Cilcane (cilengitide) / Iceni Pharma - LARVOL DELTA

Lost in translation: Do preclinical studies predict clinical failure in GBM? (SNO 2025) - "For the trials evaluated, no preclinical brain:plasma (B/P) data were reported for enzastaurin, cilengitide, nimotuzumab, Depatux-M, or bevacizumab, although IgG typically has a B/P ≈1%...The best response for each drug compared to relevant control (relative increase in median survival) was 22% (nimotuzumab), 31% (marizomib), 36% (sunitinib CD) / 5% (sunitinib PD), 63% (bevacizumab/temozolomide), 140% (imatinib), 157% (Depatux-M), 220% (veliparib/temozolomide), 300% (cediranib); median survival was not reached for cilengitide...The stunning lack of clinical progress in GBM is deeply discouraging, but is consistent with underwhelming preclinical testing and the contextual interpretation of those results. Acknowledging multifaceted reasons for failed clinical trials, a more rigorous and critical approach should be used in preclinical studies, coupled with follow-up surgical window of opportunity studies, to identify and promote only the most promising therapies into..."

Preclinical • Brain Cancer • CNS Disorders • Glioblastoma • Solid Tumor

Lost in translation: Do preclinical studies predict clinical failure in GBM? (SNO 2025) - "For the trials evaluated, no preclinical brain:plasma (B/P) data were reported for enzastaurin, cilengitide, nimotuzumab, Depatux-M, or bevacizumab, although IgG typically has a B/P ≈1%...The best response for each drug compared to relevant control (relative increase in median survival) was 22% (nimotuzumab), 31% (marizomib), 36% (sunitinib CD) / 5% (sunitinib PD), 63% (bevacizumab/temozolomide), 140% (imatinib), 157% (Depatux-M), 220% (veliparib/temozolomide), 300% (cediranib); median survival was not reached for cilengitide...The stunning lack of clinical progress in GBM is deeply discouraging, but is consistent with underwhelming preclinical testing and the contextual interpretation of those results. Acknowledging multifaceted reasons for failed clinical trials, a more rigorous and critical approach should be used in preclinical studies, coupled with follow-up surgical window of opportunity studies, to identify and promote only the most promising therapies into..."

Preclinical • Brain Cancer • CNS Disorders • Glioblastoma • Solid Tumor

Lost in translation: Do preclinical studies predict clinical failure in GBM? (WFNOS 2025) - "For the trials evaluated, no preclinical brain:plasma (B/P) data were reported for enzastaurin, cilengitide, nimotuzumab, Depatux-M, or bevacizumab, although IgG typically has a B/P ≈1%...The best response for each drug compared to relevant control (relative increase in median survival) was 22% (nimotuzumab), 31% (marizomib), 36% (sunitinib CD) / 5% (sunitinib PD), 63% (bevacizumab/temozolomide), 140% (imatinib), 157% (Depatux-M), 220% (veliparib/temozolomide), 300% (cediranib); median survival was not reached for cilengitide...The stunning lack of clinical progress in GBM is deeply discouraging, but is consistent with underwhelming preclinical testing and the contextual interpretation of those results. Acknowledging multifaceted reasons for failed clinical trials, a more rigorous and critical approach should be used in preclinical studies, coupled with follow-up surgical window of opportunity studies, to identify and promote only the most promising therapies into..."

Preclinical • Brain Cancer • CNS Disorders • Glioblastoma • Oncology • Solid Tumor

Lost in translation: Do preclinical studies predict clinical failure in GBM? (WFNOS 2025) - "For the trials evaluated, no preclinical brain:plasma (B/P) data were reported for enzastaurin, cilengitide, nimotuzumab, Depatux-M, or bevacizumab, although IgG typically has a B/P ≈1%...The best response for each drug compared to relevant control (relative increase in median survival) was 22% (nimotuzumab), 31% (marizomib), 36% (sunitinib CD) / 5% (sunitinib PD), 63% (bevacizumab/temozolomide), 140% (imatinib), 157% (Depatux-M), 220% (veliparib/temozolomide), 300% (cediranib); median survival was not reached for cilengitide...The stunning lack of clinical progress in GBM is deeply discouraging, but is consistent with underwhelming preclinical testing and the contextual interpretation of those results. Acknowledging multifaceted reasons for failed clinical trials, a more rigorous and critical approach should be used in preclinical studies, coupled with follow-up surgical window of opportunity studies, to identify and promote only the most promising therapies into..."

Preclinical • Brain Cancer • CNS Disorders • Glioblastoma • Glioma • Oncology • Solid Tumor

Disrupting integrin signaling impairs migration, MYC-driven purine biosynthesis, and stemness in H3K27M diffuse midline gliomas (SNO 2025) - "Promisingly, co-treatment with anti-ITGB1 antibody and cilengitide (ITGB3/5 inhibitor) further improved survival and resulted in 75% long-term survivors, free of disease. Strikingly, this combinatorial strategy failed to confer any survival benefit in adult glioblastoma (H3WT) models. Overall, these findings highlight integrin targeting as a promising therapeutic avenue in H3K27M-DMG, capable of disrupting tumor-specific migration, MYC-driven purine biosynthesis, and stemness programs."

Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Solid Tumor • ARVA • CRKL • FERMT2 • IMPDH2 • ITGB1 • ITGB3 • ITGB5 • MYC • PTK2

Disrupting integrin signaling impairs migration, MYC-driven purine biosynthesis, and stemness in H3K27M diffuse midline gliomas (SNO 2025) - "Promisingly, co-treatment with anti-ITGB1 antibody and cilengitide (ITGB3/5 inhibitor) further improved survival and resulted in 75% long-term survivors, free of disease. Strikingly, this combinatorial strategy failed to confer any survival benefit in adult glioblastoma (H3WT) models. Overall, these findings highlight integrin targeting as a promising therapeutic avenue in H3K27M-DMG, capable of disrupting tumor-specific migration, MYC-driven purine biosynthesis, and stemness programs."

Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Solid Tumor • ARVA • CRKL • FERMT2 • IMPDH2 • ITGB1 • ITGB3 • ITGB5 • MYC • PTK2

RUNX2, IBSP, and SPP1 as Key Molecular Nodes in Calcific Aortic Stenosis: Transcriptomic Diagnostics and Emerging Therapeutic Targets. (AHA 2025) - "MEK inhibitors (trametinib, selumetinib) downregulate RUNX2 via MAPK/ERK pathway inhibition. Epigenetic modulators (vorinostat, valproic acid) could suppress RUNX2 transcriptionally. The integrin antagonist cilengitide blocks αvβ3, disrupting IBSP/SPP1-mediated signaling. While these agents are approved for oncology or neurology, their utility in valve calcification remains investigational.In summary, this study highlights RUNX2, IBSP, and SPP1 as transcriptomic biomarkers and actionable therapeutic targets in CAS. Their expression profiles, biological roles, and druggability make them high-priority candidates for future diagnostic tools and targeted interventions in a disease currently reliant on surgical replacement."

Cardiovascular • Immune Modulation • Immunology • RUNX2 • SPP1

Disrupting integrin signaling impairs migration, MYC-driven purine biosynthesis, and stemness in H3K27M diffuse midline gliomas (WFNOS 2025) - "Promisingly, co-treatment with anti-ITGB1 antibody and cilengitide (ITGB3/5 inhibitor) further improved survival and resulted in 75% long-term survivors, free of disease. Strikingly, this combinatorial strategy failed to confer any survival benefit in adult glioblastoma (H3WT) models. Overall, these findings highlight integrin targeting as a promising therapeutic avenue in H3K27M-DMG, capable of disrupting tumor-specific migration, MYC-driven purine biosynthesis, and stemness programs."

Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Solid Tumor • ARVA • CRKL • FERMT2 • IMPDH2 • ITGB1 • ITGB3 • ITGB5 • MYC • PTK2

Disrupting integrin signaling impairs migration, MYC-driven purine biosynthesis, and stemness in H3K27M diffuse midline gliomas (WFNOS 2025) - P2 | "Promisingly, co-treatment with anti-ITGB1 antibody and cilengitide (ITGB3/5 inhibitor) further improved survival and resulted in 75% long-term survivors, free of disease. Strikingly, this combinatorial strategy failed to confer any survival benefit in adult glioblastoma (H3WT) models. Overall, these findings highlight integrin targeting as a promising therapeutic avenue in H3K27M-DMG, capable of disrupting tumor-specific migration, MYC-driven purine biosynthesis, and stemness programs."

Brain Cancer • Diffuse Midline Glioma • Glioblastoma • Glioma • Solid Tumor • ARVA • CRKL • FERMT2 • IMPDH2 • ITGB1 • ITGB3 • ITGB5 • MYC • PTK2

Critical Role of the Endothelial αV/β5 Integrin Receptor Signaling Pathway in Promoting Irisin-induced Hippocampal BDNF Expression. (PubMed, Mol Neurobiol) - "Our findings indicated that recombinant irisin (r-irisin) treatment of hippocampal slices led to an increase in BDNF expression and that this effect was blocked by cilengitide, an αV/β5 integrin antagonist...Additionally, αV/β5 integrins, phosphorylated endothelial NO synthase (p-eNOS), and BDNF were significantly elevated in the hippocampal endothelial cells of exercised rats. These findings reveal that irisin may upregulate BDNF expression in the hippocampal through a mechanism dependent on endothelial αV/β5 integrins and the FAK/eNOS signaling pathway, supporting its potential as a therapeutic target for enhancing NO-dependent BDNF expression."

Journal • NOS3

Proteomic Analysis of Thyroid Hormone-Induced Secretome in Cutaneous T Cell Lymphoma (ASH 2024) - "This study aims to determine and contrast the proteins secreted (i) under basal conditions and (ii) in the presence of THs with or without the integrin αVβ3 pharmacological inhibitor, cilengitide (cile)...In summary, our study has shed light on the crucial role of THs as regulators of HuT78 and MJ secretome. These findings are of significant importance, as they provide a solid basis for further investigation into the role of these soluble factors and their receptors in the CTCL microenvironment."

IO biomarker • Omic analysis • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • BCL2L1 • CDK1 • HIF1A • IL2 • ITGB3 • MAPK14 • PD-1 • PD-L1 • PSMA1 • SLC2A1 • TGFB1 • THY1 • TLN1 • UCHL5 • VAV1 • ZAP70

Spatial-reprogramming derived GPNMB+ macrophages interact with COL6A3+ fibroblasts to enhance vascular fibrosis in glioblastoma. (PubMed, Genome Med) - "Our findings highlight the critical role of COL6A3+ TAFs in regulating MDM function and spatial distribution, as well as their contribution to fibrotic tumor vasculature formation. Additionally, we propose targeting COL6A3+ TAFs with cilengitide as a potential therapeutic strategy."

Journal • Brain Cancer • Fibrosis • Glioblastoma • Immunology • Oncology • Solid Tumor • COL6A3 • GPNMB • ITGB5

Chemoselective sulfonyl fluoride exchange (SuFEx)-induced macrocyclization of tyrosine-containing peptides in aqueous media. (PubMed, Chem Sci) - "To demonstrate the scope and translational potential of the method, STEMtide analogs of several clinically relevant peptides, including leuprorelin, β-MSH, liraglutide, and cilengitide, a cyclic RGD peptidomimetic, were successfully synthesized in high yield using the SuFEx-mediated strategy. RGD STEMtide analogs exhibited low toxicity to MCF-7 cells, as well as potent inhibition of cell adhesion comparable to cilengitide itself, highlighting the therapeutic potential of this new class of peptide macrocycles."

Journal

Transcriptome-Based Identification of Biomarkers Associated With Sphingosine-1-Phosphate Signaling Pathway in Aortic Dissection. (PubMed, Int J Hypertens) - "Finally, seven potential small-molecule drugs targeting ITGA5 were predicted, including cilmostim, cilengitide, and dimethyl sulfoxide. This study identifies ITGA5 as a novel biomarker for S1P-associated AD and reveals its potential underlying mechanisms and therapeutic candidates, providing a theoretical foundation for AD diagnosis and treatment."

Biomarker • Journal • CD4 • CXCL5 • ITGA5

The Integrin Inhibitor Cilengitide Targets CCN1-Mediated Angiogenesis and Reduces Disease Severity in a Preclinical Rheumatoid Arthritis Model (ACR Convergence 2025) - "Cilengitide effectively inhibits CCN1-induced angiogenesis in vitro, confirming that CCN1 exerts its effects on endothelial cells through integrins αvβ3 and αvβ5. In vivo, Cilengitide significantly reduces clinical, structural, and histological damage in the Tg197 arthritis model while modulating immune profiles. These findings suggest that CCN1's effects in RA, including structural and inflammatory damage, are mediated by its role in promoting pathological angiogenesis."

IO biomarker • Preclinical • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CCN1 • CD4 • PD-1

B3GNT2 Regulates Integrin β3 Glycosylation and Th17/Treg Imbalance in Axial Spondyloarthritis Pathogenesis (ACR Convergence 2025) - "This study demonstrates that rs6759298 reduces B3GNT2 gene expression, thereby altering the glycosylation of ITGB3 and promoting the progression of AS. These findings offer new insights into the immune mechanisms underlying AS."

Ankylosing Spondylitis • Immunology • Inflammation • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis • ITGB3

TGFβ enhances platelet-breast-cancer-cell interaction and promotes platelet aggregation. (PubMed, FEBS J) - "Furthermore, we selected specific inhibitors of integrin-αv (cilengitide) and galectin-3 (GB1107) that did not interfere with PLT aggregation itself...Complementary analyses of proteomic datasets from breast cancer tissues demonstrated a significant positive correlation between TGFβ1 and the platelet marker integrin alpha-IIb (ITGA2B; also known as CD41), particularly in luminal A subtypes and in cancers with lymph node involvement. These findings suggest that TGFβ stimulation enhances PLT-breast-cancer cell interactions and promotes PLT aggregation through the upregulation of specific adhesion proteins, thereby potentially contributing to CAT and metastatic progression."

Journal • Breast Cancer • Cardiovascular • Hematological Disorders • Oncology • Solid Tumor • Thrombosis • ITGA2B • TGFB1

KIF1Bβ suppresses hepatocellular carcinoma by transporting and secreting FBLN5 to attenuate the integrin pathway. (PubMed, Gut) - "Our findings shed light on the genetic and molecular mechanisms of the HCC-associated susceptibility locus at 1p36.22 and provide potential new strategies for the treatment of HCC."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • KIF1B

Fibrinogen αC-Domain Derived From Group 1 Allergen of Dermatophagoides microceras Modulates Cell Adhesion in Human Bronchial Epithelial Cells. (PubMed, Proteins) - "Functional validation using Cilengitide, a cyclic RGD peptide that antagonizes αVβ3 and αVβ5 integrins, confirmed that the pro-adhesive effects were integrin αV-dependent. These findings reveal that Der m 1 not only cleaves fibrinogen but also produces bioactive fragments that influence epithelial adhesion and signaling, offering new insight into airway remodeling in allergic asthma."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Integrin αV Emerges as a Potential Therapeutic Target with Cautionary Implications in Thoracic Aortic Aneurysm and Dissection. (PubMed, J Thorac Cardiovasc Surg) - "These findings identify integrin αV as a promising molecular target for TAA intervention. However, they also highlight concerns regarding the clinical use of integrin αV inhibitors, which are currently under investigation in cancer trials, as they may increase the risk of TAA or AD development."

Journal • Cardiovascular • Oncology • STAT1

Penetrative biomimetic nanovehicle boosts immunotherapy in triple-negative breast cancer via SOS1 blockade. (PubMed, Asian J Pharm Sci) - "Herein, we developed a biomimetic liposomal platform (CCM/Cil-lipo@TD), which integrates cilengitide (Cil)-functionalized breast cancer cell membranes (CCM) to co-deliver tetrandrine (TET) and low-dose docetaxel (DTX) for TNBC therapy. The CCM/Cil-lipo@TD exerted superior tumor inhibition (82.9 %) in 4T1 orthotopic models and effectively inhibited postoperative local recurrence and distant metastasis. Taken together, the Cil-engineered, cell membrane-anchoring CCM/Cil-lipo@TD provides a promising approach for TNBC immunotherapy."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Inhibition of integrin alpha V reduces inflammation and the transition to heart failure after pressure overload. (PubMed, Biochem Pharmacol) - "CD51 expression and CD51+ cell infiltration were analyzed, and the functional relevance was tested using the CD51 inhibitor cilengitide...CD51 contributes to the immune-fibrotic axis driving heart failure progression under pressure overload. Pharmacological inhibition of CD51 reduces cardiac fibrosis and dysfunction while modulating pro-inflammatory CD51+ myeloid cells, offering a novel therapeutic strategy for pressure overload-induced heart failure."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Inflammation • Myocardial Infarction • CCR2

Endothelial αvβ3 integrin induction during hypoxia protects blood-brain barrier integrity. (PubMed, Proc Natl Acad Sci U S A) - "In young (8 to 10 wk) and aged (20 mo) mice, we examined the impact of a function-blocking β3 integrin antibody as well as the inhibitory peptide cilengitide on BBB disruption during exposure to CMH (8% O2)...These observations suggest that hypoxic induction of endothelial αvβ3 integrin enhances BBB integrity by stabilizing endothelial adhesion. This raises the interesting possibility that pharmacological upregulation of endothelial αvβ3 integrin in the aged brain might hold therapeutic promise for vascular dementia."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

Non-genomic stimulatory effect of T3 on calcium dynamics in GnRH neurons via integrin αVβ3. (PubMed, Endocrinology) - "In contrast, the blockade of membrane αVβ3 integrins (with cilengitide) prevented the T3-induced increase in GnRH neurons calcium peak frequency...In sum, these results demonstrate for the first time a direct effect of thyroid hormones on GnRH neuronal activity, with T3 stimulating calcium oscillations through the non-genomic αVβ3 integrin pathway. Understanding this thyroid-reproductive axis interaction will help clarify the mechanisms linking thyroid dysfunction to reproductive disorders and pave the way for targeted therapeutic interventions."

Journal • Endocrine Disorders

ITGA5-Expressing Tumor Cells Interact with Schwann Cells to Drive Nerve Growth Factor-Mediated Immunosuppression of NK Cells. (PubMed, Mol Ther) - "Additionally, Cilengitide significantly improves anti-PD-1 immunotherapy efficacy, offering a potential therapeutic strategy to counteract PNI-driven immunosuppression. This study identifies ITGA5 as a key promoter of tumor invasion into nerves, enhancing NGF release from Schwann cells and altering the immune landscape to favor tumor growth. These findings open new avenues for therapies targeting these interactions in cancer progression."

IO biomarker • Journal • Immunology • Oncology • IFNG • ITGA5