Research graph
References from “SMAC”-Down for the Apoptosis-Restoring Drug, Xevinapant: What Does Its Story Reveal?. Local targets link to admitted publications; unresolved targets remain external evidence.
Apoptotic cell death in disease—current understanding of the NCCD 2023
10.1038/s41418-023-01153-w · 2023 · External reference
Targeting apoptosis in cancer therapy
10.1038/s41571-020-0341-y · 2020 · External reference
Therapeutic development and current uses of BCL-2 inhibition
10.1182/hematology.2020000154 · 2020 · External reference
Tetravalent death receptor 5 (DR5) agonist ozekibart (INBRX-109) + FOLFIRI in 2L+ colorectal adenocarcinoma (CRC): preliminary results from a phase 1 study
10.1200/jco.2025.43.4_suppl.129 · 2025 · External reference
The TRAIL apoptotic pathway in cancer onset, progression and therapy
10.1038/nrc2465 · 2008 · External reference
X-linked IAP is a direct inhibitor of cell-death proteases
10.1038/40901 · 1997 · External reference
Prevention of apoptosis by a baculovirus gene during infection of insect cells
10.1126/science.1962198 · 1991 · External reference
LCL161, a SMAC-mimetic, preferentially radiosensitizes human papillomavirus-negative head and neck squamous cell carcinoma
10.1158/1535-7163.mct-18-1157 · 2019 · External reference
Prognostic value of XIAP level in patients with various cancers: a systematic review and meta-analysis
10.7150/jca.28229 · 2019 · External reference
Immunohistochemical detection of X-linked inhibitor of apoptosis in head and neck squamous cell carcinoma
10.1016/j.anndiagpath.2006.12.012 · 2007 · External reference
Targeting IAP proteins for therapeutic intervention in cancer
10.1038/nrd3627 · 2012 · External reference
Nuclear expression of cIAP-1, an apoptosis inhibiting protein, predicts lymph node metastasis and poor patient prognosis in head and neck squamous cell carcinomas
10.1016/j.canlet.2004.11.049 · 2005 · External reference
Overexpression of cIAP2 contributes to 5-FU resistance and a poor prognosis in oral squamous cell carcinoma
10.1038/bjc.2011.387 · 2011 · External reference
Apoptosis-associated release of Smac/DIABLO from mitochondria requires active caspases and is blocked by Bcl-2
10.1093/emboj/20.23.6627 · 2001 · External reference
Smac mimetics induce inflammation and necrotic tumour cell death by modulating macrophage activity
10.1038/cddis.2013.449 · 2013 · External reference
Modulation of immune signalling by inhibitors of apoptosis
10.1016/j.it.2012.06.004 · 2012 · External reference
Inhibitor of apoptosis proteins (IAPs) and their antagonists regulate spontaneous and tumor necrosis factor (TNF)-induced proinflammatory cytokine and chemokine production
10.1074/jbc.m112.422410 · 2013 · External reference
The opposing roles of cellular inhibitor of apoptosis proteins in cancer
10.5402/2012/928120 · 2012 · External reference
Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs)
10.1007/s10495-017-1375-1 · 2017 · External reference
IAP antagonists induce anti-tumor immunity in multiple myeloma
10.1038/nm.4229 · 2016 · External reference
IAP antagonists enhance cytokine production from mouse and human iNKT cells
10.1158/2326-6066.cir-17-0490 · 2018 · External reference
A phase I study of the SMAC-mimetic birinapant in adults with refractory solid tumors or lymphoma
10.1158/1535-7163.mct-15-0475 · 2015 · External reference
DEBIO 1143, an IAP inhibitor, reverses carboplatin resistance in ovarian cancer cells and triggers apoptotic or necroptotic cell death
10.1038/s41598-018-35860-z · 2018 · External reference
A potent and orally active antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in clinical development for cancer treatment
10.1021/jm101505d · 2011 · External reference
Evasion of apoptosis and treatment resistance in squamous cell carcinoma of the head and neck
10.1016/j.ctrv.2024.102773 · 2024 · External reference
FDA grants breakthrough therapy designation for debiopharm’s novel chemo-radio sensitizer Debio 1143 for front-line treatment of head & neck cancer
External reference
Merck provides update on xevinapant program in locally advanced head and neck cancer
2024 · External reference
The radiosensitizing activity of the SMAC-mimetic, Debio 1143, is TNFα-mediated in head and neck squamous cell carcinoma
10.1016/j.radonc.2015.05.017 · 2015 · External reference
Initial testing (stage 1) of LCL161, a SMAC mimetic, by the pediatric preclinical testing program
10.1002/pbc.23167 · 2012 · External reference
Abstract 2752: effects of Debio 1143, a novel oral IAP inhibitor, in monotherapy and in combination with platinum drugs in human SCCHN tumor specimens
10.1158/1538-7445.am2014-2752 · 2014 · External reference
Abstract 2055: the SMAC-mimetic Debio 1143 efficiently enhanced chemo and radiotherapy in head and neck squamous cell carcinoma models
10.1158/1538-7445.am2013-2055 · 2013 · External reference
Radiosensitization of head and neck squamous cell carcinoma by a SMAC-mimetic compound, SM-164, requires activation of caspases
10.1158/1535-7163.mct-10-0643 · 2011 · External reference
SMAC mimetic Debio 1143 and ablative radiation therapy synergize to enhance antitumor immunity against lung cancer
10.1158/1078-0432.ccr-17-3852 · 2019 · External reference
The effect of xevinapant combined with ionizing radiation on HNSCC and normal tissue cells and the impact of xevinapant on its targeted proteins cIAP1 and XIAP
10.3390/cells12121653 · 2023 · External reference
XIAP is a predictor of cisplatin-based chemotherapy response and prognosis for patients with advanced head and neck cancer
10.1371/journal.pone.0031601 · 2012 · External reference
Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: results of a first-in-man study
10.1007/s00280-015-2709-8 · 2015 · External reference
Phase I trial of Debio 1143, an antagonist of inhibitor of apoptosis proteins, combined with cisplatin chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck
10.1158/1078-0432.ccr-20-0425 · 2020 · External reference
Exploratory window-of-opportunity trial to investigate the tumor pharmacokinetics/pharmacodynamics of the IAP antagonist Debio 1143 in patients with head and neck cancer
10.1111/cts.13002 · 2022 · External reference
Synergistic effects of Smac mimetic APG-1387 with anti-PD-1 antibody are attributed to increased CD3 + NK1.1 + cell recruitment secondary to induction of cytokines from tumor cells
10.1186/s12935-024-03373-7 · 2024 · External reference
Xevinapant plus avelumab in advanced solid tumours, with a dose expansion in advanced non-small-cell lung cancer: exploratory biomarker, safety and efficacy analyses from an open-label, nonrandomised phase Ib study
10.1177/17588359251332154 · 2025 · External reference
Xevinapant combined with pembrolizumab in patients with advanced, pretreated, colorectal and pancreatic cancer: results of the phase Ib/II CATRIPCA trial
10.1158/1078-0432.ccr-23-2893 · 2024 · External reference
589 Xevinapant plus nivolumab in patients with advanced solid tumors who progressed on prior anti–PD-1/PD-L1 treatment: results of a dose-optimization, exploratory phase 1b/2 trial
10.1136/jitc-2022-sitc2022.0589 · 2022 · External reference
Debio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 study
10.1016/s1470-2045(20)30327-2 · 2020 · External reference
Extended follow-up of a phase 2 trial of xevinapant plus chemoradiotherapy in high-risk locally advanced squamous cell carcinoma of the head and neck: a randomised clinical trial
10.1016/j.ejca.2022.12.015 · 2023 · External reference
Abstract 3443: the IAP antagonist xevinapant, in combination with high-dose cisplatin chemoradiotherapy, induces NF-kB and apoptotic pathway biomarkers in patients with high-risk locally advanced squamous cell carcinoma of the head and neck
10.1158/1538-7445.am2022-3443 · 2022 · External reference
Leveraging the mechanism of action (MOA) of xevinapant, an IAP inhibitor, for phase 3 dosing (RP3D) strategies in combination with radiation (RT) and chemoradiotherapy (CRT) in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN)
10.1200/jco.2023.41.16_suppl.e18001 · 2023 · External reference
TrilynX: a phase 3 trial of xevinapant and concurrent chemoradiation for locally advanced head and neck cancer
10.1200/jco.2021.39.15_suppl.tps6091 · 2021 · External reference
Xevinapant or placebo plus chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck: TrilynX phase III study design
10.2217/fon-2021-1634 · 2022 · External reference
Xevinapant plus radiotherapy in resected, high-risk, cisplatin-ineligible LA SCCHN: the phase III XRay Vision study design
10.2217/fon-2023-0774 · 2024 · External reference
A double-blind, randomized, phase III study of radiotherapy combined with cetuximab + xevinapant compared to radiotherapy combined with cetuximab (standard of care) + placebo in patients with LA SCCHN, unfit for high-dose cisplatin [clinical trial registration] [Internet]
2025 · External reference
Merck provides update on phase III TrilynX study in locally advanced head and neck cancer [Internet]
2024 · External reference
Xevinapant or placebo plus platinum-based chemoradiotherapy in unresected locally advanced squamous cell carcinoma of the head and neck (TrilynX): a randomized, phase III study
10.1200/jco-25-00272 · 2025 · External reference
A randomized, double-blind placebo-controlled, phase 3 study of Debio 1143 in combination with platinum-based chemotherapy and standard fractionation intensity-modulated radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck, suitable for definitive chemoradiotherapy (TrilynX) [Clinical trial registration] [Internet]
2025 · External reference
SMAC mimetics inhibit human T cell proliferation and fail to augment type 1 cytokine responses
10.1016/j.cellimm.2023.104674 · 2023 · External reference
Xevinapant plus chemoradiotherapy negatively sculpts the tumor-immune microenvironment in head and neck cancer
10.1158/2767-9764.crc-25-0604 · 2025 · External reference
Letter to the Editor: SMAC mimetics inhibit human T cell proliferation and fail to augment type 1 cytokine responses
10.1016/j.cellimm.2023.104772 · 2024 · External reference
Prognostic factors in head and neck cancer: a 10-year retrospective analysis in a single-institution in Italy
10.14639/0392-100x-1246 · 2017 · External reference
Censored patients in Kaplan–Meier plots of cancer drugs: an empirical analysis of data sharing
10.1016/j.ejca.2020.09.031 · 2020 · External reference
An imbalance in competing mortality favouring Debio 1143
10.1016/s1470-2045(20)30614-8 · 2020 · External reference
Guidance on interim analysis methods in clinical trials
10.1017/cts.2023.552 · 2023 · External reference
Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial
10.1016/s1470-2045(24)00100-1 · 2024 · External reference
Unresolved reference
2021 · External reference
Concept paper on the revision of the guideline on the evaluation of anticancer medicinal products and appendices [Internet]
2025 · External reference
Apoptosis and acute kidney injury
10.1038/ki.2011.120 · 2011 · External reference
Expression of Smac/Diablo in tubular epithelial cells and during acute renal failure
10.1046/j.1523-1755.64.s86.10.x · 2003 · External reference
Second mitochondrial activator of caspases mimetics accelerate progression of locally advanced head and neck cancer
10.1200/jco-25-01024 · 2025 · External reference
Model-informed selection of the recommended phase III dose of the inhibitor of apoptosis protein inhibitor, xevinapant, in combination with cisplatin and concurrent radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck
10.1002/cpt.3065 · 2024 · External reference
IAP antagonist GDC-0917 is more potent than Debio1143 in promoting cell death, c-IAP1 degradation and tumor growth inhibition
10.1038/s41419-022-05283-w · 2022 · External reference
Small molecule inhibitors targeting the “undruggable” survivin: the past, present, and future from a medicinal chemist’s perspective
10.1021/acs.jmedchem.3c01130 · 2023 · External reference
Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy
10.1038/s41392-022-01046-3 · 2022 · External reference
Hepatitis B virus and inhibitor of apoptosis proteins – a vulnerable liaison
10.1038/cddiscovery.2016.14 · 2016 · External reference
SMAC mimetics induce autophagy-dependent apoptosis of HIV-1-infected macrophages
10.1038/s41419-020-02761-x · 2020 · External reference
An orally-available monovalent SMAC mimetic compound as a broad-spectrum antiviral
10.1093/procel/pwad033 · 2024 · External reference
