xiap

MDM2/XIAP-IN-1 (compound 14) is an orally active dual inhibitor of MDM2 and XIAP, exhibiting anti-cancer activity with an IC50 of 0.3 μM and potential applications in cancer research [1].

XIAP/cIAP1 antagonist-1 is a potent, orally active XIAP/cIAP1 antagonist that acts on XIAP (EC50: 5.1 nM) and cIAP1 (EC50: 0.32 nM). xIAP/cIAP1 antagonist-1 dose-dependently inhibits tumour growth in vivo.

XIAP degrader-1 is a small primary amine molecule that promotes the degradation of X-linked apoptosis inhibitory protein (XIAP).

MDM2/XIAP-IN-3 (compound 3e), a dual inhibitor of MDM2/XIAP, diminishes MDM2 and XIAP protein levels while augmenting p53 expression, consequently suppressing cancer cell proliferation and inducing apoptosis [1].

MDM2/XIAP-IN-2 is a dual inhibitor targeting murine double minute 2 (MDM2) and X-linked inhibitor of apoptosis protein (XIAP). It promotes the degradation of MDM2 and impedes translation of XIAP mRNA, effectively inhibiting cancer cell proliferation. Notably, it exhibits potent activity against the acute lymphoblastic leukemia cell line EU-1, with an IC50 of 0.3 μM [1].

AZD5582 TFA is a potent IAP antagonist that binds to the BIR3 domain of cIAP1, cIAP2, and XIAP with IC50 values of 15, 21, and 15 nM, respectively.AZD5582 TFA induces apoptosis.

BV6 is an antagonist of c-IAP1 and XIAP, members of the inhibitors of apoptosis (IAP) family.

Birinapant (TL32711) is a synthetic small molecule that is both a peptidomimetic of second mitochondrial-derived activator of caspases (SMAC) and inhibitor of IAP (Inhibitor of Apoptosis Protein) family proteins, with potential antineoplastic activity.

SM-164 binds to XIAP protein containing both the BIR2 and BIR3 domains (IC50: 1.39 nM). It acts as an extremely potent antagonist of XIAP.

AZD5582 acetate is an inhibitor of IAPs, which binds to the BIR3 domains cIAP1, cIAP2, and XIAP with IC50s of 15, 21, and 15 nM, respectively. AZD5582 induces apoptosis.

LCL161, a SMAC mimetic, effectivity binds to and inhibits multiple IAPs (i.e. XIAP, c-IAP).

Neoandrographolide (Neoandrographiside) has potent hypolipidemic effect and protects the cardiovascular without significant liver damage.Neoandrographolide has anti-inflammatory effect, might result from inhibition of iNOS and COX-2 expression through inhibiting p38 MAPKs activation.Neoandrographolide as chemosensitizer in S-Jurkat and X chromosome-linked inhibitor of apoptosis protein (XIAP)-overexpressing Jurkat cells, a model for chemoresistance.

S-(N-Methylsulfinylbutylthiocarbamoyl)-L-cysteine (SFN-Cys) is an isothiocyanate derivative, functioning as an active metabolite of sulforaphane, a class I and II histone deacetylase (HDAC) inhibitor, and anticancer agent. This compound is generated from sulforaphane through intermediates - DL-sulforaphane glutathione and sulforaphane cysteinylglycine - via the mercapturic acid pathway enzymes. At a concentration of 20 µM, SFN-Cys diminishes invasion and migration of U87MG and U373 MG glioblastoma cells as observed in wound healing and chamber assays. Furthermore, at 45 µM, it significantly lowers the expression of α-tubulin, βIII-tubulin, stathmin 1, and X-linked inhibitor of apoptosis (XIAP), and also reduces cell density in paclitaxel-resistant A549 lung cancer cells (A549/T). Additionally, when used at 30 µM, SFN-Cys prompts apoptosis and cell cycle arrest at the G2/M phase in U87MG and U373 MG cells.

SNIPER(BRD)-1 is a chemical compound composed of a derivative of the IAP antagonist LCL-161 and the BET inhibitor (+)-JQ-1, linked together. It promotes the degradation of BRD4 through the ubiquitin-proteasome pathway and effectively degrades cIAP1, cIAP2, and XIAP with IC50 values of 6.8 nM, 17 nM, and 49nM, respectively[1].

SNIPER(ER)-87 is a chemical compound composed of a derivative of the inhibitor of apoptosis protein (IAP) ligand LCL161 conjugated to the estrogen receptor α (ERα) ligand 4-hydroxytamoxifen using a PEG linker. It effectively degrades the ERα protein with an IC50 value of 0.097 μM. Within cells, SNIPER(ER)-87 selectively recruits XIAP to ERα, and XIAP functions as the primary E3 ubiquitin ligase responsible for the degradation of ERα induced by SNIPER(ER)-87[1][2].

SM-164 Hydrochloride is a cell-permeable Smac mimetic compound. SM-164 binds to XIAP protein containing both the BIR2 and BIR3 domains(IC50 value of 1.39 nM) and functions as an extremely potent antagonist of XIAP.

MRK003 is a γ-secretase inhibitor exhibits promising in vitro pre-clinical activity in multiple myeloma and non-Hodgkin's lymphoma. MRK003 treatment induced caspase-dependent apoptosis and inhibited proliferation of MM and NHL cell lines and patient cells. Examination of signaling events after treatment showed time-dependent decrease in levels of the notch intracellular domain, Hes1 and c-Myc. MRK003 downregulated cyclin D1, Bcl-Xl and Xiap levels in NHL cells and p21, Bcl-2 and Bcl-Xl in MM cells. In addition, MRK003 caused an upregulation of pAkt, indicating crosstalk with the PI3K/Akt pathway.

GDC-0152 is a potent inhibitor of IAPs.

AZD5582 is an inhibitor of IAPs, which binds to the BIR3 domains cIAP1, cIAP2, and XIAP with IC50s of 15, 21, and 15 nM, respectively. It induces apoptosis.

AEG40730 is a potent and selective IAP antagonist and a BIR-binding tetrapeptide. AEG40730 binds to cIAP1 and cIAP2, facilitates their autoubiquitination and proteosomal degradation, and causes a dramatic reduction in RIP1 ubiquitination. Treatment with nanomolar concentrations of AEG40730 resulted in the loss of both XIAP and c-IAP1 proteins, albeit with different kinetics.

Alpinetin ((-)-alpinetin) has antibacterial activity.Alpinetin has anti-inflammatory activity.Alpinetin can enhance the sensitivity of HepG2 hepatoma cells to the chemotherapeutic agent CDDP. Alpinetin has strong anti-hepatoma and pancreatic cancer cells effects, by inhibiting proliferation , regulating of the Bcl-2 family and XIAP expression, releasing of cytochrome c and activating caspases.

IRES-C11 is a specific inhibitor of translation that targets the internal ribosome entry site (IRES) of the c-MYC gene. It functions by blocking the interaction between heterogeneous nuclear ribonucleoprotein A1, a trans-acting factor required for c-MYC IRES activity, and its corresponding IRES. Notably, IRES-C11 does not inhibit the IRES activity of BAG-1, XIAP, and p53.

SM-1295 serves as an antagonist to the inhibitor of apoptosis protein (IAP), demonstrating dissociation constant (Kd) values of 3077 nM for XIAP-BIR3, 3.2 nM for c-IAP1-BIR3, and 9.5 nM for c-IAP2-BIR3, respectively[1][2].

High affinity XIAP antagonist (Kd = 16 nM for the BIR3 domain of XIAP). Exhibits cytotoxicity in a wide range of cancer cell lines in vitro (EC50 = 13 nM in MDA-MB-231 cells). Also displays antitumor activity in a mouse breast cancer xenograft model. Enhances TRAIL-induced apoptosis in chronic lymphocytic leukemia (CLL) cells. Oost et al (2004) Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer. J.Med.Chem. 47 4417 PMID:15317454 |Loeder et al (2009) A novel paradigm to trigger apoptosis in chronic lymphocytic leukemia. Cancer Res. 69 8977 PMID:19920200

Phenoxodiol (Idronoxil) activates the mitochondrial caspase system, inhibits X-linked inhibitor of apoptosis(XIAP), disrupts FLICE inhibitory protein(FLIP) expression, and sensitizes the cancer cells to Fas-mediated apoptosis. Phenoxodiol induces cell cycle arrest in the G1/S phase of the cell cycle and upregulates p21WAF1 via a p53 independent manner. Phenoxodiol also inhibits DNA topoisomerase II.

SM-433 is a Smac mimetic and inhibitor of inhibitors of apoptosis (IAPs). SM-433 has a strong affinity for XIAP BIR3 protein (IC50 <1 μM).

TD1092, a pan-IAP degrader, effectively degrades cIAP1, cIAP2, and XIAP, catalyzing the activation of Caspase 3/7 and fostering apoptosis in cancer cells through IAP degradation. It also obstructs the TNFα-mediated NF-κB pathway, diminishing the phosphorylation of IKK, IkBα, p65, and p38, and operates as a PROTAC. This compound is utilized in cancer research [1].

Ibulocydine is a potent CDK inhibitor. Ibulocydine has high activity against Cdk7/cyclin H/Mat1 and Cdk9/cyclin T. Ibulocydine inhibited the growth of HCC cells more effectively than other Cdk inhibitors, including olomoucine and roscovitine, whereas ibulocydine as well as the other Cdk inhibitors and BMK-Y101 minimally influenced the growth of normal hepatocyte cells. Ibulocydine induced apoptosis in HCC cells, most likely by inhibiting Cdk7 and Cdk9. In vitro treatment of HCC cells with ibulocydine rapidly blocked phosphorylation of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II, a process mediated by Cdk7/9. Anti-apoptotic gene products such as Mcl-1, survivin, and X-linked IAP (XIAP) are crucial for the survival of many cell types, including HCC. Following the inhibition of RNA polymerase II phosphorylation, ibulocydine caused rapid down-regulation of Mcl-1, survivin, and XIAP, thus inducing apoptosis. Furthermore, ibulocydine effectively ind......

CT1-3 is a potent anti-cancer agent. CT1-3 regulates the JNK/Bcl-2/Bax/XIAP pathway, which induces mitochondria-mediated apoptosis. CT1-3 regulates the E-cadherin/Snail axis to inhibit epithelial mesenchymal transition (EMT) potentials in human cancer cells (HCCs) and suppresses tumourigenesis. CT1-3 has anti-tumour effects in mouse models and does not show significant hepatotoxicity or nephrotoxicity.

SW IV-52 is an XIAP-inhibitor that acts as a second mitochondria-derived activator of caspases (SMAC) mimetic.

Xevinapant (Debio-1143) is a potent Smac mimetic and an antagonist of IAP (inhibitor of apoptosis protein via E3 ubiquitin ligase), binding to XIAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 66.4 nM, 1.9 nM, and 5.1 nM, 50- to 100-fold higher affinities than the Smac AVPI peptide. Phase 1.

ASTX660 is an orally bioavailable dual antagonist of cIAP and XIAP.

MX106 is a survivin inhibitor which induces degradation of XIAP and/or cIAP1, and suppresses genotoxic NF-kappaB activation.

APG-1387 (SM-1387) is an IAP inhibitor that promotes the rapid degradation of cIAP1/2 and XIAP and exerts an anti-tumor effect on nasopharyngeal carcinoma stem cells. Studies have shown that APG-1387 combined with NPC's CDDP and 5-FU enhance chemoresensit

Anticancer agent 128 (compound 1) is an IAP inhibitor that covalently binds to the BIR3 domains of XIAP, cIAP1, and cIAP2, exhibiting IC50 values of 24.9 nM, 19.3 nM, and 10.3 nM, respectively [1].

TP-110 is a new proteasome inhibitor, which shows potent growth inhibition in various tumor cell lines. Treatment with TP-110 for 24 h in vitro induced apoptosis in multiple myeloma cell line RPMI8226. TP-110 reduced the intrinsic inhibitor of apoptosis proteins (IAPs), cIAP-1 and XIAP, that suppress executioner caspases.

MX107 is a survivin inhibitor which induces degradation of XIAP and/or cIAP1, and suppresses genotoxic NF-kappaB activation.

MX69 is the MDM2/XIAP inhibitor, blocking the MDM2 protein-XIAP RNA interaction, leading to MDM2 degradation.

SM-433 hydrochlorid is a Smac mimetic, an inhibitor of inhibitory apoptosis proteins (IAPs). SM-433 hydrochlorid is able to bind XIAP BIR3 protein with a potent IC50 <1 μM.

SBP-0636457 (SB1-0636457) is a SMAC mimetic and an inhibitor of inhibitor of apoptosis (IAP) proteins. It specifically binds to the BIR-domains of IAP proteins with a Ki value of 0.27 μM. SBP-0636457 holds potential for research in the fields of solid tumors and hematologic cancers.

Xevinapant hydrochloride (AT-406 HCl) , an orally active antagonist of multiple inhibitor of apoptosis proteins(IAP), inhibits progression of human ovarian Y binding to XIAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 66.4 nM, 1.9 nM, and 5.1 nM, 50- to 100-fold higher affinities than the Smac AVPI peptide.

Embelin (Embelic acid), isolated from the Japanese Ardisia herb, is an inhibitor of the X-linked inhibitor of apoptosis (IC50: 4.1 uM).

CST626 (Compound 9), a pan-IAP degrader PROTAC, effectively degrades XIAP, cIAP1, and cIAP2 in MM.1S cells with DC50 values of 0.7, 2.4, and 6.2 nM, respectively [1].

Anticancer agent 127 (142D6), an IAP inhibitor, covalently binds to the BIR3 domains of XIAP, cIAP1, and cIAP2, with IC50 values of 12 nM, 14 nM, and 9 nM, respectively, demonstrating anticancer effects [1].

AT-IAP is an effective dual antagonist of XIAP and cIAP1.

A-410099.1 is a novel potent xiap antagonist

Sanggenon G, a cell-permeable and potent inhibitor of X-linked inhibitor of apoptosis protein (XIAP), specifically binds to the XIAP BIR3 domain with a binding affinity of 34.26 μM, thereby enhancing caspase activation [1].

PROTAC pan-IAP degrader-1 (Compound 9) is a pan- IAP degrader PROTAC . PROTAC pan-IAP degrader-1 degrades XIAP , cIAP1 and cIAP2 with DC 50 s of 0.7, 2.4, and 6.2 nM in MM.1S cells, respectively [1] .

SM-164 Hydrochloride, a cell-permeable Smac mimetic compound, exhibits high affinity for the XIAP protein, specifically targeting both the BIR2 and BIR3 domains, with an IC50 value of 1.39 nM. This action categorizes it as an extremely potent XIAP antagonist.

T-3256336 is an orally available IAP antagonist agent that acts by selectively binding to and antagonizing protein interactions involving cellular IAP-1 (cIAP-1), cIAP-2, and X-linked IAP (XIAP).