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

Bcl-2 Family

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

  • Bcl-xL

  • Bcl-W

  • Mcl-1

  • Bfl-1

  • Bcl-B

  • Bax

  • Bak

  • Bim

Cat. No. Product Name Effect Purity
  • HY-15531
    Venetoclax Inhibitor ≥98.0%
    Venetoclax (ABT-199; GDC-0199) is a highly potent, selective and orally bioavailable Bcl-2 inhibitor with a Ki of less than 0.01 nM. Venetoclax induces autophagy.
  • HY-10087
    Navitoclax Inhibitor ≥98.0%
    Navitoclax (ABT-263) is a potent and orally active Bcl-2 family protein inhibitor that binds to multiple anti-apoptotic Bcl-2 family proteins, such as Bcl-xL, Bcl-2 and Bcl-w, with a Ki of less than 1 nM.
  • HY-100741
    S63845 Inhibitor ≥98.0%
    S63845 is a potent and selective myeloid cell leukemia 1 (MCL1) inhibitor with a Kd of 0.19 nM for human MCL1.
  • HY-50907
    ABT-737 Inhibitor 99.59%
    ABT-737 is a selective and BH3 mimetic Bcl-2, Bcl-xL and Bcl-w inhibitor with EC50s of 30.3 nM, 78.7 nM, and 197.8 nM, respectively.
  • HY-19741
    A-1331852 Inhibitor 99.81%
    A-1331852 is an orally available BCL-XL selective inhibitor with a Ki of less than 10 pM.
  • HY-138697
    S65487 Inhibitor
    S65487 (VOB560) is a potent and selective Bcl-2 inhibitor. S65487 is also active on BCL-2 mutations, such as G101V and D103Y. S65487 has poor affinity with MCL-1, BFL-1 and BCL-XL. S65487 induces apoptosis and has anticaner activities.
  • HY-109184
    Murizatoclax Inhibitor
    Murizatoclax (AMG 397) is a potent, selective and orally active inhibitor of myeloid leukemia 1 (MCL-1) inhibitor, with a Ki of 15 pM. Murizatoclax competitive binds to the BH3-binding groove of MCL1 with pro-apoptotic BCL-2 family members. Murizatoclax can be used for the research of cancer.
  • HY-109185
    Pelcitoclax Inhibitor
    Pelcitoclax (APG-1252) is a potent Bcl-2/Bcl-xl inhibitor with antineoplastic and pro-apoptotic effects.
  • HY-101533
    AZD-5991 Inhibitor 99.50%
    AZD-5991 is a potent and selective Mcl-1 inhibitor with an IC50 of 0.7 nM in FRET assay and a Kd of 0.17 nM in surface plasmon resonance (SPR) assay.
  • HY-101565
    AMG-176 Inhibitor ≥99.0%
    AMG-176 is a potent, selective and orally active MCL-1 inhibitor, with a Ki of 0.13 nM.
  • HY-112218
    MIK665 Inhibitor ≥98.0%
    MIK665 (S-64315) is a special Mcl-1 inhibitor extracted from patent WO2016207225A1, compound Preparation 13, has an IC50 of 1.81 nM.
  • HY-19725
    A-1155463 Inhibitor 99.62%
    A-1155463 is a highly potent and selective BCL-XL inhibitor with an EC50 of 70 nM in Molt-4 cell.
  • HY-114855
    BT2 Inhibitor 99.56%
    BT2 is a BCKDC kinase (BDK) inhibitor with an IC50 of 3.19 μM. BT2 binding to BDK triggers helix movements in the N-terminal domain, resulting in the dissociation of BDK from the branched-chain α-ketoacid dehydrogenase complex (BCKDC). BT2 (compound 4) is also a potent and selective Mcl-1 inhibitor with a Ki value of 59 μM.
  • HY-10969
    Obatoclax Mesylate Inhibitor ≥98.0%
    Obatoclax Mesylate (GX15-070 Mesylate), a BH3 mimetic, is a pan-BCL-2 family proteins inhibitor with a Ki of 220 nM for BCL-2. Obatoclax Mesylate induces autophagy-dependent cell death and targets cyclin D1 for proteasomal degradation. Obatoclax Mesylate has anti-cancer and broad-spectrum antiparasitic activity.
  • HY-15607A
    WEHI-539 hydrochloride Inhibitor 98.16%
    WEHI-539 hydrochloride is a selective inhibitor of Bcl-XL with an IC50 of 1.1 nM.
  • HY-12048
    Chelerythrine chloride Inhibitor ≥98.0%
    Chelerythrine chloride is a potent, cell-permeable inhibitor of protein kinase C, with an IC50 of 660 nM. Chelerythrine chloride inhibits the Bcl-XL-Bak BH3 peptide binding with IC50 of 1.5 μM and displaces Bax from Bcl-XL. Chelerythrine chloride induces apoptosis and autophagy.
  • HY-P0081
    Bax inhibitor peptide V5 Inhibitor 99.62%
    Bax inhibitor peptide V5 (BIP-V5) is a Bax-mediated apoptosis inhibitor, used for cancer treatment.
  • HY-108705
    BI-3802 Inhibitor 99.68%
    BI-3802 is a highly potent BCL6 degrader and inhibits the Bric-à-brac (BTB) domain of BCL6 with an IC50 of ≤3 nM. BI-3802 induces the polymerization of BCL6 and promotes BCL6 degration depended on E3 ligase SIAH1. BI-3802 has antitumor activity.
  • HY-12468
    A-1210477 Inhibitor 98.89%
    A-1210477 is a potent and selective inhibitor of MCL-1 with a Ki of 0.45 nM. A-1210477 specifically binds MCL-1 and promotes apoptosis of cancer cells in an MCL-1-dependent manner.
  • HY-103269
    BAI1 Inhibitor 99.72%
    BAI1 is a selective and allosteric inhibitor of BAX, an apoptosis regulator. BAI1 directly binds to BAX and allosterically inhibits BAX activation. BAI1 has the potential for the research of diseases mediated by BAX-dependent cell death.

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.

Targets/MCE-Bcl-2-Family-Signaling-Pathway.png

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.

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