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

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."

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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%."

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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."

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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."

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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."

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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

A dirigent protein redirects extracellular terpenoid metabolism for defense against biotic challenges. (PubMed, Nat Commun) - "Notably, mutants lacking these dirigent proteins produce gossypol but are devoid of hemigossypolone and heliocides in green organs exhibit heightened susceptibility to multiple biotic stresses, underscoring the enhanced protective role of these metabolites. This study describes a DPs-mediated mechanism of extracellular hydroxylation and highlights the potential ecological advantages of redirecting specialized metabolism extracellularly for enhanced defense against varying types of pathogens and herbivores."

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Cytotoxicity, antioxidant activity, and gene expression effects of gossypol in primary smooth muscle of myometrium from Ovis aries (PSMo24) cells. (PubMed, Reprod Biol) - "In conclusion, gossypol induces dose-dependent cytotoxicity in uterine smooth muscle cells (PSMo24), modulating structural, hormonal, and apoptotic genes without altering basal antioxidant activity. Low concentrations were well tolerated, while higher doses from 7 µg/mL activated pro-apoptotic pathways The results highlight the need for caution in reproductive contexts within the animal field and suggest potential use in oncological therapies."

IO biomarker • Journal • BAX • BCL2 • ER • MYLK • PGR

Structure, tautomerism, and radical scavenging activity of Schiff bases and hydrazones of gossypol. (PubMed, Phys Chem Chem Phys) - "Some of them are 4 times more effective than caffeic acid in their radical scavenging properties. The modification of gossypol by introducing amines and hydrazines containing groups capable of reacting with free radicals allows obtaining promising and highly effective radical scavenging agents."

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Targeting Steroid Receptor Coactivators for the Treatment of Benign Female Reproductive Disorders. (PubMed, Endocr Connect) - "To inhibit SRC activity, natural compounds (e.g., gossypol, bufalin, verrucarin A) and synthetic small molecules (e.g., SI-2, SI-12, MCB-613) have been developed, demonstrating preclinical efficacy across several human diseases...This review summarizes current knowledge of SRC biology in benign gynecologic disorders, outlines their mechanistic roles in disease progression, and highlights opportunities for clinical translation. Targeting SRCs may ultimately represent a novel, non-hormonal, fertility-preserving therapeutic strategy in women's health."

Journal • Endometriosis • Gynecology • Immunology • Polycystic Ovary Syndrome • Solid Tumor • Uterine Leiomyoma • Women's Health • NCOA3

Screening of a Gossypol-Removing Yeast Strain and Characterization of Its Removal Mechanism. (PubMed, Microorganisms) - "Assessment of gossypol removal activity revealed that strain ZYS-3 predominantly removes gossypol through the secretion of extracellular enzymes targeting specific active groups (phenolic hydroxyl groups and aldehyde groups) within the gossypol molecule. These enzymes facilitate oxidation and elimination reactions, leading to the opening of the naphthalene ring and subsequent removal of gossypol."

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Gossypol acetic acid affects locomotor activity by inducing mitophagy-related ferroptosis and apoptosis in zebrafish. (PubMed, Toxicol Sci) - "The in vitro study using PC12 cells also showed that GAA could induce mitochondrial membrane potential rise, ROS generation, apoptosis and ferroptosis. These results indicate that GAA affects locomotor activity by disrupting the nervous system and muscle in zebrafish, and its toxicity is closely related to mitochondria dysfunction, oxidative stress, apoptosis and ferroptosis."

Journal • Oncology

Biochemical and metabolic responses of cotton variety XLZ54 to Thrips tabaci and screening of resistance characterization indicators. (PubMed, Pest Manag Sci) - "This study indicates that XLZ54 has the highest resistance to T. tabaci, and this is closely related to its low nutrient content and its high amounts of insect-resistant substances such as flavonoids, total phenols, gossypol, and tannins after damage. In addition, the seven indicators mentioned above can serve as characterization indices for evaluating the resistance of cotton to T. tabaci, providing a basis for future breeding of cotton varieties resistant to T. tabaci."

Journal • CAT

CRISPR/Cas9-mediated mutation of GhCAD decreases the gossypol content of cottonseed. (PubMed, J Biol Eng) - "Furthermore, we characterized GhMYC2-D09 as a transcription factor that increases gossypol biosynthesis. These findings may provide new insights to further elucidate the regulatory network of gossypol biosynthesis."

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