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-N0279
    Cardamonin
    		Inhibitor 98.38%
    Cardamonin can be found from cardamom, and can target various signaling molecules, transcriptional factors, cytokines and enzymes. Cardamonin can inhibit mTOR, NF-κB, Akt, STAT3, Wnt/β-catenin and COX-2. Cardamonin shows anticancer, anti-inflammatory, antimicrobial and antidiabetic activities.
    Cardamonin
  • HY-B0464
    Hydralazine hydrochloride
    		99.97%
    Hydralazine hydrochloride is an antihypertensive agent. Hydralazine hydrochloride can inhibit mitochondrial fission and human peritoneal mesothelial cell proliferation. Hydralazine hydrochloride has immunomodulation and anti-migratory effect. Hydralazine hydrochloride activates the intrinsic pathway of apoptosis and causes DNA damage.
    Hydralazine hydrochloride
  • HY-30219
    D-​(+)​-​Phenyllactic acid
    		Inhibitor 99.93%
    D-​(+)​-​Phenyllactic acid is an anti-bacterial agent, excreted by Geotrichum candidum, inhibits a range of Gram-positive from humans and foodstuffs and Gram-negative bacteria found in humans.
    D-​(+)​-​Phenyllactic acid
  • HY-B0257
    Levonorgestrel
    		Inhibitor 99.94%
    Levonorgestrel is an orally active inhibitor of progesterone (HY-N0437). Levonorgestrel has anticancer activity and can induce Apoptosis. Levonorgestrel can be used as a contraceptive and in combination with other medications. Levonorgestrel can be used in the study of osteoporosis and uterine leiomyoma.
    Levonorgestrel
  • HY-18705
    Azoramide
    		Inhibitor 99.57%
    Azoramide is a potent, orally active small-molecule modulator of the unfolded protein response (UPR). Azoramide improves ER protein folding and elevates ER chaperone capacity, which together protects cells against ER stress. Azoramide alleviates PLA2G6 mutant-induced ER stress through modulating unfolded protein response, and enhances the CERB signaling to rescue mitochondrial function, thereby preventing apoptosis of DA neurons. Azoramide has antidiabetic activity.
    Azoramide
  • HY-15607A
    WEHI-539 hydrochloride
    		Inhibitor 99.72%
    WEHI-539 hydrochloride is a selective inhibitor of Bcl-XL with an IC50 of 1.1 nM.
    WEHI-539 hydrochloride
  • HY-17510
    Gossypol (acetic acid)
    		Inhibitor 99.75%
    Gossypol acetic acid ((±)-Gossypol-acetic acid) binds to Bcl-xL protein and Bcl-2 protein with Kis of 0.5-0.6 μM and 0.2-0.3 mM, respectively.
    Gossypol (acetic acid)
  • HY-W250111
    Carboxymethyl chitosan
    		Activator
    Carboxymethyl chitosan is a derivative of chitosan. Carboxymethyl chitosan inhibits Apoptosis and ROS. Carboxymethyl chitosan increases the expression of Bcl-2 and reduces the expression of Bax, cytochrome c and caspase-3. Carboxymethyl chitosan inhibits the migration of various cells. Carboxymethyl chitosan exerts antitumor effects on Lewis tumors and hepatocarcinoma.
    Carboxymethyl chitosan
  • HY-12468
    A-1210477
    		Inhibitor 99.86%
    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.
    A-1210477
  • HY-B0402A
    Amantadine hydrochloride
    		Modulator ≥98.0%
    Amantadine (1-Adamantanamine) hydrochloride is an orally avtive and potent antiviral agent with activity against influenza A viruses. Amantadine hydrochloride inhibits several ion channels such as NMDA and M2, and also inhibits Coronavirus ion channels. Amantadine hydrochloride also has anti-orthopoxvirus and anticancer activity. Amantadine hydrochloride can be used for Parkinson's disease, postoperative cognitive dysfunction (POCD) and COVID-19 research.
    Amantadine hydrochloride
  • HY-129179
    Lisaftoclax
    		Inhibitor 99.28%
    Lisaftoclax (compound 6) is a dual Bcl-2 and Bcl-xl inhibitor with anti-tumor activity, extracted from patent WO2018027097A1. Lisaftoclax exhibits IC50 values of 2 nM and 5.9 nM for Bcl-2 and Bcl-xl, respectively.
    Lisaftoclax
  • HY-101972
    AZ-PFKFB3-67
    AZ-PFKFB3-67 is a potent and selective PFKFB3 kinase inhibitor with IC50s of 11, 159 and 1130 nM for PFKFB3, PFKFB2 and PFKFB1, respectively. AZ-PFKFB3-67 reduces MCL-1. AZ-PFKFB3-67 has neuroprotective activity.
    AZ-PFKFB3-67
  • HY-147081
    AS 1411
    		Inhibitor 99.52%
    AS 1411 (AGRO-100) is an oligonucleotide aptamer targeting nucleoproteins. AS 1411 inhibits tumor cell proliferation by affecting the activity of nucleoprotein-containing complexes and can be used as a carrier to precisely deliver nanoparticles, oligonucleotides and small molecules to cancer cells. AS 1411 reduces PRMT5 expression to inhibit tumor growth in DU145 prostate cancer cells. AS 1411 works by blocking the binding of nucleoproteins to bcl-2 mRNA in MCF-7 breast cancer cells. AS 1411-coupled Jin nanospheres can inhibit breast cancer cell proliferation in vitro and in mouse models, has the ability to cross the blood-brain barrier with low tissue toxicity.
    AS 1411
  • HY-120079
    MSN-125
    		Inhibitor 99.00%
    MSN-125 is a potent Bax and Bak oligomerization inhibitor. MSN-125 prevents mitochondrial outer membrane permeabilization (MOMP) with an IC50 of 4 μM. MSN-125 potently inhibits Bax/Bak-mediated apoptosis in HCT-116, BMK Cells, and primary cortical neurons, protects primary neurons against glutamate excitotoxicity.
    MSN-125
  • HY-109185
    Pelcitoclax
    		Inhibitor 99.70%
    Pelcitoclax (APG-1252) is a potent Bcl-2/Bcl-xl inhibitor with antineoplastic and pro-apoptotic effects.
    Pelcitoclax
  • HY-114118F
    Semaglutide, FITC labeled
    		99.83%
    Semaglutide, FITC labeled is a long-acting, selective, competitive, orally active GLP-1R agonist that can penetrate the blood-brain barrier. After activating GLP-1R, Semaglutide, FITC labeled promotes insulin secretion, inhibits gastric emptying and appetite, and at the same time enhances autophagy, inhibits oxidative stress and apoptosis. Semaglutide, FITC labeled also regulates mitochondrial function and lipid metabolism (such as reducing de novo lipogenesis in the liver). Semaglutide, FITC labeled has activities such as lowering blood sugar, reducing weight, neuroprotection (such as improving motor function in Parkinson's disease models, reducing α-synuclein aggregation) and improving hepatic steatosis. Semaglutide, FITC labeled can be used for the study of neurodegenerative diseases and liver diseases such as type 2 diabetes, obesity, Parkinson's disease, metabolic associated fatty liver disease (MASLD), and cancer.
    Semaglutide, FITC labeled
  • HY-B1971
    Deltamethrin
    		99.93%
    Deltamethrin (Decamethrin) is an orally active synthetic pyrethroid insecticide. Deltamethrin induces oxidative stress and results in inflammation and apoptosis via inhibiting Nrf2/HO-1 pathway. Deltamethrin has an anticancer effect by inducing apoptosis. Deltamethrin can be used extensively in pest control.
    Deltamethrin
  • HY-126741
    Azadirachtin
    		Inhibitor 99.06%
    Azadirachtin is an oral active triterpenoid compound with anticancer, antimalarial, anti-inflammatory, and insecticidal activities. Azadirachtin induces cell apoptosis through the mitochondrial pathway (by inhibiting Bcl-2/Bax ratio or activating Apaf-1 and caspase-3) or through death receptors (by inhibiting TNFR activation). Additionally, Azadirachtin exerts its anti-inflammatory effects by inhibiting NF-кB signaling pathway activation, and it exhibits insecticidal activity by inducing apoptosis in insect cells.
    Azadirachtin
  • HY-111381
    BI-3812
    		Inhibitor 99.26%
    BI-3812 is a highly efficient BCL6 inhibitor that is capable of suppressing the BTB domain of BCL6, with an IC50 value of ≤ 3 nM, exhibiting antitumor activity.
    BI-3812
  • HY-13560
    AVN-944
    		Modulator 99.89%
    AVN-944 (VX-944) is an orally active, potent, selective, noncompetitive and specific inhibitor of IMPDH (inosine monophosphate dehydrogenase). AVN-944 is an essential rate-limiting enzyme in de novo guanine nucleotide synthesis. AVN-944 is also an inhibitor of arenavirus RNA synthesis, and blocks arenavirus infection. AVN-944 has broad anti-cancer activities, and can be used for multiple myeloma (MM) and acute myeloid leukemia (AML) research.
    AVN-944
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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