PANoptosis
PANoptosis
PANoptosis is a novel pathway of inflammatory programmed cell death (PCD) that integrates key molecular components and phenotypic features from three major pathways-pyroptosis, apoptosis, and necroptosis-and is specifically regulated by the PANoptosome complex. PANoptosis involves extensive crosstalk and cannot be blocked by inhibiting any single pathway alone. PANoptosis exerts host-protective effects in anti-infective and anti-tumor contexts, while mediating pathological damage in cases of excessive inflammation, cytokine storms, and organ injury.
The PANoptosome complex responds to stimuli such as infection and cellular stress; it is organized into three functional layers-sensor, adaptor, and effector proteins-and, upon activation, simultaneously triggers membrane rupture, the release of cellular contents, and the secretion of inflammatory cytokines. Currently, four distinct subtypes of the PANoptosome complex have been identified: ZBP1 (which recognizes Z-RNA), AIM2 (which recognizes dsDNA), RIPK1 (which responds to intracellular bacterial infections), and NLRP12 (which responds to hemolytic events). All four subtypes are dependent on transcriptional regulation by IRF1 and are negatively regulated by factors such as ADAR1. The core components of the four PANoptosis subtypes are as follows[1]:
1. ZBP1-PANoptosome contains: ZBP1 (sensor), NLRP3, ASC, caspase-1/6/8, RIPK1/3.
2. AIM2-PANoptosome contains: AIM2 (sensor), Pyrin, ZBP1, ASC, caspase-1/8, RIPK1.
3. FADD-RIPK1-PANoptosome contains: RIPK1 (sensor), RIPK3, NLRP3, ASC, and Caspase-1/8.
4. NLRP12-PANoptosome contains: NLRP12 (sensor), ASC, Caspase-8, and RIPK3.
The PANoptosome complex responds to stimuli such as infection and cellular stress; it is organized into three functional layers-sensor, adaptor, and effector proteins-and, upon activation, simultaneously triggers membrane rupture, the release of cellular contents, and the secretion of inflammatory cytokines. Currently, four distinct subtypes of the PANoptosome complex have been identified: ZBP1 (which recognizes Z-RNA), AIM2 (which recognizes dsDNA), RIPK1 (which responds to intracellular bacterial infections), and NLRP12 (which responds to hemolytic events). All four subtypes are dependent on transcriptional regulation by IRF1 and are negatively regulated by factors such as ADAR1. The core components of the four PANoptosis subtypes are as follows[1]:
1. ZBP1-PANoptosome contains: ZBP1 (sensor), NLRP3, ASC, caspase-1/6/8, RIPK1/3.
2. AIM2-PANoptosome contains: AIM2 (sensor), Pyrin, ZBP1, ASC, caspase-1/8, RIPK1.
3. FADD-RIPK1-PANoptosome contains: RIPK1 (sensor), RIPK3, NLRP3, ASC, and Caspase-1/8.
4. NLRP12-PANoptosome contains: NLRP12 (sensor), ASC, Caspase-8, and RIPK3.
References:
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PANoptosis Related Products (12)
Related Products (12)
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Melatonin
0 ImagesMelatonin is a hormone made by the pineal gland that can activate melatonin receptor and inhibit PANoptosis. Melatonin plays a role in sleep and possesses important antioxidative and anti-inflammatory properties. Melatonin is a novel selective ATF-6 inhibitor and induces human hepatoma cell apoptosis through COX-2 downregulation. Melatonin attenuates palmitic acid-induced (HY-N0830) mouse granulosa cells apoptosis via endoplasmic reticulum stress.
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Cucurbitacin E
0 ImagesSynonyms: α-Elaterin; α-ElaterineCucurbitacin E is a CDK1 inhibitor that significantly inhibits the activity of the cyclin B1/CDC2 complex. Cucurbitacin E also induces PANoptosis in adrenocortical carcinoma cells in a ZBP1-dependent manner. Cucurbitacin E exhibits synergistic effects with Mitotane (HY-13690); when used in combination, they effectively eliminate tumors.
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MNS
0 ImagesMNS (NSC 170724), the beta-nitrostyrene derivative, is an orally active tyrosine kinase inhibitor, a broad-spectrum antiplatelet agent, and a PANoptosis inhibitor. MNS inhibits Src, Syk, and FAK with IC50 of 27.3, 2.8, and 97.6 μM, respectively. MNS inhibits NLRP3 inflammasome and β1 integrin. MNS completely inhibits U46619, ADP-, arachidonic acid-, collagen-, and thrombin-induced platelet aggregation with IC50 values of 2.1, 4.1, 5.8, 7.0, and 12.7 μM, respectively. MNS is cytotoxic to a variety of cells.
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TD1092
0 ImagesTD1092 is a pan-IAP degrader, degrades cIAP1, cIAP2, and XIAP. TD1092 activates Caspase 3/7, and promotes cancer cells apoptosis via IAP degradation. TD1092 inhibits TNFα mediated NF-κB pathway and reduces the phosphorylation of IKK, IkBα, p65, and p38. TD1092 can act as PROTAC, and is used for cancer research.
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Photosensitizer-9
0 ImagesCat. No.: HY-182066Photosensitizer-9 is an iridium (III)-based photosensitizer with anti-melanoma activity. Photosensitizer-9 exhibits significant phototoxicity (IC50=0.98 μM) and an ideal phototoxicity index (PI=3.05). Under light irradiation, Photosensitizer-9 generates large amounts of intracellular •OH in an oxygen-independent manner. Photosensitizer-9 mediates photodynamic therapy under hypoxic conditions and synergistically activates PANoptosis (by upregulating cleaved Caspase-3, GSDMD-N, p-MLKL), ferroptosis (by disrupting the GSH-GPX4-LPO axis), apoptosis, pyroptosis and necroptosis in melanoma cells. Photosensitizer-9 induces immunogenic cell death by promoting the release of damage-associated molecular patterns under hypoxic conditions and increases the maturation rate of dendritic cells. Photosensitizer-9 reduces tumor volume in melanoma-bearing mice. Photosensitizer-9 is applicable to relevant studies on melanoma.
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Selinexor (Standard)
0 ImagesSynonyms: KPT-330 (Standard)
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PARP1/EZH2-IN-1
0 ImagesCat. No.: HY-179386PARP1/EZH2-IN-1 is a selective PARP1 and EZH2 dual inhibitor. PARP1/EZH2-IN-1 has IC50s of 28 nM, 414 nM and 74 nM for PARP1, PARP2 and EZH2, respectively. PARP1/EZH2-IN-1 inhibits the proliferation and migration of TNBC cells (triple-negative breast Cancer cells). PARP1/EZH2-IN-1 induces PANoptosis (Apoptosis, Pyroptosis and Necroptosis), increases the level of reactive oxygen species (ROS), and activates related inflammatory pathways. PARP1/EZH2-IN-1 can be used in triple-negative breast cancer research.
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TNI-97
0 ImagesCat. No.: HY-175030CAS No.: 2790425-52-2TNI-97 is a selective and orally active HDAC6 inhibitor, with an IC50 of 0.2 nM. TNI-97 potently inhibited TNBC cell MDA-MB-453 growth and clonogenicity. TNI-97 induces PANoptosis including apoptosis, necroptosis and pyroptosis in MDA-MB-453 cells. TNI-97 shows antitumor activity in the mice carrying the MDA-MB-453 xenograft or carrying murine-derived TNBC cell allografts. TNI-97 can be used for the study of triple-negative breast cancer.
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K103
0 ImagesCat. No.: HY-117087CAS No.: 1071544-43-8K103 is an inhibitor discovered from the screen that is an analog of the serotonin antagonist benzazocine. K103 exhibited inhibition of SHIP homologues, labelling it a pan-SHIP1/2 inhibitor, but the molecule had no effect on another 5' inositol phosphatase, OCRL. In line with the "two PIPs hypothesis", the molecule exhibited significant anti-tumour effects against a variety of cell lines, particularly breast cancer cells. Additional studies with K103 revealed that inhibition of SHIP1/2 in multiple myeloma cells resulted in G2/M cell cycle arrest followed by extensive apoptosis via activation of the caspase cascade. K103 fits the commonly used small molecule agent property profile, but while this work was being conducted, it was discovered that K103 caused psychoactive effects in mice, which limited the utility of the molecule in vivo. Therefore, certain synthetic studies were conducted on this tryptamine to identify the features that needed to be present in the molecule to maintain pan-SHIP1/2 inhibition in order to design an inhibitor with favourable pharmacodynamic properties and an improved side effect profile.
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Cucurbitacin E (Standard)
0 ImagesCat. No.: HY-N0417RCAS No.: 18444-66-1Synonyms: α-Elaterin (Standard); α-Elaterine (Standard)Cucurbitacin E (Standard) is the analytical standard of Cucurbitacin E. This product is intended for research and analytical applications. Cucurbitacin E is a natural compound which from Cucurbitaceae plants. Cucurbitacin E significantly suppresses the activity of the cyclin B1/CDC2 complex.
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Apoptosis inducer 36
0 ImagesCat. No.: HY-168927CAS No.: 2831492-41-0Apoptosis inducer 36 (Compound 42) exhibits anti-leukemic activity through reduction of leukemia stem cells (LSCs) and induction of differentiation. Apoptosis inducer 36 inhibits the proliferation of AML cells, arrests cell cycle at G1 phase, and induces PANoptosis including apoptosis, pyroptosis and necrosis. Prodrug of apoptosis inducer 36 exhibits orally active antitumor efficacy in mouse model.
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