- |||||||||| vatalanib (PTK787) / Novartis, Bayer
"Overcoming endothelial cell anergy by VEGFR2 inhibition to enhance CAR T-cell response in aggressive B-cell lymphoma" (S / T (Confex)) - Nov 5, 2025 - Abstract #DGHO2025DGHO_1528;
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.
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Journal: A hyaluronic acid nanogels based exosome production factory for tumor photothermal therapy and angiogenesis inhibition. (Pubmed Central) - Feb 21, 2025
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.
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Journal: Targeting Myeloid Cells in Head and Neck Squamous Cell Carcinoma: A Kinase Inhibitor Library Screening Approach. (Pubmed Central) - Nov 27, 2024
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.
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Journal: Endothelial to mesenchymal transition enhances permissiveness to AAV vectors in cardiac endothelial cells. (Pubmed Central) - Nov 13, 2024
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.
- |||||||||| semaxanib (SU5416) / Pfizer, vatalanib (PTK787) / Novartis, Bayer
Journal: Analysis of vascular disruption in zebrafish embryos as an endpoint to predict developmental toxicity. (Pubmed Central) - Jan 18, 2024
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.
- |||||||||| Votrient (pazopanib) / Novartis, BeiGene, vatalanib (PTK787) / Novartis, Bayer
Journal, Machine learning: Machine learning model for anti-cancer drug combinations: Analysis, prediction, and validation. (Pubmed Central) - Aug 21, 2023
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.
- |||||||||| TriptoSar (triptolide) / Pierre Fabre, vatalanib (PTK787) / Novartis, Bayer
Journal: Kunxian Capsule Extract Inhibits Angiogenesis in Zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway. (Pubmed Central) - Dec 16, 2022
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. KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VEGF pathway and showed promising potential for RA treatment.
- |||||||||| AiTan (rivoceranib) / HLB Bio Group, vatalanib (PTK787) / Novartis, Bayer, motesanib (AMG 706) / Takeda
Journal: Effects of multi-kinase inhibitors on the activity of cytochrome P450 2J2. (Pubmed Central) - Oct 18, 2022
In simulations of docking to CYP2J2, the U energy values of apatinib, motesanib, and vatalanib were low, and measured -84.5, -69.9, and -52.3 kcal/mol, respectively.4. In conclusion, apatinib, motesanib, and vatalanib strongly inhibited CYP2J2 activity, suggesting that the effects of a given CYP2J2 substrate may be altered upon the administration of these MKIs.
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Journal: Tetramethylpyrazine Protects Endothelial Injury and Antithrombosis via Antioxidant and Antiapoptosis in HUVECs and Zebrafish. (Pubmed Central) - Jul 30, 2022
In vivo experiments showed that TMP restored PTK787-induced damage to intersegmental vessels (ISVs) in Tg(fli-1: EGFP)y1 transgenic (Flik) zebrafish larvae...RT-qPCR assay proved that TMP could inhibit the expression of fga, fgb, fgg, f7, and von Willebrand factor (vWF) mRNA to exert an antithrombotic effect. Our findings suggest that TMP can contribute to endothelial injury protection and antithrombosis by modulating MAPK signaling and attenuating oxidative stress and antiapoptosis.
- |||||||||| Avastin (bevacizumab) / Roche, vatalanib (PTK787) / Novartis, Bayer
Preclinical, Journal: Impact of Anti-Angiogenic Treatment on Bone Vascularization in a Murine Model of Breast Cancer Bone Metastasis Using Synchrotron Radiation Micro-CT. (Pubmed Central) - Jul 29, 2022
At T2, only the bone vasculature was reduced in the combined AAD-treatment group (p < 0.05), as judged by measurement of the blood vessel thickness. Our data suggest that, at the early stage, combined AAD treatment dampens tumor-induced bone resorption with no detectable effects on bone vessel organization while, at a later stage, it affects the structure of bone microvascularization.
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Journal: Promoting Angiogenesis Effect and Molecular Mechanism of Isopropyl Caffeate (KYZ), a Novel Metabolism-Derived Candidate Drug, Based on Integrated Network Pharmacology and Transgenic Zebrafish Models. (Pubmed Central) - Jun 22, 2022
Our data suggest that, at the early stage, combined AAD treatment dampens tumor-induced bone resorption with no detectable effects on bone vessel organization while, at a later stage, it affects the structure of bone microvascularization. These data show that KYZ may promote angiogenesis through VEGF, PI3K/AKT, and MEK/ERK signaling pathways, suggesting that KYZ exhibited great potential in the treatment of ischemic cardio-cerebrovascular diseases.
- |||||||||| NSC23766 / University of Oslo, vatalanib (PTK787) / Novartis, Bayer
Review, Journal, IO biomarker: Overexpressed or hyperactivated Rac1 as a target to treat hepatocellular carcinoma. (Pubmed Central) - May 26, 2022
Our analysis underlines the prominent oncogenic functions of Rac1 in HCC and discuss the modalities to target this small GTPase. Rac1 shall be considered as a valid target to limit the acquired and intrinsic resistance of HCC tumors and their metastatic potential.
- |||||||||| Avastin (bevacizumab) / Roche, vatalanib (PTK787) / Novartis, Bayer, Nexavar (sorafenib) / Bayer, Amgen
Preclinical, Journal: In Vitro Angiogenesis Inhibition and Endothelial Cell Growth and Morphology. (Pubmed Central) - Apr 30, 2022
Additionally, several nuclear receptor ligands and miscellaneous compounds that might affect EC growth and differentiation were tested, but only dexamethasone gave rise to cluster formation similarly to VEGF-neutralizing compounds. These results point to a link between angiogenesis, HUVEC differentiation and glucocorticoid receptor activation.
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Enrollment change, Trial termination: Trial of PTK787/ZK 222584 Plus Paclitaxel (clinicaltrials.gov) - Apr 29, 2022
P1, N=7, Terminated,
These results point to a link between angiogenesis, HUVEC differentiation and glucocorticoid receptor activation. N=10 --> 7 | Active, not recruiting --> Terminated
- |||||||||| Journal: Machine learning-driven identification of drugs inhibiting cytochrome P450 2C9. (Pubmed Central) - Feb 22, 2022
Metabolism assays allowed the characterization of specific metabolites of abemaciclib, cloperidone, vatalanib and tarafenacin produced by CYP2C9. The obtained results demonstrate that such a strategy could improve the prediction of drug-drug interactions in clinical practice and could be utilized to prioritize drug candidates in drug discovery pipelines.
- |||||||||| Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
Journal: Multiparameter Evaluation of the Platelet-Inhibitory Effects of Tyrosine Kinase Inhibitors Used for Cancer Treatment. (Pubmed Central) - Dec 18, 2021
Dasatinib and sunitinib dose-dependently reduced collagen-induced aggregation in PRP and washed platelets; pazopanib, cabozantinib, and vatalanib inhibited this response in washed platelets only; and fostamatinib, axitinib, and lapatinib showed no/limited effects...Dasatinib, fostamatinib, sunitinib, and pazopanib interfered in early collagen receptor-induced molecular-signaling compared with cabozantinib and vatalanib. Fostamatinib, sunitinib, pazopanib, and vatalanib may be promising for future evaluation as antiplatelet drugs.
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Enrollment change, Trial termination: PTK/ZK in Disseminated Malignant Melanoma (clinicaltrials.gov) - Oct 6, 2021
P2, N=9, Terminated,
However, these modifications led to new phthalazine derivatives with higher VEGFR-2 inhibitory activities than vatalanib and which are nearly equipotent to sorafenib. N=30 --> 9 | Suspended --> Terminated; Substance was withdrawn from further development.
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Preclinical, Journal: The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice. (Pubmed Central) - Jul 9, 2021
In addition, vatalanib reduced the number and area of Aβ plaques in the cortex in 5xFAD mice. Our results suggest that vatalanib has potential as a regulator of AD pathology.
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Journal: New Prenylated Indole Homodimeric and Pteridine Alkaloids from the Marine-Derived Fungus Aspergillus austroafricanus Y32-2. (Pubmed Central) - May 27, 2021
Each compound was evaluated for pro-angiogenic, anti-inflammatory effects in zebrafish models and cytotoxicity for HepG2 human liver carcinoma cells. As a result, compounds 2, 4, 5, 7, 10 exhibited pro-angiogenic activity in a PTK787-induced vascular injury zebrafish model in a dose-dependent manner, compounds 7, 8, 10, 11 displayed anti-inflammatory activity in a CuSO-induced zebrafish inflammation model, and compound 6 showed significant cytotoxicity against HepG2 cells with an IC value of 30 µg/mL.
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Journal: Inhibitory Effects of Euphorbia ebracteolata Hayata Extract ECB on Melanoma-Induced Hyperplasia of Blood Vessels in Zebrafish Embryos. (Pubmed Central) - May 20, 2021
The results showed that ECB was an active ingredient of EEH in inhibiting melanoma-induced hyperplasia of blood vessels in zebrafish embryos, similar to the angiogenic inhibitor vatalanib...Both vegfr2 and vegfr3 are essential genes that regulate blood vessel formation and upregulate the expression of p53 and casp3a genes in zebrafish. Together, the above-mentioned results indicate that ECB has a potential antimelanoma effect in vivo, which may be mediated by inhibiting vascular endothelial growth factor receptors.
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Journal: Tanshinol borneol ester (DBZ), a novel synthetic small molecule angiogenesis stimulator inspired by botanical formulations for angina pectoris. (Pubmed Central) - Aug 30, 2020
The effects of DZB on HUVEC proliferation, EB permeability, R2* and fBV are consistent with an anti-angiogenic component to the compound’s mechanism of action that may facilitate clinical activity against some solid tumors. These data revealed, for the first time, that DBZ promoted multiple key steps of angiogenesis, at least in part through Akt and MAPK signalling pathways, and suggest it may be potentially developed further for treating myocardial infarction and other cardiovascular diseases.
- |||||||||| Biomarker, Clinical, Journal: Microparticles from VEGF inhibitor-treated cancer patients mediate endothelial cell injury. (Pubmed Central) - May 13, 2020
Plasma MPs were isolated from cancer patients before and after treatment with VEGFi (pazopanib, sunitinib, or sorafenib)...Endothelial cells exposed to post-VEGFi treatment ECMPs induced an increase in pre-pro-ET-1 mRNA expression, corroborating the increase in endothelin-1 (ET-1) production in HAEC stimulated with vatalanib (VEGFi)...Our findings define novel molecular mechanism involving interplay between microparticles, the ET-1 system and endothelial cell pro-inflammatory and redox signaling, which may be important in cardiovascular toxicity and hypertension associated with VEGFi anti-cancer treatment. Our novel data identify MPs as biomarkers of VEGFi-induced endothelial injury and important mediators of ET-1-sensitive redox-regulated pro-inflammatory signaling in effector endothelial cells, processes that may contribute to cardiovascular toxicity in VEGFi-treated cancer patients.
- |||||||||| Mozobil (plerixafor) / Sanofi, DC101 / Eli Lilly, vatalanib (PTK787) / Novartis, Bayer
Preclinical, Journal: HIF prolyl hydroxylase inhibitor FG-4497 enhances mouse hematopoietic stem cell mobilization via VEGFR2/KDR. (Pubmed Central) - Feb 7, 2020
VEGFR2 was absent on mesenchymal and hematopoietic cells and was detected only in Sca1 endothelial cells in the BM. We propose that HIF PHD inhibitor FG-4497 enhances HSPC mobilization by stabilizing HIF-1α in HSPCs as previously demonstrated, as well as by activating VEGFR2 signaling in BM endothelial cells, which facilitates HSPC egress from the BM into the circulation.
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Journal: Cinnamaldehyde accelerates wound healing by promoting angiogenesis via up-regulation of PI3K and MAPK signaling pathways. (Pubmed Central) - Mar 29, 2019
...In vivo, CA partially restored intersegmental vessels in zebrafish pretreated with PTK787, which is a selective inhibitor for vascular endothelial growth factor receptor (VEGFR)...The potential mechanism involves activation of the PI3K/AKT and MAPK signaling pathways. Such a small non-peptide molecule may have clinical applications for promoting therapeutic angiogenesis in chronic diabetic wounds and myocardial infarction.
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Trial completion date, Trial primary completion date: Vatalanib and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors (clinicaltrials.gov) - Feb 6, 2018
P1, N=44, Active, not recruiting,
Such a small non-peptide molecule may have clinical applications for promoting therapeutic angiogenesis in chronic diabetic wounds and myocardial infarction. Trial primary completion date: Dec 2017 --> Dec 2018 | Trial completion date: Dec 2017 --> Dec 2018
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Trial completion, Trial primary completion date: Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors (clinicaltrials.gov) - Jan 17, 2018
P1, N=96, Completed,
Trial primary completion date: Dec 2017 --> Dec 2018 | Trial completion date: Dec 2017 --> Dec 2018 Active, not recruiting --> Completed | Trial primary completion date: Dec 2017 --> Sep 2009
- |||||||||| vatalanib (PTK787) / Novartis, Bayer
Trial primary completion date: Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors (clinicaltrials.gov) - Mar 22, 2017
P1, N=96, Active, not recruiting,
Active, not recruiting --> Completed | Trial primary completion date: Dec 2017 --> Sep 2009 Trial primary completion date: Dec 2016 --> Dec 2017
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