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-N2897R
    Dihydrokaempferol (Standard)
    		Inhibitor
    Dihydrokaempferol (Standard) is the analytical standard of Dihydrokaempferol. This product is intended for research and analytical applications. Dihydrokaempferol is isolated from Bauhinia championii (Benth). Dihydrokaempferol induces apoptosis and inhibits Bcl-2 and Bcl-xL expression. Dihydrokaempferol is a good candidate for new antiarthritic agents.
    Dihydrokaempferol (Standard)
  • HY-W050044R
    L-Azetidine-2-carboxylic acid (Standard)
    		Activator
    L-Azetidine-2-carboxylic acid is a proline analog. L-Azetidine-2-carboxylic acid upregulates the lipid autophagy marker LC3-II via activation of the PERK pathway. L-Azetidine-2-carboxylic acid increases pro-apoptotic BAX protein. L-Azetidine-2-carboxylic acid induces ATF6 cleavage and upregulates phosphorylated eIF2α levels. L-Azetidine-2-carboxylic acid induces ER stress, inducing protein misfolding and aggregation. L-Azetidine-2-carboxylic acid shows teratogenic, pro-inflammatory and pro-apoptotic effects.
    L-Azetidine-2-carboxylic acid (Standard)
  • HY-115529
    (-)BI97D6
    (-)BI97D6 is a broad-spectrum inhibitor of the Bcl-2 protein family, inhibiting Mcl-1, Bcl-2, Bcl-xL and Bcl-1 with IC50 values ​​of 0.025, 0.031, 0.076 and 0.122 μM, respectively. (-)BI97D6 stimulates cell death through the Bak and Bax mediated mitochondrial apoptosis pathway. In addition, (-)BI97D6 inhibits Mcl-1 and can effectively induce apoptosis in acute myeloid leukemia (AML) cells.
    (-)BI97D6
  • HY-171031
    TFGF-18
    TFGF-18 is a GSK-3β inhibitor (IC50: 0.59 μM). TFGF-18 inhibits LPS-induced microglia activation and proinflammatory mediators release via inhibiting GSK-3β and downstream p65/NF-κB signaling. TFGF-18 inhibits neuronal apoptosis and oxidative stress, inhibits expressions of Bax, caspase3 and cleaved-caspase3 and increases the expression of Bcl-2. TFGF-18 has neuroprotection effect, inhibit neuroinflammation and attenuates cognitive impairment.
    TFGF-18
  • HY-182586
    Decyl gallate
    		Activator
    Decyl gallate is an antifungal (fungal) agent. Decyl gallate downregulates the expression of the pro-apoptotic (apoptosis) protein Bak, upregulates the expression of the anti-apoptotic protein Bcl-2, and inhibits DNA damage. Decyl gallate disrupts ALG12-mediated N-glycosylation, overactivates the UPR pathway, and simultaneously reduces fungal cell wall enzyme activity, chitin levels, mitochondrial activity, budding ability, cell viability, and host cell adhesion capacity. Decyl gallate reduces inflammatory responses induced by fungal infection and disrupts fungal membrane structure. Decyl gallate can be used in studies related to paracoccidioidomycosis and invasive fungal infections.
    Decyl gallate
  • HY-16232R
    Glufosfamide (Standard)
    		Inhibitor
    Glufosfamide (Standard) is the analytical standard of Glufosfamide. This product is intended for research and analytical applications. Glufosfamide is a glucose-conjugated alkylating cytotoxic agent and a derivative of Ifosfamide (HY-17419). Glufosfamide induces apoptosis frequency and increase the expression of caspase-9 and caspase-3 in cancer cells. Glufosfamide shows great anti-tumor activity in MiaPaCa-2-RFP mouse model. Glufosfamide can be used for the study of hepatocellular carcinoma, prostate cancer and pancreatic carcinoma.
    Glufosfamide (Standard)
  • HY-15613R
    Maritoclax (Standard)
    		Inhibitor
    Maritoclax (Standard) is the analytical standard of Maritoclax. This product is intended for research and analytical applications. Maritoclax (Marinopyrrole A) is a novel and specific Mcl-1 inhibitor with an IC50 value of 10.1 μM, and shows >8 fold selectivity than BCL-xl (IC50 > 80 μM).
    Maritoclax (Standard)
  • HY-N15466
    Longan cerebroside II
    Longan cerebroside II is a cerebroside found in Typhonium giganteum. Longan cerebroside II shows anti-apoptosis and neuroprotective activity. Longan cerebroside II reduces protein expression of caspase-9, caspase-3, and Bax, increases Bcl-2, cytochrome c levles.
    Longan cerebroside II
  • HY-102027R
    FX1 (Standard)
    		Inhibitor
    FX1 (Standard) is the analytical standard of FX1 (HY-102027). This product is intended for research and analytical applications. FX1 is a potent and specific BCL6 inhibitor, with an IC50 of around 35 μM.
    FX1 (Standard)
  • HY-165550
    Sphingosine
    		Inhibitor
    Sphingosine (C22-D-erythro-Sphingosine) is a metabolite of sphingolipid and a pro-Apoptotic signaling messenger. Sphingosine induces apoptosis via Caspase-dependent, mitochondria-dependent and lysosomal affinity detergent pathways, downregulates Bcl-2 and Bcl-xL, and truncates Bid and Bax. Sphingosine is used for cancer research.
    Sphingosine
  • HY-101083A
    (Rac)-BDA-366
    		Inhibitor
    (Rac)-BDA-366 (example 2) is the despinner of BDA-366 (HY-101083). BDA-366 is a potent Bcl-2 antagonist (Ki=3.3 nM), binding Bcl-2-BH4 domain with high affinity and selectivity. BDA-366 induces conformational change in Bcl-2 that abrogates its antiapoptotic function, converting it from a survival molecule to a cell death inducer. BDA-366 suppresses growth of lung cancer cells.
    (Rac)-BDA-366
  • HY-181030
    BDE30671203
    		Inhibitor
    BDE30671203 is a highly selective PLK1 inhibitor (IC50 = 2.163 nM). BDE30671203 induces G2/M phase arrest and Apoptosis. BDE30671203 downregulates key cell cycle regulators (CDC20, CDK1) and the anti-apoptotic gene Bcl-2. BDE30671203 exhibits anticancer activity against non-small cell lung cancer, large cell lung cancer, and liver cancer.
    BDE30671203
  • HY-N0475R
    Triptophenolide (Standard)
    		Activator
    Triptophenolide (Standard) (Hypolide) is the analytical standard of Triptophenolide (HY-N0475). This product is intended for research and analytical applications. Triptophenolide is a colorless crystal isolated from the ethyl acetate extract of Tripterygium wilfordii. Triptophenolide is an orally active pan‑antagonist of the androgen receptor (AR) with an IC50 of 467 nM against human wild‑type AR. Triptophenolide reduces AR expression, inhibits AR nuclear translocation, downregulates prostate‑specific antigen mRNA levels, and suppresses the growth of AR‑positive prostate cancer cells. Triptophenolide shows anti-tumor effects against breast cancer by inhibiting cell proliferation and migration, inducing G1-phase arrest and apoptosis, repressing xenograft tumor growth. Triptophenolide inhibits pyroptosis, alleviates tissue inflammation, and ameliorates synovial injury. Triptophenolide can be used for the study of prostate cancer, rheumatoid arthritis and breast cancer.
    Triptophenolide (Standard)
  • HY-12011A
    (Rac)-HA14-1
    		Inhibitor
    (Rac)-HA14-1 is the racemic form of HA14-1 (HY-12011). HA14-1 is a Bcl-2/Bcl-xL antagonist with an IC50 of approximately 9 μM against Bcl-2.
    (Rac)-HA14-1
  • HY-W747601
    Chlorphoxim
    		Activator
    Chlorphoxim is a broad-spectrum and highly efficient insecticide. Chlorphoxim kills pests by inhibiting AChE. Chlorphoxim inhibits the activities of SOD and CAT in zebrafish embryos. Chlorphoxim induces oxidative stress in zebrafish embryos by activating ROS. Chlorphoxim induces apoptosis by upregulating the expression levels of Bax, Bcl2 and p53 in zebrafish embryos. Chlorphoxim exhibits neurotoxicity and developmental toxicity. Chlorphoxim is used in agricultural research for the control of various pests.
    Chlorphoxim
  • HY-101778R
    ML311 (Standard)
    		Inhibitor
    ML311 (Standard) (EU-5346 (Standard)) is the analytical standard of ML311 (HY-101778). This product is intended for research and analytical applications. ML311 is a potent and selective inhibitor of the Mcl-1/Bim interaction.
    ML311 (Standard)
  • HY-119682
    Bax agonist 1
    Bax agonist 1 (compound SMBA2) is a Bax agonist (Ki=57.2 nM). Bax agonist 1 induces Bax conformational changes by blocking S184 phosphorylation, promoting Bax insertion into the mitochondrial membrane and forming Bax oligomers, which induce cytochrome c release and apoptosis in malignant cancer cells expressing Bax. Bax agonist 1 can be used in lung cancer research.
    Bax agonist 1
  • HY-W715812
    Bromuconazole
    		Inhibitor
    Bromuconazole is a triazole fungicide with oral efficacy and blood-brain barrier permeability. Bromuconazole protects crops from various fungal contaminations. Bromuconazole exhibits cytotoxicity against a variety of cancer cells, induces G0/G1 cell cycle arrest and inhibits DNA synthesis in cancer cells, and triggers cytoskeletal structural disorder, genotoxic damage, apoptotic (apoptosis) cell death, and mitochondrial membrane depolarization. Bromuconazole activates caspase-3, induces excessive production of ROS, p53 and Bax, lipid peroxidation, increased activities of SOD and CAT, and downregulates Bcl-2. By upregulating p-ERK1/2 and p-JNK, Bromuconazole disrupts the MAPK signaling pathway, impairs the cellular stress response of human trophoblast cells and endometrial cells, and damages the implantation process. Bromuconazole is applicable to research related to glioma, colon cancer, reproductive injury (implantation dysfunction), and cardiac dysfunction.
    Bromuconazole
  • HY-N1939R
    Icariside I (Standard)
    Icariside I (Standard) is the analytical standard of Icariside I (HY-N1939). This product is intended for research and analytical applications. Icariside I (GH01) is an orally active metabolite of icalin. Icariside I improves estrogen deficiency-induced osteoporosis by simultaneously regulating osteoblast and osteoclast differentiation. Icariside I promotes ATP (HY-B2176) or Nigericin (HY-127019)-induced mtROS production and NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity. Icariside I does not alter the activation of NLRC4 and AIM2 inflammasomes. Icariside I inhibits breast cancer proliferation, apoptosis, invasion, and metastasis by targeting the IL-6/STAT3 pathway. Icariside I is a kynurenine-AhR pathway inhibitor that alleviates cancer by blocking tumor immune escape.
    Icariside I (Standard)
  • HY-122481
    Thaspine acetate
    Thaspine acetate, an alkaloid, is a topoisomerase I and II inhibitor. Thaspine acetate induces cancer cell apoptosis. Thaspine acetate induces Bak and Bax activation, mitochondrial cytochrome c release and mitochondrial membrane permeabilization. Thaspine acetate can be isoalted from the cortex of the South American tree Croton lechleri.
    Thaspine acetate
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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