161
S1001	Navitoclax (ABT-263)	Een krachtige remmer van Bcl-xL, Bcl-2 en Bcl-w met een Ki van ≤ 0,5 nM, ≤1 nM en ≤1 nM in celvrije assays, bindt Navitoclax (ABT-263) zwakker aan Mcl-1 en A1. Fase 2.	Cell, 2025, S0092-8674(25)00689-0 Nat Cancer, 2025, 6(2):259-277 Nat Metab, 2025, 7(12):2474-2488.
S8383	S63845	S63845 is een nieuwe, selectieve MCL-1-remmer met een Kd-waarde van 0,19 nM en heeft geen waarneembare binding met de andere BCL-2-leden, BCL-2 of BCL-XL.	Mol Cancer, 2025, 24(1):154 Nat Commun, 2025, 16(1):7853 Nat Commun, 2025, 16(1):4563
S1002	ABT-737	ABT-737 is een BH3-mimetische remmer van Bcl-xL, Bcl-2 en Bcl-w met een EC50 van respectievelijk 78,7 nM, 30,3 nM en 197,8 nM in celvrije assays; geen remming waargenomen tegen Mcl-1, Bcl-B of Bfl-1. ABT-737 induceert mitochondriale route Apoptosis en Mitophagy. Fase 2.	Signal Transduct Target Ther, 2025, 10(1):161 J Hepatol, 2025, S0168-8278(24)02830-7 Cell Rep Med, 2025, S2666-3791(25)00057-6
S7747	Ro-3306	RO-3306 is een ATP-competitieve en selectieve CDK1-remmer met een Ki van 20 nM, >15-voudige selectiviteit tegenover een divers panel van menselijke kinasen. RO-3306 verbetert p53-gemedieerde Bax-activering en mitochondriale apoptose.	Nat Commun, 2025, 16(1):6439 Nat Commun, 2025, 16(1):7898 Nucleic Acids Res, 2025, 53(21)gkaf1179
S1057	Obatoclax Mesylate (GX15-070)	Obatoclax Mesylate (GX15-070) is een antagonist van Bcl-2 met een Ki van 0,22 μM in een celvrije test, kan helpen bij het overwinnen van MCL-1 gemedieerde resistentie tegen Apoptosis.	Nat Commun, 2025, 16(1):2416 bioRxiv, 2024, 10.1101/2023.01.18.524628 Emerg Microbes Infect, 2022, 1-29
S7801	A-1331852	A-1331852 is een krachtige en selectieve BCL-XL-remmer met een Ki-waarde van minder dan 0,01 nM voor BCL-XL en respectievelijk 6 nM, 4 nM, 142 nM voor Bcl-2, Bcl-W, MCL-1. Het kan nuttig zijn bij de behandeling van kanker, immuun- en auto-immuunziekten.	Cell, 2025, S0092-8674(25)00689-0 Mol Cancer, 2025, 24(1):154 Haematologica, 2025, 110(1):78-91
S7790	A-1210477	A-1210477 is een potente en selectieve MCL-1 inhibitor met Ki en IC50 van respectievelijk 0,454 nM en 26,2 nM, >100-voudige selectiviteit over andere Bcl-2 familieleden.	Front Pharmacol, 2025, 16:1530270 Cell Rep, 2023, 42(10):113176 Int J Mol Sci, 2023, 24(13)11149
S1121	TW-37	TW-37 is een nieuwe niet-peptide-remmer van recombinant Bcl-2, Bcl-xL en Mcl-1 met een Ki van respectievelijk 0,29 μM, 1,11 μM en 0,26 μM in celvrije assays.	Signal Transduct Target Ther, 2025, 10(1):161 bioRxiv, 2024, 10.1101/2023.01.18.524628 Cells, 2023, 12(18)2247
S7800	A-1155463 Dihydrochloride	A-1155463 Dihydrochloride, een zeer krachtige en selectieve BCL-XL-remmer, vertoont picomolaire bindingsaffiniteit voor BCL-XL, en >1000-voudig zwakkere binding aan BCL-2 en verwante eiwitten BCL-W(Ki=19 nM) en MCL-1(Ki>440 nM).	Front Pharmacol, 2025, 16:1530270 iScience, 2024, 27(1):108503 World J Oncol, 2024, 15(3):472-481
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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]