Ask about this productRelated genes to: XPO1 antibody
- Gene:
- XPO1 NIH gene
- Name:
- exportin 1
- Previous symbol:
- -
- Synonyms:
- CRM1, CRM-1, emb
- Chromosome:
- 2p15
- Locus Type:
- gene with protein product
- Date approved:
- 1998-05-12
- Date modifiied:
- 2019-03-12
Related products to: XPO1 antibody
Related articles to: XPO1 antibody
- Exportin 1 (XPO1/CRM1) is a clinically validated anticancer target whose inhibition blocks nuclear export and promotes cancer cell apoptosis. Current XPO1 inhibitors rely on covalent Michael addition to Cys528 in the nuclear export signal binding groove of XPO1. Here, we describe a novel XPO1 inhibitor, FR-027, that targets Cys528 through nucleophilic aromatic substitution. In contrast to clinical-stage XPO1 inhibitors selinexor and eltanexor, FR-027 acts reversibly and does not promote XPO1 protein degradation. Structural analysis of the XPO1-FR-027 complex reveals covalent modification of Cys528 and a closed-groove conformation that prevents degradation. FR-027 demonstrates potent on-target activity across multiple cancer cell types and delays disease progression while extending overall survival in xenograft and syngeneic models, including intracranial tumors. Notably, FR-027 does not induce significant thrombocytopenia, lymphopenia, or neutropenia in heavily treated mice. These findings underscore the distinct molecular and pharmacological properties of FR-027 and support its further evaluation for clinical development in diseases with significant unmet medical needs. - Source: PubMed
Publication date: 2026/07/22
Van Hauwenhuyse JanneReniers FelienPersoons LeentjeNoppen SamWing Casey ENiesman Ashley BFung Ho Yee JoyceVanstreels ElsJacquemyn MaartenBoel ElineVankerckhoven AnnBerckmans YaniKwanten BertCoosemans AnVan den Mooter GuyChook Yuh MinDehaen WimDaelemans Dirk - Nucleocytoplasmic transport (NCT) regulates the spatial distribution of proteins and RNA between the nucleus and cytoplasm. NCT dysregulation can mislocalize tumor suppressors, DNA-repair factors, transcription factors, and drug targets in cancer. In this review, we conceptualize NCT-dependent protein mislocalization as a spatial regulatory framework for anticancer drug resistance, rather than as a catalogue of transport components. We systematically discuss how nuclear pore complex (NPC) remodeling, transport-receptor imbalance, post-translational modification (PTM)-regulated cargo routing, signaling-NCT crosstalk, nuclear localization signal/nuclear export signal (NLS/NES) alterations, and tumor microenvironmental pressures jointly drive aberrant nucleocytoplasmic distribution. These processes can further regulate apoptosis, DNA-damage repair, oncogenic transcription, oxidative stress adaptation and drug-target accessibility, which ultimately promote drug tolerance and therapeutic resistance. We further distinguish clinically validated mechanisms from preclinical phenotypes and correlative observations. At present, the most advanced therapeutic evidence mainly supports exportin 1/chromosome region maintenance 1 (XPO1/CRM1) inhibition, particularly selinexor in selected hematologic malignancies; in contrast, strategies targeting the NPC, importins, PTM pathways, microenvironmental cues, or localization signals remain largely investigational. By integrating mechanistic, preclinical, translational, and clinical evidence, this review aims to synthesize current evidence on NCT-dependent protein mislocalization as a resistance-relevant axis and to highlight the need for cargo-specific biomarkers and rational combination strategies to translate this biology into anticancer therapy. - Source: PubMed
Publication date: 2026/08/13
Zhu XuepingHe MisiWang LingSu RuiZhong LinGuo TingWang HaixiaZou Dongling - KRAS G12C-mutant advanced non-small cell lung cancer (NSCLC) is currently treated with KRAS G12C covalent inhibitors, such as sotorasib, or RAS (ON) G12-selective inhibitors; however, response rates and progression-free survival remain limited, with recurrence occurring in most patients. Although mechanisms of resistance in KRAS G12C cell lines are multifarious, they have been attributed to EGFR activation and Aurora kinase A (AURKA) signaling via Ras-related nuclear protein (Ran). Ran-GTP cooperates with Exportin-1 (XPO1), which has been identified as essential in KRAS-mutant NSCLC cells. - Source: PubMed
Publication date: 2026/08/17
González JèssicaCai XuetingDiao WenjingRoué GaëlValència-Clua KevinOlmo-González DanielGonzález-Cao MaríaJain AnishaJantus-Lewintre EloisaGiménez-Capitán AnaMolina-Vila Miguel AngelCodony-Servat JordiCao PengRosell Rafael - Despite being the initial intervention of choice, revascularization for myocardial ischemia-reperfusion (I/R) injury remains constrained, making the exploration of novel therapeutic targets imperative. Alpha-kinase 1 (ALPK1) knockdown mitigates ischemic brain injury, whereas its function in cardiac I/R injury requires further investigation. Nur77 knockout (Nur77 KO) mice, with more severe post-acute myocardial infarction (post-AMI) cardiac dysfunction, fibrosis and hypertrophy than C57BL/6 mice, underwent 45 min LAD ligation plus 4 h reperfusion for modeling and genetic ALPK1 knockdown's impacts on this injury were examined in hypoxic AC16 cardiomyocytes via siRNA silencing, pharmacological ferroptosis rescue and siRNA-resistant ALPK1 plasmid functional recovery assays. The results demonstrated that genetic ALPK1 knockdown resulted in an improvement in cardiac function, the amelioration of pathological changes, a reduction in infarct size, and the suppression of apoptosis of myocardial cells in Nur77 KO mice post-I/R. Furthermore, genetic ALPK1 knockdown was observed to suppress lipid peroxidation and ferroptosis, while concomitantly activating Nrf2/HO-1 pathway in Nur77 KO mice post-I/R. Furthermore, genetic ALPK1 knockdown was observed to inhibit apoptosis and ferroptosis in vitro and pharmacological rescue experiments confirmed ferroptosis as the core downstream cell death pathway of ALPK1. ALPK1 was observed to interact with XPO1, thereby inhibiting XPO1 degradation. Moreover, XPO1 overexpression impeded the impact of ALPK1 knockdown on cell survival, lipid peroxidation, and ferroptosis. ALPK1 represents a potential novel target for pharmacological intervention in the treatment of myocardial I/R injury. - Source: PubMed
Publication date: 2026/08/14
Liu YueHu RuisiWang YantengWang YingxiZhao QiheGuan WenweiWang Difei - Myelodysplastic syndrome with biallelic TP53 inactivation (MDS-biTP53) patients represents an ultra-high-risk subgroup with dismal outcomes. Even after allogeneic hematopoietic stem cell transplantation (allo-HSCT), relapse rates remain extremely high and survival is poor. This preliminary case series reports the outcomes of 8 consecutive patients with MDS-biTP53 who received a novel sequential therapy of decitabine (DAC) combined with the XPO-1 inhibitor selinexor, followed by allo-HSCT at a single center between September 2024 and December 2025. At a median follow-up of 7.3 months (95% CI, 4.2-10.4 months) from HSCT, median overall survival (OS) and relapse-free survival (RFS) were not reached. At last follow-up, 7/8 patients remained alive (OS 87.5%) and 6/8 were relapse-free (RFS 75%), with one relapse (12.5%). This patient successfully achieved a second complete remission following preemptive therapy with low-dose decitabine combined with donor lymphocyte infusion and remained in remission at the last follow-up. Two patients developed serious infections during the peritransplant period. One patient with pre-transplant intestinal colonization of carbapenem-resistant Enterobacteriaceae (CRE) ultimately died due to CRE bloodstream infection followed by intestinal graft-versus-host-disease (GVHD). Overall treatment-related toxicity was deemed manageable, and the incidence of grade III-IV acute GVHD was 25% (2/8). This preliminary study provides encouraging evidence that sequential decitabine and selinexor therapy followed by allo-HSCT may improve outcomes with acceptable toxicity in patients with ultra-high-risk MDS-biTP53. However, these findings are limited by the small sample size, relatively short follow-up, and retrospective, single-center design. Confirmation in larger prospective trials is warranted. - Source: PubMed
Publication date: 2026/08/10
Ren YanlingLang WeiXu YuMei ChenHuang XianboWang ShashaQian JiejingTong Hongyan