2. Signaling Pathways
  3. Apoptosis
  4. Bcl-2 Family

Bcl-2 Family

Bcl-2 Family

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Bcl-2 is a family of evolutionarily related proteins. These proteins govern mitochondrial outer membrane permeabilization (MOMP) and can be either pro-apoptotic (Bax, Bad, Bak and Bok among others) or anti-apoptotic (including Bcl-2 proper, Bcl-xL, and Bcl-w, among an assortment of others). There are a total of 25 genes in the Bcl-2 family known to date. Human genes encoding proteins that belong to this family include: Bak1, Bax, Bal-2, Bok, Mcl-1.

Bcl-2 Family Isoform Specific Products:

Bcl-2 Family Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-N2693
    6,8-Diprenylorobol
    		Modulator
    6,8-Diprenylorobol, a prenylated isoflavone, is a nature product that could be isolated from the leaves of Cudrania tricuspidata. 6,8-Diprenylorobol antiproliferative effect and induces apoptosis through activation of p53 and generation of ROS.
    6,8-Diprenylorobol
  • HY-RS01421
    BCL2L1 Human Pre-designed siRNA Set A
    		Inhibitor

    BCL2L1 Human Pre-designed siRNA Set A contains three designed siRNAs for BCL2L1 gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.
    BCL2L1 Human Pre-designed siRNA Set A
  • HY-16669
    Mcl1-IN-1
    		Inhibitor 98.02%
    Mcl1-IN-1 is an inhibitor of myeloid cell factor 1 (Mcl-1) (IC50=2.4 µM).
    Mcl1-IN-1
  • HY-152169
    BIHC
    		Inhibitor ≥98.0%
    BIHC is a TNF blocker with anti-inflammatory activity. BIHC can significantly inhibit the proliferation of hepatocellular carcinoma (HCC) cells and exhibits potent cytotoxicity against the HepG2 cell line, capable of inducing cell apoptosis , while demonstrating relatively low toxicity towards normal hepatocytes. Additionally, BIHC can be used for research on inflammatory bowel disease (IBD).
    BIHC
  • HY-B0621R
    Triclabendazole (Standard)
    Triclabendazole (Standard) is the analytical standard of Triclabendazole. This product is intended for research and analytical applications. Triclabendazole is an orally active parasite inhibitor. Triclabendazole has anti-Leishmania activity and induces gasdermin E (GSDME)-dependent pyroptosis by caspase-3 activation. Triclabendazole can be used for the research of fasciola hepatica.
    Triclabendazole (Standard)
  • HY-N1414A
    3′,6-Disinapoylsucrose
    		Inhibitor
    3′,6-Disinapoylsucrose is a type of oligosaccharide that's effective when taken orally, and it has antidepressant, anti-anxiety, and antioxidant properties. 3′,6-Disinapoylsucrose inhibits neuronal apoptosis by lowering the ratio of Bax to Bcl-2 in hippocampal neurons, and it enhances cognitive function in APP/PS1 transgenic mice by activating the CREB/BDNF signaling pathway.
    3′,6-Disinapoylsucrose
  • HY-15607
    WEHI-539
    		Inhibitor
    WEHI-539 is a selective inhibitor of Bcl-XL with an IC50 of 1.1 nM.
    WEHI-539
  • HY-161242A
    CBI1 formic
    		Inhibitor
    CBI1 formic is a covalent BAX inhibitor. CBI1 formic selectively derivatizes BAX at C126 and inhibits BAX activation by triggering ligands or point mutagenesis. CBI1 formic blocks t-2-hex lipidation and oligomerization of BAX. CBI1 formic inhibits BAX activation induced by BH3 ligands, F116A mutagenesis or t-2-hex.
    CBI1 formic
  • HY-112218A
    (R)-MIK665
    		Inhibitor
    (R)-MIK665 is the less active enantiomer of MIK665. MIK665 is a special Mcl-1 inhibitor with an IC50 of 1.81 nM.
    (R)-MIK665
  • HY-138697A
    S65487 sulfate
    		Inhibitor 98.08%
    S65487 (VOB560) sulfate, a potent and selective Bcl-2 inhibitor, is a proagent of S55746. S65487 sulfate is also active on BCL-2 mutations, such as G101V and D103Y. S65487 sulfate has poor affinity with MCL-1, BFL-1 and BCL-XL. S65487 sulfate induces apoptosis and has anticaner activities.
    S65487 sulfate
  • HY-N0168AS
    (Rac)-Hesperetin-d3
    (Rac)-Hesperetin-d3 is the deuterium labeled (Rac)-Hesperetin. (Rac)-Hesperetin is the racemate of Hesperetin. Hesperetin is a natural flavanone, and acts as a potent and broad-spectrum inhibitor against human UGT activity. Hesperetin induces apoptosis via p38 MAPK activation.
    (Rac)-Hesperetin-d<sub>3</sub>
  • HY-128607
    Mcl1-IN-9
    		Inhibitor
    Mcl1-IN-9 is a potent myeloid cell leukemia-1 (Mcl-1) Inhibitor with an IC50 of 446 nM in reengineered BCR-ABL+ B-ALL cells and a Ki of 0.03 nM.
    Mcl1-IN-9
  • HY-155188
    NWP-0476
    		Inhibitor
    NWP-0476 is BCL-2/BCL-xL inhibitor. NWP-0476 has a modified structure with fine-tuned BCL-xL activity. NWP-0476 can be used for relapsed T-acute lymphoblastic leukemia (T-ALL) research.
    NWP-0476
  • HY-100866
    F1324
    		Inhibitor
    F1324 is a potent, high affinity peptidic inhibitor of B cell lymphoma 6 (BCL6) with an IC50 of 1 nM. F1324 exhibits binding t1/2 value of 441 s and has strong inhibition activity against BCL6 PPI.
    F1324
  • HY-131247
    Bcl-2-IN-2
    		Inhibitor
    Bcl-2-IN-2 is a potent and selective Bcl-2 inhibitor with an IC50 of 0.034 nM and also inhibits Bcl-xL with an IC50 of 43 nM, showing >1000-fold selectivity for Bcl-2 over Bcl-xL.
    Bcl-2-IN-2
  • HY-111537
    rel-AZ5576
    		Inhibitor
    rel-AZ5576 is a selective CDK9 inhibitor with the activity of downregulating Mcl-1 and MYC mRNA transcription and protein expression in diffuse large B-cell lymphoma by inhibiting CDK9, promoting MYC protein turnover, reducing MYC phosphorylation on the stable Ser62 residue and downregulating MYC transcriptional targets, inhibiting the growth of diffuse large B-cell lymphoma cell lines in vitro and in vivo and independent of the cell origin.
    rel-AZ5576
  • HY-156620
    Lacutoclax
    		Inhibitor
    Lacutoclax is a Bcl-2 inhibitor with antineoplastic activity.
    Lacutoclax
  • HY-118874
    Oblimersen
    		Inhibitor
    Oblimersen is a BCL-2 inhibitor targeting BCL-2 RNA. Oblimersen specifically binds to the first six codons of the bcl-2 mRNA sequence, resulting in degradation of bcl-2 mRNA and induces apoptosis by down-regulating expression of Bcl-2. Oblimersen can be used for cancer research.
    Oblimersen
  • HY-101533A
    AZD-5991 Racemate
    		Inhibitor
    AZD-5991 Racemate is the racemate of AZD-5991. AZD-5991 Racemate is a Mcl-1 inhibitor with an IC50 of <3 nM in FRET assay.
    AZD-5991 Racemate
  • HY-130261
    Mcl-1 antagonist 1
    		Antagonist
    Mcl-1 antagonist 1 is a Mcl-1 protein antagonist extracted from patent WO2019173181, compound 200.
    Mcl-1 antagonist 1
Cat. No. Product Name / Synonyms Application Reactivity
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Download Bcl-2 Family Signaling Pathway Map.

Bcl-2 family members have been grouped into three classes. The anti-apoptotic subfamily contains the Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B proteins, which suppress apoptosis and contain all four Bcl-2 homology domains, designated BH1-4. The pro-apoptotic subfamily contain BH1-3 domains, such as Bax, Bak, and Bok. A third class of BH3 only proteins Bad, Bid, Bim, Noxa and Puma have a conserved BH3 domain that can bind and regulate the anti-apoptotic BCL-2 proteins to promote apoptosis [1].


The intrinsic pathway is initiated by various signals, principally extracellular stimuli. BH3-only proteins (Bim, Bid, Bad, Noxa, Puma) engage with anti-apoptotic Bcl-2 family proteins to relieve their inhibition of Bax and Bak to activate them. Next, Bax and Bak are oligomerized and activated, leading to mitochondrial outer membrane permeabilization. Once mitochondrial membranes are permeabilized, cytochrome c and/or Smac/DIABLO is released into the cytoplasm, wherein they combine with an adaptor molecule, Apaf-1, and an inactive initiator Caspase, Pro-caspase 9, within a multiprotein complex called the apoptosome. Smac/DIABLO inhibits IAPs to activate Caspase 9. Caspase 9 activates Caspase 3, which is the initiation step for the cascade of Caspase activation. The extrinsic pathway can be activated by cell surface receptors, such as Fas and TNF Receptor, subsequently activating Caspase 8, and leads to Caspase 3 activation and cell demolition. Caspases in turn cleave a series of substrates, activate DNases and orchestrate the demolition of the cell. Bcl-2 family proteins are also found on the endoplasmic reticulum and the perinuclear membrane in hematopoietic cells, but they are predominantly localized to mitochondria [2]. 

 

Reference:
[1]. Cotter TG, et al. Apoptosis and cancer: the genesis of a research field. Nat Rev Cancer. 2009 Jul;9(7):501-7.

[2]. Kang MH, et al. Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res. 2009 Feb 15;15(4):1126-32.

Bcl-2 Family Isoform Comparison

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