R-(-)-gossypol (AT 101) / Ascentage Pharma - LARVOL DELTA

Network-based discovery of tumor-checkpoint inverter drugs targeting pancreatic ductal adenocarcinoma cell states and macrophage reprogramming (AACR 2026) - "Cross-model validation identified state-specific candidate drugs, including Leuprolide, Vinblastine, and Mercaptopurine for GLS; Vindesine, Gossypol, and Binimetinib for MOS; and AT9283, Crizotinib, and Afatinib for PLS. Predicted MR-inversion scores correlated with experimental dose-response profiles in cell lines selected via OncoMatch.Together, these results establish a mechanistic link between tumor-intrinsic transcriptional states and macrophage immunosuppression, while identifying mutation-agnostic, state-specific drugs capable of reprogramming both tumor and immune compartments. This work provides a generalizable framework for network-based drug repurposing to overcome transcriptional plasticity and immune resistance in PDAC."

Oncology • Pancreatic Ductal Adenocarcinoma • APOE

Revealing the Binding Mechanism of Gossypol on Bcl‑2 via Funnel Metadynamics Simulations. (PubMed, ACS Omega) - "Crucially, we demonstrate that gossypol binding reduces the overall flexibility of the binding site and that each binding state is characterized by a unique pattern of conformational stabilization across the four pockets. These findings provide an unprecedentedly detailed and dynamic roadmap of the gossypol-Bcl-2 interaction, offering crucial insights for the future structure-based design of next-generation inhibitors."

Journal • B Cell Lymphoma • Lymphoma • Oncology • BCL2

Overexpression of GhAAP3 increases Helicoverpa armigera feeding by altering hormonal and metabolic composition in cotton. (PubMed, Plant Cell Rep) - "Our findings demonstrate that GhAAP3 negatively regulates cotton resistance against H. armigera by downregulating key defense-related phytohormones and secondary metabolites, while concurrently elevating amino acid and sugar levels. This together impairs the plant's chemical defense and enhances its nutritional suitability for herbivorous pests."

Journal

A Marine Alkaline Protease from Bacillus safensis DL12: Heterologous Expression, Purification and Preliminary Application in Animal Feed. (PubMed, Microorganisms) - "Notably, when hydrolyzing cottonseed meal with purified enzyme versus crude enzyme preparation at equivalent activity, the purified enzyme effectively reduced free gossypol content by 70% compared to the control, achieving more efficient detoxification than the crude enzyme preparation and most reported microbial treatments. These results highlight the potential of B. safensis DL12 protease as a marine-derived enzyme, offering promising prospects for enhancing protein digestibility and addressing the long-standing challenge of gossypol toxicity in cottonseed meal utilization."

Journal

Rational Design of a "Turn-on" Supramolecular Fluorescent Probe for Gossypol Sensing Based on the Restriction of Intramolecular Bending Mechanism. (PubMed, Anal Chem) - "The method exhibited a linear detection range for gossypol from 0-5 μM (R2 = 0.9983) with a response time of under 10 s, achieving satisfactory recovery rates from 80.72 to 119.49% in real pork samples. This work not only provides a tool for food safety monitoring but also offers a systematic and generalizable method, supported by comprehensive computational and experimental evidence, for developing ″turn-on″ supramolecular fluorescent probes."

Journal

Cottonseed proteins: A promising and undervalued non-grain protein source for aquafeed. (PubMed, Anim Nutr) - "Cottonseed protein concentrate is a prime example, obtained through low-temperature solvent extraction, de-gossypolization, and moderate raffinose isolation to enhance its nutritional value and palatability. This review provides a comprehensive overview of the research advancements concerning cottonseed proteins in aquafeed, including a detailed examination of their production processes, physicochemical properties, feed processing characteristics, nutritional values, and a meta-analysis on the growth performance of aquatic animals when cottonseed proteins are used as alternatives to fish meal in feed."

Journal • Review

Electron beam and roasting treatments of cottonseed meal: Implications for gossypol content, rumen degradability parameters and fattening performance in lambs. (PubMed, Appl Radiat Isot) - "Additionally, hot and cold carcass weights (P = 0.02, P = 0.04) and eye muscle width (P = 0.01) were greater in the ICSM group. These results suggest that EB irradiation improves ruminal protein protection and enhances growth performance and carcass quality in fattening lambs."

Journal

Natural Product Modulators of Protein-Protein Interactions: A Comprehensive Review. (PubMed, Phytochem Anal) - "Collectively, these modulators demonstrate PPI druggability and provide chemical probes and lead scaffolds for therapeutic development in cancer, neurodegeneration, infectious disease, and immune disorders."

Journal • Review • CNS Disorders • Immunology • Infectious Disease • Oncology • Targeted Protein Degradation • BCL2 • BCL2L1 • CDC37 • CTNNB1 • HSP90AA1

Exploring natural products as Bcl-2 inhibitors for acute myeloid leukemia therapy using In vitro, STD-NMR spectroscopy, and In silico approaches. (PubMed, Comput Biol Med) - "The three natural products showed potent to significant activity, effectively inducing apoptosis in the HL-60 cell line. Hence, this study identifies three potential lead candidates for drug discovery against Bcl-2-related cancers after further mechanistic and pre-clinical studies."

IO biomarker • Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BAX • CASP3

C1orf35 contributes to high anabolic metabolism by simultaneously promoting aerobic glycolysis and oxidative phosphorylation in multiple myeloma cells. (PubMed, Cancer Gene Ther) - "Our study uncovers a "C1orf35-driven" energy metabolism model in MM cells, providing new insights into the pathogenesis of MM and a potential novel target for the treatment of cancer cells with a high"C1orf35-driven" anabolic metabolism. Schematic diagram of C1orf35 simultaneously promotes glycolysis and OXPHOS."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • LRPPRC • MYC • PKM

Mining Potential Therapeutic Targets for T Cell Exhaustion in Osteoarthritis by Integrating Mendelian Randomization and Single-Cell Sequencing. (PubMed, FASEB J) - "Finally, single-cell analysis highlighted T cells and mast cells as key cell types in OA, with dynamic expression of GPR65 and PLIN2 observed throughout their differentiation. This study identifies GPR65, LDLR, PLIN2, and TRIM14 as biomarkers for OA, offering valuable insights that could support the development of targeted therapies."

Biomarker • Journal • Immunology • Osteoarthritis • Pain • Rheumatology • PLIN2

Correlation of Polymer-drug Composition with Micelle Properties, Performance, and Cytotoxicity for the Oligoelectrolyte-mediated pH-triggered Release of Hydrophobic Drugs. (PubMed, Polymers (Basel)) - "In general, co-encapsulation of OVP and model drugs (doxorubicin (DOX), gossypol (GP), paclitaxel (PX), and 7-ethyl-10-hydroxycamptothecin (SN38)) in the micelles provided good to excellent encapsulation efficiency percentage (EE%) values...However, drug- and OVP-loaded micelles displayed a significant increase in cytotoxicity (up to 8-fold increase) that was independent of the copolymer composition. These results demonstrate the versatility of the oligoelectrolyte-mediated approach to furnish non-responsive micelles with a pH-trigger that allows the rapid release of drugs, regardless of the micelle composition or the drug identity."

Journal • Oncology

Physiological, anatomical, and molecular responses of glanded and glandless cotton to chromium exposure. (PubMed, Front Plant Sci) - "According to the results, it was observed that the antioxidant activity of GhSOD, upregulated 2.5-fold at 100 μM of Cr, plays a key role in mitigating Cr-induced oxidative stress. This study revealed the response mechanism of Cr stress in glanded and glandless cotton that might perform different mechanisms to cope with Cr toxicity."

Journal

Morinda officinalis oligosaccharides improves sperm motility via the gut microbiota and the IGF-1/PI3K/mTOR signaling pathway. (PubMed, Front Endocrinol (Lausanne)) - "MOS and Anaerococcus transplantation activated the IGF-1/PI3K/mTOR pathway, increased Bcl-2, and reduced Cleaved Caspase-3 expression, whereas rapamycin attenuated these improvements, indicating pathway dependence. MOS ameliorates gossypol-induced asthenozoospermia by remodeling the gut microbiota and activating IGF-1/PI3K/mTOR signaling, thereby improving sperm motility and reducing apoptosis. These findings highlight MOS as a promising microbiota-modulating therapeutic strategy for male reproductive dysfunction."

IO biomarker • Journal • Transplantation • BCL2 • CASP3 • IGF1

Preparative Enantiomer Separation of Gossypol as Chloramphenicol Derivative With Cyclodextrin as Chiral Selector by High Speed Countercurrent Chromatography. (PubMed, J Sep Sci) - "The final conditions are 65% methanol content in aqueous phase, 60% ethyl acetate content in organic phase, HP-β-CD concentration was 0.05 mol/L, pH value was 2.37, and temperature was 20°C. The purity of the enantiomers of gossypol acetate is more than 95% (it was calculated by the area normalization method), and the recoveries of gossypol derivatives are between 80% and 90%."

Journal

Efficient separation of gossypol from cotton kernels with copper mediated magnetic molecularly imprinted polymer (PubMed, Se Pu) - "Hence， cottonseed can be safely processed and cottonseed byproducts can be used in animal feed. This study provides a potent tool for the green， fast， and specific separation of high-purity products from plants； the basic research presented herein is both innovative and is potentially industrially applicable."

Journal • Oncology

Gossypol Acetate + FOLFIRI + Bev in mCRC With TP53-Mutant and LRPPRC Positive (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Guiying Wang

New P2 trial • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

Taurine-Modified Gossypol Exerts Dual Anti-Hepatocellular Carcinoma Effects by Inactivating PI3K/AKT Pathway and Targeting FASN-Mediated Lipid Metabolism in Regulatory T Cells. (PubMed, J Hepatocell Carcinoma) - "GT exerts synergistic anti-HCC effects through a dual mechanism: directly suppressing tumor proliferation by inactivating the PI3K/AKT pathway, and remodeling the TIME by targeting FASN-dependent lipid metabolism in Tregs. These findings highlight the potential of GT as a novel multitargeted agent for HCC treatment."

Journal • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor • ANXA5 • FASN

Emerging Non-Thermal Technologies for Reducing Anti-Nutritional Factors in Food Systems: A Systematic Review. (PubMed, J Food Sci) - "The effectiveness of these techniques varies with the food matrix, processing conditions, and specific anti-nutritional compounds. Non-thermal technologies hold promise for developing functional, nutrient-rich foods to meet modern consumer demands."

Journal • Review

Modification of Chitosan with (-)-Gossypol and (-)-Gossypol Acetic Acid Using Free-Radical Grafting Method. (PubMed, Int J Mol Sci) - "The content of GS in polymers raised proportionally with increasing amount of GS added to the reaction mixture, thereby enhancing the ability to scavenge free radicals. The type of GS used (GS or GSA) in polymers affected the degree of CS crosslinking (higher for pure GS), polymer solubility (lower for pure GS), the amount of grafted GS (~20% higher for GSA), and antioxidant properties in favor of GSA."

Journal • Oncology

Cotton gland formation genes GbCGF2/3 positively regulate Verticillium wilt resistance through modulating suberin biosynthesis. (PubMed, New Phytol) - "Additionally, the expression of gossypol biosynthetic genes and defense-related genes PDF1.2 and PR4 in the phytohormone jasmonic acid (JA) pathway is also downregulated in GbCGF2/3-silenced or Cas9-mediated knockout plants. In conclusion, GbCGF2/3 positively regulates Verticillium wilt resistance through promoting suberin biosynthesis, gossypol accumulation and expression of JA signaling defense-related genes, providing a novel insight and strategy for breeding cotton cultivars resistant to Verticillium wilt."

Journal

Engineering seed-specific gossypol-free cotton for human-safe consumption by harnessing the dominant-negative effect of the Gl2e mutation. (PubMed, Plant Commun) - "Notably, completely gossypol-free oil and flour can be produced from SSGF seeds without needing a degossypolization treatment. This work establishes a mechanistic foundation for understanding gland development and offers a sustainable path toward enhancing global plant-derived protein and oil resources."

Journal

Whole cottonseed and palmitic and oleic acid supplementation improve production responses during the immediate postpartum in multiparous dairy cows. (PubMed, J Dairy Sci) - "The absence of a synergistic or additive effect when feeding both WCS and supplemental FA could be attributed to their lack of effect on DMI and reduced digestibility of NDF and FA. In conclusion, these results suggest that both WCS and supplemental FA in the diet can enhance milk production in early-lactation dairy cows, with WCS improving milk fat and protein yields and supplemental FA improving milk fat yield."

Journal

Exploring Ferroptosis-Related Genes in Depression: Insights Into Molecular Mechanisms and Potential Therapies. (PubMed, Int J Gen Med) - "We identified five potential small-molecule compounds (VX-702, gossypol, atomoxetine, TWS-119, and ibudilast) that may target these ferroptosis-related pathways...This study provides evidence supporting the involvement of ferroptosis-related mechanisms in depression and proposes a integrative treatment strategy combining targeted molecular interventions with TCM approaches. The findings offer new perspectives for developing therapeutic interventions, particularly for treatment-resistant depression."

Journal • CNS Disorders • Depression • Inflammation • Mood Disorders • Psychiatry

Gossypol acetate Combined with Bevacizumab and FOLFIRI as Second-Line Therapy for Metastatic Colorectal Cancer with TP53 Mutation and LRPPRC Positivity: A Single-Center, Single-Arm Clinical Study (ChiCTR) - P1 | N=20 | Not yet recruiting | Sponsor: The Second Hospital of Hebei Medical University; The Second Hospital of Hebei Medical University

New P1 trial • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Solid Tumor