xirestomig (ATG-101) / Antengene, Oricell - LARVOL DELTA

Sugar-responsive regulation of an autophagy initiation factor shapes carbon-starvation sensitivity in Arabidopsis. (PubMed, J Exp Bot) - "Association analysis identifies three SNPs in the ATG101 locus linked to the proxy phenotype, and we demonstrate that these polymorphisms differentially affect ATG101 sugar responsiveness and expression during carbon deprivation. Together, our results link natural variation in carbon-deprivation tolerance to regulatory polymorphisms at ATG101, supporting a model in which sugar-responsive control of autophagy initiation shapes genotype-specific sensitivity to carbon starvation in Arabidopsis."

Journal

Reconstitution of multistep recruitment of ULK1 to membranes in autophagy. (PubMed, Sci Adv) - "The human Unc51-like kinase 1 (ULK1) autophagy-initiating complex consists of ULK1, FIP200, and the Hop/Rev7/Mad2 (HORMA) domain heterodimer ATG13:ATG101...The PVP motif is essential for in vitro ULK1 phosphorylation of ATG16L1 and important for autophagy and mitophagy. These data establish a stepwise pathway for recruitment of the ULK1 KD to the vicinity of the membrane surface."

Journal • ATG16L1 • ULK1

Hypoxia-induced EPAS1/HIF2A-USP33-ATG101 axis drives oncogenic autophagy and peritoneal metastasis in gastric cancer. (PubMed, Autophagy) - "Disruption of this axis, either by USP33 silencing or pharmacological inhibition of EPAS1, suppressed autophagy-dependent peritoneal metastasis and prolonged survival in vivo. Collectively, our findings define a mechanistic link between hypoxia, oncogenic autophagy, and peritoneal dissemination in GC, and highlight the EPAS1-USP33-ATG101 axis as a promising therapeutic target in advanced disease."

Journal • Gastric Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • EPAS1

MiR-1 mediates autophagy via ATG14 in sheep Leydig cells infected with Brucella melitensis strain BA0711. (PubMed, Front Vet Sci) - "In the autophagy-animal pathway, ULK1, ATG13, ATG14, PIK3C3, ATG5, ATG101, and ATG16L2 were predicted as the top seven hub DEGs...This study revealed the potential regulatory role of the miR-1-ATG14 axis in this process. These findings provide a novel, cell-specific perspective on the early host-pathogen interactions elicited by B. melitensis within a tissue microenvironment relevant to brucellosis, offering a foundation for future mechanistic studies in more complex systems."

Journal • ATG5 • PIK3C3

Integrated Analysis of Transcriptome and Metabolome Reveals Molecular Responses to Ammonia Stress in the Gills of Litopenaeus vannamei Under Low-Salinity Conditions. (PubMed, Biology (Basel)) - "Integrative multi-omics analysis revealed that L. vannamei mediates stress responses by modulating five core pathways under low-salinity/high-ammonia-nitrogen dual stress: fatty acid degradation and metabolism (e.g., acyl-CoA dehydrogenase short chain (Acads), acetyl-CoA acetyltransferase 2 (ACAT2)), autophagy (e.g., autophagy-related protein 101-like (atg101)), immune regulation pathway (e.g., V-type proton ATPase subunit H-like (VhaSFD), actin-5C-like (Act5C)), metabolic pathway (e.g., molybdopterin synthase catalytic subunit-like (Mocs2B), cytochrome P450 2U1-like (Cyp2b1)), and ABC transporter (e.g., ATP-binding cassette sub-family D member 3-like (ABCD3), ATP-binding cassette sub-family B member 10 (ABCB10)). Through characterization of these core pathways, this study reveals the fundamental mechanisms by which L. vannamei responds to high ammonia nitrogen stress following low-salinity acclimation, providing a theoretical foundation for estuarine shrimp farming."

Journal • ABCD3 • ACAT1 • ATG10 • MOCS2

Functional analysis of Sirt5 in the effect of azadirachtin on the intestinal injury of Spodoptera litura. (PubMed, Pestic Biochem Physiol) - "Functional assays showed that overexpression of Sirt5 in SpLi-221 cells suppressed lysosomal activity under stress, whereas CRISPR/Cas9-mediated knockout (KO) of Sirt5 led to elevated expression of autophagy-related genes (Atg6, Atg16, Atg101) and the apoptosis marker caspase-1...These findings indicate that Sirt5 mitigates azadirachtin-induced midgut damage by modulating autophagy and apoptosis pathways. The present study provides the first experimental evidence linking Sirt5 to host responses against azadirachtin, offering new mechanistic insights into botanical insecticide action and identifying a potential target for enhancing sustainable pest management strategies."

Journal • BECN1 • SIRT5

Targeting the ATG101 And ULK1 complex in pancreatic ductal adenocarcinoma: computational approach (AACR 2025) - "Results suggested that the interaction of ATG101-ULK1 was strong, and hydroxychloroquine reduced this interaction. Site-directed mutagenesis is essential to understanding the molecular interaction (ATG101-ULK2) and the role of residues in PDAC."

Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • ULK1

MicroRNA-451 Modulates Autophagy-Related Signaling with Relevance to Renal Fibrosis in an Accelerated Mouse Model of Diabetic Kidney Disease. (PubMed, Curr Issues Mol Biol) - "miR-451 overexpression attenuates renal fibrosis and modulates autophagy-associated pathways in diabetic kidney disease, independent of metabolic control, highlighting miR-451 as a potential therapeutic target for diabetic kidney disease."

Journal • Preclinical • Diabetes • Diabetic Nephropathy • Fibrosis • Immunology • Metabolic Disorders • Nephrology • Renal Disease • BECN1 • mTOR • YWHAZ

Injectable Zn2+-Driven carrier-free hydrogel via self-assembly of natural small molecules for liver fibrosis therapy through concurrent autophagy activation and ferroptosis inhibition. (PubMed, Mater Today Bio) - "Molecular profiling revealed that ASA Gel upregulated Atg9A and Atg101 in the liver, thereby promoting autophagosome formation, inhibiting P62 expression, and enhancing autophagic flux. Moreover, ASA Gel significantly promoted the expression of GPX4 and SLC7A11 genes, indicating that it inhibited the ferroptosis process in liver tissue. This work establishes a carrier-free hydrogel platform for spatiotemporally coordinated regulation of autophagy and ferroptosis in HSCs."

Journal • Fibrosis • Immunology • Liver Cirrhosis • GPX4 • SLC7A11

PHGDH knockdown activates autophagic flux to suppress migration and invasion of gastric cancer cells. (PubMed, Transl Cancer Res) - "Notably, PHGDH downregulation may indirectly promote the assembly of the ULK1 complex through the concomitant upregulation of FIP200 and ATG101, thereby initiating autophagy. These data suggest that PHGDH plays a role in the progression of GC and may be considered a potential therapeutic target upon further confirmation in larger clinical studies."

Journal • Gastric Cancer • Oncology • Solid Tumor • HIF1A • PHGDH

Mitogen-activated kinase 6 facilitates autophagy initiation to confer salt tolerance in maize. (PubMed, Dev Cell) - "Consistently, mutants lacking ZmMPK6, ZmATG101, or ZmATG11a exhibit compromised autophagy induction and salt tolerance. Thus, this study discovers a fundamental mechanism for autophagy initiation regulation through ATG101 scaffold phosphorylation and defines a MAPK-ATG101-ATG11 module as governing plant salt tolerance."

Journal

Analysis of Migration and Adaptive Evolution in Tibetan Sheep Populations. (PubMed, Animals (Basel)) - "Comparative genomic analyses of populations in cold and arid environments identified several candidate genes related to energy and water homeostasis, as well as hair development (TP53 [Tumor Protein P53], ATG101 [Autophagy Related 101], ATP12A [ATPase H+/K+ Transporting Non-Gastric Alpha2 Subunit], KRT80 [Keratin 80], KRT7 [Keratin 7]). Additionally, Tibetan sheep in the high-altitude arid deserts exhibit stronger adaptive selection for energy homeostasis and water utilization; meanwhile, the HIF-1 [Hypoxia Inducible Factor 1] signaling pathway helps counteract oxidative stress induced by extreme water scarcity in the plateau environment. Our study supports the hypothesis that Tibetan sheep originated in northern China and identifies distinct adaptive features in the Tibetan sheep genome corresponding to their habitats."

Journal • Oncology • ATG10 • HIF1A • KRT7 • KRT80 • RAD50 • TNFA • TNFAIP3 • TP53

Exceptional Response to BTK Inhibitors in Aggressive Lymphomas Linked to Chronic Selective Autophagy (ASH 2023) - "Unexpectedly, we identified multiple autophagy-related genes involved autophagosome formation (ATG9A, ATG101, ATG13, RB1CC1 and ATG14) and autophagosome membrane expansion (ATG2A, WIPI2, WDR45) that strongly counteracted the toxicity of BTKi (≥3 SD)...Collectively, we identified a non-canonical form of selective autophagy that chronically degrades MYD88L265P, is counter-selected in MCD tumors, and is promoted by BTK inhibitors. Our findings help to elucidate the exceptional benefit of BTK-targeted therapies in the MCD DLBCL subtype and offer a rationally designed combination therapy regimen to specifically degrade this mutant allele of MYD88."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BRD4 • CD79B • IRF4 • MYD88 • RB1CC1 • SYK • TLR9

ULK1/2 Inhibitors that Degrade ATG13 Effectively Target KRAS-Mutant Cancers. (PubMed, bioRxiv) - "Previously, we developed small molecule ULK1 inhibitors that not only inhibit ULK kinase activity but also induced the degradation of other core members of the ULK complex including ATG101 and ATG13...Finally, immunohistochemical staining of orthotopic pancreatic tumors reveals a significant increase in CD4⁺ and CD8⁺ T cell infiltration upon treatment, suggesting that SBP-1750 enhances anti-tumor immunity. These findings support further development of SBP-1750 as a novel ATG-targeting cancer therapy."

Journal • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD4 • CD8 • KRAS

Reconstitution of multistep recruitment of ULK1 to membranes in autophagy. (PubMed, bioRxiv) - "Human ULK1C consists of ULK1 itself, FIP200, and the HORMA domain heterodimer ATG13:ATG101...Biochemical reconstitution and cell-based assays show that the PVP motif is essential for in vitro ULK1 phosphorylation of ATG16L1 and important for BNIP3/NIX-dependent mitophagy. These data establish a stepwise pathway for recruitment of the ULK1 KD to the vicinity of the membrane surface downstream of PI3KC3-C1."

Journal • ATG16L1 • ULK1

RAN Promotes Autophagy and Malignant Progression of Lung Adenocarcinoma through ATG101. (PubMed, Adv Biol (Weinh)) - "Suppression of ATG101 effectively counteracts the enhanced proliferation induced by RAN overexpression, highlighting ATG101 as a key mediator of RAN's effects. This study underscores the critical molecular dynamics of LUAD driven by RAN, suggesting that the RAN-ATG101 axis can serve as a novel therapeutic target."

Journal • Lung Adenocarcinoma • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Antengene Hosts 2025 R&D Day Showcasing Encouraging Clinical Data and Solid Progress with Investigational Programs (The Malaysian Reserve) - "...it will present the latest data and future plans for three mid/late-stage clinical programs, including ATG-022 (CLDN18.2 antibody-drug conjugate [ADC]), ATG-037 (oral CD73 small molecule inhibitor), and ATG-101 (PD-L1/4-1BB bispecific antibody). The company will also share the latest progress on ATG-125 (B7H3 x PD-L1 bispecific ADC): A B7H3 x PD-L1 targeted therapy featuring “'O + ADC' dual-effect molecules for the treatment of solid tumors and its AnTenGager™ T-cell engager (TCE) technology platform which incorporates steric hindrance masking, along with updates on several key preclinical programs."

Clinical data • Colorectal Cancer • Hematological Malignancies • Melanoma • Neuroendocrine Carcinoma • Non Small Cell Lung Cancer • Ovarian Cancer

High Tumor Mutational Burden Associates with Increased CD8 T-Cell Presence, Decreased Tumor Heterogeneity, and Increased AICDA Expression in an HIV-Inclusive Cohort of Diffuse Large B-Cell Lymphoma (ASH 2024) - "TMB-high tumors had increased expression of tumor-promoting autophagy-related genes (ATG101, ATG3), and purine and pyrimidine metabolism genes (POLR1C, CDA, NME1)...This study highlights the interplay between genomic complexity, intrinsic tumor features and immune response in DLBCL. Our findings may lead to new therapeutic avenues for DLBCL patients regardless of HIV status, though further work must be done to elucidate the role of AICDA and systemic immunity on tumorigenesis and anti-tumor response."

Heterogeneity • Tumor mutational burden • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • AICDA • ATG3 • CD8 • DDB2 • IFNGR1 • IRF1 • LIG1 • LRIG1 • POLH • POLR1D • STAT1 • TMB

Lnc-HZ14 promotes LLPS-mediated SPHK1 aggrephagy degradation to suppress trophoblast cell proliferation in unexplained recurrent miscarriage. (PubMed, Autophagy) - "Meanwhile, lnc-HZ14 also promotes autophagy by activating ETV4-mediated transcription of ATG101 and PPP1R15A/GADD34...As for miscarriage treatment, therapeutic upregulation of SPHK1 by treatment with phorbol 12-myristate 13-acetate (PMA), an SPHK1 agonist recovers mouse placental proliferation and alleviates mouse miscarriage. Collectively, this study shows for the first time the regulatory roles of lnc-HZ14, LLPS, and aggrephagy degradation of SPHK1 in unexplained recurrent miscarriage, uncovering novel pathogenesis and biological mechanisms of unexplained RM and also providing potential targets for treatment against miscarriage."

Journal • Targeted Protein Degradation • ETV4 • PPP1R15A • SPHK1 • SQSTM1

Revisiting the evolution of the yeast Atg1 complex. (PubMed, Autophagy Rep) - "In contrast, the fission yeast Schizosaccharomyces pombe Atg1 complex incorporates Atg101 instead of Atg29 and Atg31 and features a rod-shaped Atg17 scaffold. Collectively, our findings delineate the potential evolutionary trajectories of the Atg1 complex in yeast. Abbreviations: ATG, autophagy-related; BLAST, basic local alignment search tool; C-Mad2, closed Mad2; EAT, Early Autophagy Targeting/Tethering; EM, electron microscopy; His-MBP, histidine-maltose binding protein; HORMA, Hop1, Rev7, and Mad2; IDR, intrinsically disordered region; O-Mad2, open Mad2; iTOL, Interactive Tree of Life; PAS, phagophore assembly site; PI3K, phosphatidylinositol 3-kinase; PMSF, phenylmethylsulfonyl fluoride; pTM, predicted template modeling; RMSD, root mean square deviation; TOR, target of rapamycin; TORC1, TOR complex 1."

Journal • CNS Disorders • Psychiatry • Schizophrenia

Evolutionary diversification of the autophagy initiation complex: reduced Atg101 dependency and changes in Atg9 binding to Atg13. (PubMed, Autophagy) - "Furthermore, both KpAtg101 and KpAtg31 are involved in Atg1 complex assembly in K. phaffii. These findings suggest that the reduced importance of Atg101 in the Atg13-Atg9 interaction and Atg1 complex assembly enabled the eventual loss of ATG101 in some Holomycota species, including S. cerevisiae."

Journal • RB1CC1 • ULK1

A Trial of ATG-101 in Patients With Metastatic/Advanced Solid Tumors and Mature B-cell Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1 | N=33 | Terminated | Sponsor: Antengene (Hangzhou) Biologics Co., Ltd. | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2025 ➔ Mar 2025 | N=62 ➔ 33 | Trial completion date: Dec 2025 ➔ Mar 2025; The sponsor has decided to adjust the development strategy of the investigational drug in this study.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

The neuroprotective role of chlorogenic acid and Fisetin in differentiated neuronal cell line-SHSY5Y against amyloid-β-induced neurotoxicity. (PubMed, Toxicol In Vitro) - "Autophagy-related pathways were significantly modulated which was evidenced by increased PRKAA1 (AMPK) and decreased MTOR mRNA levels, alongside elevated expression of ATG101, ATG13, ULK1, SQSTM1 (p62) and reduced ATG5 levels. Furthermore, our docking studies also revealed good Fisetin and CGA binding affinity within AMPK and mTOR's binding pocket (FKBP12-FRB). Although the neuroprotective effects of CGA and Fisetin are underscored by transcriptional and docking studies, further translational and biophysical validation is required to demonstrate their therapeutic efficacy against AD-related neurodegeneration."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Pain • AMPK • ATG5 • DLG4 • MFN2 • mTOR • PINK1 • SQSTM1 • SYP

Caloric restriction mimetics chlorogenic acid and fisetin as potential autophagy inducers targeting ATG101. (PubMed, Biochem Biophys Rep) - "Therefore, these CRMs can be responsible for their potential as autophagy inducers. These findings offer significant insights into the molecular processes through which CRMs may improve neurodegenerative diseases by triggering autophagy."

Journal • Alzheimer's Disease • CNS Disorders • ULK1

The triad interaction of ULK1, ATG13, and FIP200 is required for ULK complex formation and autophagy. (PubMed, Elife) - "In mammals, autophagosome formation, a central event in autophagy, is initiated by the ULK complex comprising ULK1/2, FIP200, ATG13, and ATG101...We validated the predicted interactions by point mutations and demonstrated direct triad interactions among ULK1, ATG13, and FIP200 in vitro and in cells, wherein each interaction was additively important for autophagic flux. These results indicate that the ULK1-ATG13-FIP200 triadic interaction is crucial for autophagosome formation and provides a structural basis and insights into the regulation mechanism of autophagy initiation in mammals."

Journal • ULK1