vatalanib (PTK787) / Novartis, Bayer - LARVOL DELTA

Rare quinochalcone C-glycosides with vasoprotective activities from Carthamus tinctorius L. (PubMed, Bioorg Chem) - "CETSA and DARTS assays confirmed the direct interaction between 2 and AAMP, and molecular dynamics simulations revealed moderate conformational rearrangements upon binding. Further studies revealed that 2 rescued PTK787-impaired intersegmental and subintestinal vessels in a dose-dependent manner in vivo."

Journal • Cardiovascular • Myocardial Ischemia • Reperfusion Injury • AAMP • CD31 • PECAM1

Screening and characterization of pro-angiogenic peptides from Spirulina: computer simulation, experimental validation, and mechanistic insights. (PubMed, Front Pharmacol) - "In zebrafish models, five of these peptides, MFDCLR, MDMWGK, MNPGCR, MYDNFCK, and MPGLGR, significantly stimulated subintestinal vessel plexus (SIVP) growth and rescued intersegmental vessel (ISV) injury induced by Vatalanib (PTK787)...Subsequent mechanistic investigations revealed that the pro-angiogenic effect of MDMWGK was associated with activation of the VEGFA/PI3K-Akt signaling pathway, as evidenced by increased phosphorylation of PI3K and Akt. Collectively, this study provides an integrated screening strategy for discovering bioactive peptides from Spirulina and establishes a theoretical basis for developing pro-angiogenic agents."

Journal

Sodium 2-mercaptobenzothiazole induces vascular developmental toxicity in zebrafish (Danio rerio) involving Kdr/PI3K/Akt signaling. (PubMed, Ecotoxicol Environ Saf) - "In addition, PTK787 co-treatment partially attenuated MBTNa-induced vascular abnormalities and reversed selected transcriptional alterations. These findings suggest that Kdr/PI3K/Akt-associated signaling is involved in MBTNa-induced vascular developmental toxicity and highlight the need to include vascular endpoints in the risk assessment of benzothiazole-related contaminants."

Journal • Cardiovascular • KDR

Exploring the pro-angiogenic constituents of Lagopsis supina and their mechanisms via transcriptome analysis, molecular docking and RT-qPCR validation. (PubMed, Fitoterapia) - "supina 60% ethanol-water extract) were screened, of which 15 showed angiogenesis-promoting activity, were screened in a PTK787-induced vascular injury zebrafish model...In contrast, LS22 downregulated extracellular matrix-related adhesion molecules and itga2b, while upregulating thbs1a and integrin itgb3b. In conclusion, the L. supina constituents LS21 and LS22 that are primarily phenolic acids and phenylpropanoids, exert their angiogenesis-promoting effects mainly via modulating cell adhesion and suppressing TGF-β signaling pathway."

Journal • CDH5 • ITGA2B • NCOR1 • PECAM1 • SMAD2 • TGFB1

Investigating the Pro-Angiogenic Mechanism of Diammonium Glycyrrhizinate Injection in Zebrafish via Transcriptomic Analysis and RT-qPCR Validation. (PubMed, J Appl Toxicol) - "A zebrafish vascular injury model induced by PTK787 was used to assess the pro-angiogenic effect of GA preparations...GA preparations have an obvious pro-angiogenic effect, in which DGI exerts particularly strong activity, appearing to be mediated mainly by activation of the mTOR/HIF-1 signaling pathway. This study broadens the clinical application of GA agents and provides new insights into the pharmacodynamics and potential mechanisms of DGI as a candidate agent for treating ischemic diseases."

Journal • Cardiovascular • Hepatology • Myocardial Ischemia • Peripheral Arterial Disease • HIF1A

"Overcoming endothelial cell anergy by VEGFR2 inhibition to enhance CAR T-cell response in aggressive B-cell lymphoma" (DGHO 2025) - "To overcome endothelial cell anergy and thereby, resistance against CAR T cell therapy, we hypothesized that combining VEGFR2 inhibitor PTK787 and CAR T cells displays synergistic treatment effects.Materials and To elucidate mechanisms associated with CAR T cell resistance in patients with aggressive B cell lymphoma, we applied multiomic analyses to pre- and post CAR T cell treatment lymphoma specimens... To conclude, our in vivo results strongly suggest that combining CD19 directed CAR T cells and VEGFR2 inhibition is a promising strategy to improve treatment efficacy of CAR T cell therapy, potentially increasing outcome of patients with aggressive B cell lymphoma."

CAR T-Cell Therapy • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma

Overcoming endothelial cell anergy by VEGFR2 inhibition to enhance CAR T cell response in aggressive B cell lymphoma (ITOC 2025) - "Anergic endothelial cells form a physical barrier between tumor cells and circulating CAR T cells, keeping them confined to the vascular system and thereby, leading to reduced efficacy of CAR T cells.3 4 To overcome endothelial cell anergy and thereby, resistance against CAR T cell therapy, we hypothesized that combined VEGFR2 inhibition through PTK787 and CAR T cells displays synergistic treatment effects...Strikingly, in an autochthonous aggressive B cell lymphoma mouse model we demonstrate a significantly prolonged overall and progression free survival of mice treated with VEGFR2 inhibition in combination with murine CD19-CAR T cells. Conclusions To conclude, our in vivo results strongly suggest that combining CD19 directed CAR T cells and VEGFR2 inhibition is a promising strategy to improve treatment efficacy of CAR T cell therapy, potentially increasing outcome of patients with aggressive B cell lymphoma."

CAR T-Cell Therapy • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A hyaluronic acid nanogels based exosome production factory for tumor photothermal therapy and angiogenesis inhibition. (PubMed, Int J Biol Macromol) - "In this work, based on the endocyto-fusion-exocytosis pathway of exosome formation, a multifunctional hyaluronic acid nanogel loaded with the antiangiogenic drug vatalanib and the near-infrared photothermal agent indocyanine green (ICG) was designed...Anti-angiogenic signals in intracellular vesicles were then delivered to vascular endothelial cells by exosomes through membrane fusion and exocytosis, which inhibited tumor angiogenesis to prevent tumor proliferation and metastasis. Cell experiments and tumor models demonstrate that our therapeutic strategy can achieve effective tumor inhibition."

Journal • Oncology

An AI-driven strategy for active compounds discovery and non-destructive quality control in traditional Chinese medicine: A case of Xuefu Zhuyu Oral Liquid. (PubMed, Talanta) - "Secondly, the pro-angiogenesis effects of XZOL were evaluated in a PTK787-induced intersegmental vessels (ISVs) injury zebrafish model...This system effectively distinguished expired and normal samples by combining Hotelling T2 and Distance to Model X (DModX) statistics of multivariate statistical process control (MSPC), and accurately predicted the content of above active compounds by CNN model integration with bidirectional long short-term memory (Bi-LSTM) and multi-head self-attention (MHSA) networks. This study underscores the potential of AI-driven strategy to enhance TCM standardization and global recognition by providing an active compounds-based holistic quality control strategy of TCM."

Journal

Discovery of key molecular signatures for diagnosis and therapies of glioblastoma by combining supervised and unsupervised learning approaches. (PubMed, Sci Rep) - "Finally, we recommended KGs-guided four repurposable drug molecules (Fluoxetine, Vatalanib, TGX221 and RO3306) against GBM through molecular docking, drug likeness, ADMET analyses and molecular dynamics simulation studies. Thus, the discoveries of this study could serve as valuable resources for wet-lab experiments in order to take a proper treatment plan against GBM."

Biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • AURKA • CCNB2 • CDCA8 • CDK1 • CHEK1 • MCM10 • RAD51 • RAD51AP1 • TOP2A

Targeting Myeloid Cells in Head and Neck Squamous Cell Carcinoma: A Kinase Inhibitor Library Screening Approach. (PubMed, Int J Mol Sci) - "Among the promising inhibitors tested, vatalanib, a VEGF-R inhibitor, demonstrated significant in vivo efficacy at inhibiting tumor growth and reducing tumor-associated myeloid cells, thereby underscoring its potential as a therapeutic agent. Our findings highlight specific kinase inhibitors with differential modulatory effects on HNSCC-associated myeloid subsets and caution the application of some as anti-cancer drugs. This experimental system may provide a robust platform for identifying new agents targeting tumor-associated myeloid cells in HNSCC and beyond, and for elucidating mechanistic insights into tumor-myeloid cell interaction."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ITGAM

In Vitro Assessment of Inhibitory Effects of Kinase Inhibitors on CYP2C9, 3A and 1A2: Prediction of Drug-Drug Interaction Risk with Warfarin and Direct Oral Anticoagulants. (PubMed, Eur J Pharm Sci) - "Our results suggest that several kinase inhibitors, including vatalanib and linsitinib, can cause CYP-mediated drug-drug interactions with warfarin and, to a lesser extent, with apixaban and rivaroxaban. The work provides mechanistic insights into the risk of DDIs between kinase inhibitors and anticoagulants, which can be used to avoid preventable DDIs in the clinic."

Journal • Preclinical • CYP2C9

Endothelial to mesenchymal transition enhances permissiveness to AAV vectors in cardiac endothelial cells. (PubMed, Mol Ther) - "Among the top drugs increasing AAV-mediated transduction we found vatalanib, an inhibitor of multiple tyrosine kinase receptors...In vivo injection of AAV vectors in the heart after myocardial infarction resulted in the selective transduction of cells undergoing endothelial to mesenchymal transition, which is known to happen transiently after cardiac ischemia. Collectively, these results point to endothelial to mesenchymal transition as a mechanism improving AAV transduction in cardiac endothelial cells, with implications for both basic research and the induction of therapeutic angiogenesis in the heart."

Journal • Cardiovascular • Coronary Artery Disease • Gene Therapies • Myocardial Infarction • Myocardial Ischemia

The natural compound sinometumine E derived from Corydalis decumbens promotes angiogenesis by regulating HIF-1/ VEGF pathway in vivo and in vitro. (PubMed, Biomed Pharmacother) - "Furthermore, it promoted angiogenesis in PTK787-induced, MPTP-induced, and atorvastatin-induced vessel injury models of zebrafish, while also suppressing hypoxia-induced locomotor impairment in zebrafish. In conclusion, our study profiled the angiogenic activities of SE in vitro and in vivo. The key targets and related pathways involved in anti-ischemic effects of SE, shedding light on the pharmacodynamic components and mechanisms of Corydalis decumbens, and provides valuable insights for identifying effective substances for the treatment of ischemic stroke."

Journal • Preclinical • Cardiovascular • Ischemic stroke • Reperfusion Injury • HIF1A • KDR

Analysis of vascular disruption in zebrafish embryos as an endpoint to predict developmental toxicity. (PubMed, Arch Toxicol) - "By exposing embryos to multiple tyrosine kinase inhibitors including SU4312, SU5416, Sorafenib, or PTK787, we confirmed that this method can detect concentration-dependent inhibition of angiogenesis. One of the test compounds was showing particularly high specificity for angiogenesis effects (SU4312) and was, therefore, suggested as a model compound for the identification of molecular markers of angiogenic disruption. Our findings establish video imaging in wild-type strains as viable, non-invasive, high-throughput method for the detection of chemical-induced angiogenic disruption in zebrafish embryos."

Journal • Cardiovascular • KDR

Hyperipersions A-C, three new acylphloroglucinols from the branches and leaves of Hypericum perforatum L. with antiangiogenic activities. (PubMed, Nat Prod Res) - "Their antiangiogenic activities were studied against HUVECs. The IC value of compound 3 was 2.39 ± 0.21 μM against HUVECs, which was stronger than vatalanib, and other compounds had moderate antiangiogenic activity."

Journal

The Immune-microenvironment Confers Chemoresistance in Breast cancer through activation of VEGFR2/STAT3/BIRC5 signaling (ESMO-IO 2023) - P1 | "In a first-in-human study (NCT00358163, NCT00731861), Vatalanib (PTK787/ZK) was well tolerated alone or in combination with paclitaxel. Conclusions Together, our study revealed the role of TAMs in conferring paclitaxel resistance in breast cancer. Combinatorial VEGFR2 blockade and paclitaxel chemotherapy decreased TAM population and showed better prognostic outcomes in breast cancer."

Breast Cancer • Oncology • Solid Tumor • BIRC5 • KDR

Traditional Chinese Medicine formula, Sanwujiao granule, attenuates ischemic stroke by promoting angiogenesis through early administration. (PubMed, J Ethnopharmacol) - "These results demonstrate that SW plays a critical role in anti-IS via promoting angiogenesis through early administration, indicating that SW is a candidate herbal complex for further investigation in treating IS in the clinical."

Journal • Cardiovascular • CNS Disorders • Ischemic stroke • CD31 • IGF1 • PECAM1

Machine learning model for anti-cancer drug combinations: Analysis, prediction, and validation. (PubMed, Pharmacol Res) - "Our prediction and validation results indicated that the combination of the RTK inhibitors Lapatinib and Pazopanib exhibited a strong therapeutic effect in breast cancer by blocking the downstream PI3K/AKT/mTOR signaling pathway. Furthermore, we incorporated molecular features to identify potential biomarkers for synergistic drug pairs, and almost all potential biomarkers found connections between drug targets and corresponding molecular features using protein-protein interaction network. Overall, this study provides valuable insights to complement and guide rational efforts to develop drug combination treatments."

Journal • Machine learning • Breast Cancer • Oncology • Solid Tumor

Inhibition of VEGFR2 and EGFR signaling cooperatively suppresses the proliferation of oral squamous cell carcinoma. (PubMed, Cancer Med) - "VEGFR-mediated signaling would be an alternative signaling pathway for the survival of OSCC cells under the disruption of EGFR signaling. These results highlight the clinical application of VEGFR inhibitors in the development of multi-molecular-targeted therapeutics against OSCC."

Journal • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • KDR

Inactive mutated VEGFR2 promotes melanoma growth via heterodimerization with wild-type receptor (EACR 2023) - "Also, the expression of VEGFR2R1032Q increases melanoma cell resistance to the VEGFR2-targeted TKi linifanib and vatalanib.Remarkably the R1032Q substitution of VEGFR2 occurs in a hot-spot residue of the kinase domain which is recurrently mutated in many other receptor tyrosine kinases (RTKs), including EGFR, KIT, FLT3, FLT4 and PDGFRA, among others. Therefore, our results anticipate the effects and druggability of all other uncharacterized mutations corresponding to the substitution R1032Q of VEGFR2.ConclusionOur data reveal a possible ligand-independent inter-receptor kinase activation of VEGFR2/VEGFR2R1032Q heterodimers which drives tumor progression. This novel mechanism of activation of VEGFR2, which may be shared by other RTKs, could be exploited to develop new therapeutic approaches to treat tumors harboring the VEGFR2R1032Q mutation and possibly all other corresponding ones."

Melanoma • Oncology • Solid Tumor • FLT3 • FLT4 • KDR • PDGFRA

Xinkeshu tablets promote angiogenesis in zebrafish embryos and human umbilical vein endothelial cells through multiple signaling pathways. (PubMed, J Ethnopharmacol) - "Herein, we identified 116 chemical constituents of XKS for the first time and demonstrated that XKS may regulate angiogenesis through multiple signaling pathways to treat CHD."

Journal • Cardiovascular • Coronary Artery Disease • Heart Failure

The 5-lipoxygenase/cyclooxygenase-2 (5-LOX/COX-2) cross-over metabolite, hemiketal E, enhances VEGFR2 activation and promotes angiogenesis. (PubMed, J Biol Chem) - "HKE-mediated effects in vitro and in vivo were blocked by the VEGFR2 inhibitor vatalanib, indicating that the pro-angiogenic effect of HKE was mediated by VEGFR2...In summary, our studies indicate that biosynthetic cross-over of the 5-LOX and COX-2 pathways gives rise to a potent lipid autacoid that regulates endothelial cell function in vitro and in vivo. These findings suggests that common drugs targeting the arachidonic acid pathway could prove useful in anti-angiogenic therapy."

Journal • PTPN1

In silico prediction and biological assessment of novel angiogenesis modulators from traditional Chinese medicine. (PubMed, Front Pharmacol) - "In the absence of PTK787, deoxycholic acid and ursodeoxycholic acid did not affect angiogenesis. Despite some limitations, these results suggest further refinements of in silico prediction combined with biological assessment will be a valuable platform for accelerating the research and development of natural products from traditional Chinese medicine and understanding their mechanisms of action, and also for other traditional medicines for the prevention and treatment of angiogenic diseases."

Journal • Age-related Macular Degeneration • Cardiovascular • Macular Degeneration • Myocardial Infarction • Oncology • Ophthalmology • Retinal Disorders

Kunxian Capsule Extract Inhibits Angiogenesis in Zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway. (PubMed, Chin J Integr Med) - "KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VEGF pathway and showed promising potential for RA treatment."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Osteoporosis • Rheumatoid Arthritis • Rheumatology • AKT1 • FGF2