XIAP
XIAP is a core inhibitor of apoptosis protein that directly restrains executioner caspase-3 and caspase-7 through BIR2-region mechanisms and inhibits initiator caspase-9 through BIR3 binding[1][2][3]. Mechanistically, its RING domain also supports E3 ubiquitin-ligase activity, linking XIAP biology to protein stability, apoptosis regulation, and non-apoptotic signaling contexts[4]. In innate immune signaling, XIAP ubiquitylates RIPK2 and recruits LUBAC after NOD2 stimulation, thereby enabling NF-κB activation and proinflammatory cytokine secretion[5]. In disease models and patient studies, XIAP deficiency associates with Crohn disease-like inflammatory bowel disease and defective NOD2 function in monocytes[6]. Compared with related cIAP1 and cIAP2 isoforms, XIAP has the clearest biochemical role as a direct caspase inhibitor, whereas cIAP1 and cIAP2 bind but do not efficiently inhibit caspases[7]. For experimental applications, selective XIAP antagonism can block NOD2-mediated inflammatory signaling by disrupting the XIAP-RIPK2 interaction, while broader IAP antagonists are used to test apoptosis sensitization mechanisms involving XIAP and cIAP proteins[8][9].- XIAP directly controls caspase-dependent apoptosis and connects apoptosis biology with inflammatory NOD2 signaling[1][5].- XIAP differs from cIAP1/cIAP2 because it directly inhibits caspase activity[7].- XIAP-RIPK2 antagonism provides a practical model for studying NOD2-driven inflammation[8].
References:
- [1]. Riedl SJ, et al. Structural basis for the inhibition of caspase-3 by XIAP. Cell. 2001 Mar 9;104(5):791-800. [Content Brief]
- [2]. Chai J, et al. Structural basis of caspase-7 inhibition by XIAP. Cell. 2001 Mar 9;104(5):769-80. [Content Brief]
- [3]. Shiozaki EN, et al. Mechanism of XIAP-mediated inhibition of caspase-9. Mol Cell. 2003 Feb;11(2):519-27. [Content Brief]
- [4]. Galbán S, et al. XIAP as a ubiquitin ligase in cellular signaling. Cell Death Differ. 2010 Jan;17(1):54-60. [Content Brief]
- [5]. Damgaard RB, et al. The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity. Mol Cell. 2012 Jun 29;46(6):746-58. [Content Brief]
- [6]. Aguilar C, et al. Characterization of Crohn disease in X-linked inhibitor of apoptosis-deficient male patients and female symptomatic carriers. J Allergy Clin Immunol. 2014 Nov;134(5):1131-41.e9. [Content Brief]
- [7]. Eckelman BP, et al. The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases. J Biol Chem. 2006 Feb 10;281(6):3254-60. [Content Brief]
- [8]. Goncharov T, et al. Disruption of XIAP-RIP2 Association Blocks NOD2-Mediated Inflammatory Signaling. Mol Cell. 2018 Feb 15;69(4):551-565.e7. [Content Brief]
- [9]. Ndubaku C, et al. Antagonism of c-IAP and XIAP proteins is required for efficient induction of cell death by small-molecule IAP antagonists. ACS Chem Biol. 2009 Jul 17;4(7):557-66. [Content Brief]
All Product Categories
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XIAP Related Products (31)
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Recombinant Proteins (3)
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Xevinapant
0 ImagesSynonyms: AT-406; Debio 1143; SM-406
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Embelin
0 ImagesEmbelin (Embelic acid), a potent, nonpeptidic XIAP inhibitor (IC50=4.1 μM), inhibits cell growth, induces apoptosis, and activates caspase-9 in prostate cancer cells with high levels of XIAP. Embelin blocks NF-kappaB signaling pathway leading to suppression of NF-kappaB-regulated antiapoptotic and metastatic gene products. Embelin also induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells.
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Jolkinolide B
0 ImagesJolkinolide B is a bioactive diterpene isolated from the roots of Euphorbia fischeriana Steud with oral activity. Jolkinolide B downregulates XIAP, cIAP1, cIAP2, and phosphorylated Akt, upregulates Smac, activates caspase-3 and caspase-9, and inhibits NF-κB, TGFβ/smad3 and JAK/STAT3 pathways. Jolkinolide B exerts comprehensive biological effects including inducing cancer cell apoptosis, suppressing inflammatory responses, improving lung function, alleviating hepatic steatosis and eliminating intracellular Mycobacterium tuberculosis. Jolkinolide B can be used for the research of leukemia, histiocytic lymphoma, asthma, metabolic dysfunction-associated steatotic liver disease and tuberculosis.
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Xevinapant hydrochloride
0 ImagesSynonyms: AT-406 hydrochloride; Debio 1143 hydrochloride; SM-406 hydrochlorideXevinapant (AT-406) hydrochloride is a potent and orally bioavailable Smac mimetic and an antagonist of the inhibitor of apoptosis proteins (IAPs). Xevinapant hydrochloride binds to XIAP, cIAP1, and cIAP2 proteins with Kis of 66.4, 1.9, and 5.1 nM, respectively. Xevinapant hydrochloride effectively antagonizes XIAP BIR3 protein in a cell-free functional assay, induces rapid degradation of cellular cIAP1 protein, and inhibits cancer cell growth in various human cancer cell lines. Xevinapant hydrochloride is highly effective in induction of apoptosis in xenograft tumors.
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HM90822
0 ImagesCat. No.: HY-12440CAS No.: 1363145-46-3HM90822 is an orally active IAP antagonist. HM90822 induces ubiquitination and proteasome-dependent degradation of XIAP, cIAP1 and cIAP2 in sensitive pancreatic cancer cells. HM90822 induces Apoptotic cell death. HM90822 inhibits tumor growth in Panc-1 pancreatic cancer xenograft and orthotopic mouse models. HM90822 can be used for the research of pancreatic cancer.
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Topo I/DDX5-IN-1
0 ImagesCat. No.: HY-181018CAS No.: 3040940-61-9Topo I/DDX5-IN-1 (Compound A10) is a Topo I and DDX5 inhibitor. Topo I/DDX5-IN-1 inhibits Topo I activity, binds to DDX5, and suppresses DDX5 function. Topo I/DDX5-IN-1 increases expression of γ-H2AX and p21, suppresses the expression of antiapoptotic proteins (Bcl-2 and XIAP), stimulates ROS generation, and triggers Apoptosis. Topo I/DDX5-IN-1 exhibits anticancer activity against pancreatic cancer, non-small cell lung cancer, skin cancer, and colorectal cancer.
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CSLP43
0 ImagesCat. No.: HY-123925CAS No.: 2244988-80-3CSLP43 is a selective RIPK2 and XIAP inhibitor with an IC50 of 19.9 nM against human RIPK2. CSLP43 binds to the ATP-binding pocket of RIPK2 and disrupts the interaction between RIPK2 and the BIR2 domain of XIAP or cIAP1. CSLP43 inhibits RIPK2 ubiquitination, NOD1-dependent inflammatory signaling pathways, NOD2-dependent inflammatory signaling pathways, as well as NF-κB activation associated with NOD agonists. CSLP43 is selective for the NOD1/NOD2 signaling pathway and does not inhibit the kinase activity of RIPK1 or RIPK3. CSLP43 is applicable to research related to Crohn's disease, Blau syndrome, early-onset sarcoidosis and early-onset inflammatory bowel disease.
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PBX-7016
0 ImagesCat. No.: HY-178226CAS No.: 3003834-34-9PBX-7016 is a Camptothecin (HY-16560) derivative. PBX-7016 can selectively inhibit Topoisomerase 1. PBX-7016 can specifically bind and degrade the cancer protein DDX5, thereby down-regulating the expression of anti-apoptotic proteins such as Survivin, Mcl-1, and XIAP, and promoting the apoptosis of cancer cells. PBX-7016 can be used to synthesis of ADCs.
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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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SBP-0636457
0 ImagesSynonyms: SBI-0636457; SB1-0636457
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Nurr1 agonist 14
0 ImagesCat. No.: HY-175352Purity: 99.42%Nurr1 agonist 14 (Compound 32) is a Nurr1 agonist with an EC50 of 0.09 μM for Nurr1. Nurr1 agonist 14 has significant neuroprotective activity with no influence of residual DHODH inhibition. Nurr1 agonist 14 upregulates neuroprotective genes including SOD2, SESN3, BIRC5, XIAP, FLRT2 and CRMP4 in dopaminergic neurons. Nurr1 agonist 14 can be used for neurodegenerative diseases such as Alzheimer′s disease (AD), Parkinson′s disease (PD) and multiple sclerosis (MS) research.
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CDK9-IN-45
0 ImagesCat. No.: HY-179023CDK9-IN-45 (Compound B11) is a highly selective CDK9 inhibitor with IC50 values for CDK9 and CDK1 of 7.13 and 489.5 nM respectively. CDK9-IN-45 exhibits a potent inhibitory effect on colorectal cancer cells. CDK9-IN-45 induces cell apoptosis and leads to significant accumulation of ROS. CDK9-IN-45 activates Caspase-3, downregulates Mcl-1, XIAP, and c-Myc. CDK9-IN-45 can be used for research on colorectal cancer.
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ZLMT-72
0 ImagesCat. No.: HY-179633ZLMT-72 is an orally active dual CDK2 and CDK9 inhibitor with IC50s of 0.741 nM and 1.03 nM, respectively. ZLMT-72 shows good selectivity in kinase profiling andcholinesterase inhibition activity. ZLMT-72 has strong antiproliferative effects in the colorectal cancer (CRC) cell line HCT116 (GI50 < 0.1 nM). ZLMT-72 induces apoptosis by inhibiting thephosphorylation of retinoblastoma and RNA polymerase II, resulting in downregulation of antiapoptotic proteins (Mcl-1 and XIAP). ZLMT-72 can be used for the study of colorectal cancer (CRC).
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TP-110
0 ImagesCat. No.: HY-118522CAS No.: 688737-95-3TP-110 is a proteasome inhibitor. TP-110 specifically inhibits the protease-like activity of the 20S proteasome, but does not affect the trypsin-like or peptidyl-glutamyl peptide hydrolysis activity. TP-110 inhibits the NF-κB pathway, activates caspase-8, -9, and -3, and causes PARP cleavage, significantly reducing the levels of cIAP-1 and XIAP. TP-110 causes cell cycle arrest at the G2/M phase and promotes apoptosis of cancer cells. TP-110 can be used in cancer research of prostate cancer and multiple myeloma, etc.
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Topoisomerase I inhibitor 17
0 ImagesCat. No.: HY-168739CAS No.: 2413582-45-1Topoisomerase I inhibitor 17 (Compound 7h) is a Topoisomerase I (Top1) inhibitor. Topoisomerase I inhibitor 17 reduces DDX5 and reverses the locking of Top1 activity by DDX5. Topoisomerase I inhibitor 17 induces Top1-mediated DNA damage and promotes reactive oxygen species (ROS) production. Topoisomerase I inhibitor 17 induces Apoptosis (reduces antiapoptotic proteins XIAP, Bcl-2, Survivin and up-regulates pro-apoptotic proteins Bax, γH2AX). Topoisomerase I inhibitor 17 also blocks the progression of the G2/M checkpoint and induces cell cycle arrest. Topoisomerase I inhibitor 17 significantly inhibits colony formation and cell migration in colorectal cancer cells. Topoisomerase I inhibitor 17 effectively reduces tumors in human PDX tumor mice.
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