VEGFR Inibitori (VEGFR Inhibitors)

Altro Protein Tyrosine Kinase Inibitori

Prodotti selettivi di isoforme

• Inibitori in evidenza
• Inibitori (105)
• Sostanze chimiche (2)

N. Cat.	Nome del prodotto	Informazioni	Citazioni di utilizzo del prodotto	Validazioni del prodotto
S2842	SAR131675	SAR131675 è un inibitore di VEGFR3 con IC50/Ki di 23 nM/12 nM in saggi acellulari, circa 50 e 10 volte più selettivo per VEGFR3 rispetto a VEGFR1/2, con scarsa attività contro Akt1, CDK, PLK1, EGFR, IGF-1R, c-Met, Flt2 ecc.	Cell Death Discov, 2025, 11(1):320 Zool Res, 2025, 46(6):1317-1325 Cell Signal, 2025, 130:111675
S1010	BIBF 1120 (Nintedanib)	Nintedanib è un potente triplo inibitore dell'angiokinasi per VEGFR1/2/3, FGFR1/2/3 e PDGFRα/β con IC50 di 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM e 59 nM/65 nM in saggi privi di cellule. Fase 3.	Cancer Biology & Medicine, November 19, 2025, 20250275 Thorax, February 18, 2026, thorax-2025-223325 Drug Design, Development and Therapy, February 18, 2022, 397-411
S1119	Cabozantinib (XL184)	Un potente inibitore di VEGFR2 con IC50 di 0,035 nM, Cabozantinib (XL184) inibisce anche c-Met, Ret, Kit, Flt-1/3/4, Tie2 e AXL con IC50 di 1,3 nM, 4 nM, 4,6 nM, 12 nM/11,3 nM/6 nM, 14,3 nM e 7 nM in saggi senza cellule, rispettivamente. Induce apoptosi PUMA-dipendente nelle cellule di cancro al colon tramite la via di segnalazione AKT/GSK-3β/NF-κB.	Cell Reports Medicine, September 20, 2022, 100659 Redox Biology, October 21, 2023, 102945 Hepatology Communications, November 8, 2023, e0313
S1164	E7080 (Lenvatinib)	Lenvatinib è un inibitore multi-target, principalmente per VEGFR2(KDR)/VEGFR3(Flt-4) con IC50 di 4 nM/5,2 nM, meno potente contro VEGFR1/Flt-1, circa 10 volte più selettivo per VEGFR2/3 contro FGFR1, PDGFRα/β in saggi acellulari. Lenvatinib (E7080) inibisce anche FGFR1-4, PDGFR, Kit (c-Kit), RET (c-RET), e mostra potenti attività antitumorali. Fase 3.	Int J Biol Sci, 2026, 22(7):3617-3634 Cancer Sci, 2026, 117(1):257-271 J Hepatocell Carcinoma, 2026, 13:572919
S1005	Axitinib (AG-013736)	Axitinib è un inibitore multi-bersaglio di VEGFR1, VEGFR2, VEGFR3, PDGFRβ e c-Kit con IC50 di 0,1 nM, 0,2 nM, 0,1-0,3 nM, 1,6 nM e 1,7 nM rispettivamente nelle cellule endoteliali dell'aorta suina.	J Exp Zool B Mol Dev Evol, 2026, 346(1):7-19 Cancer Cell, 2025, S1535-6108(25)00070-4 Chem Biol Interact, 2025, 418:111628
S7667	SU 5402	SU5402 è un potente inibitore di Protein Tyrosine Kinase multi-bersaglio con IC50 di 20 nM, 30 nM e 510 nM per VEGFR2, FGFR1 e PDGF-Rβ, rispettivamente.	Exploration (Beijing), 2026, 6(2):70160 Int J Mol Sci, 2025, 26(8)3536 Basic Clin Pharmacol Toxicol, 2025, 136(5):e70022
S8401	Erdafitinib (JNJ-42756493)	Erdafitinib è un potente e selettivo inibitore pan- fibroblast growth factor receptor (FGFR) biodisponibile per via orale con potenziale attività antineoplastica. Questo composto si lega anche a RET (c-RET), CSF-1R, PDGFR-α/PDGFR-β, FLT4, Kit (c-Kit) e VEGFR-2 e induce l'apoptosi cellulare.	Commun Biol, 2025, 8(1):394 Int J Mol Sci, 2025, 26(8)3525 J Clin Invest, 2024, 134(2)e169241
S7397	Sorafenib (BAY 43-9006)	Sorafenib è un inibitore multichinasico di Raf-1 e B-Raf con IC50 di 6 nM e 22 nM in saggi acellulari, rispettivamente. Sorafenib inibisce VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 e c-KIT con IC50 di 90 nM, 20 nM, 57 nM, 59 nM e 68 nM, rispettivamente. Sorafenib induce autophagy e apoptosis e attiva la ferroptosis con attività antitumorale.	J Hepatocell Carcinoma, 2026, 13:572919 Mol Cancer, 2025, 24(1):34 Nat Commun, 2025, 16(1):509
S1029	CC-5013 (Lenalidomide)	Lenalidomide è un inibitore della secrezione di TNF-α con IC50 di 13 nM nelle PBMC. Lenalidomide (CC-5013) è un ligando dell'ubiquitin E3 ligase cereblon (CRBN) e provoca l'ubiquitinazione selettiva e la degradazione di due fattori di trascrizione linfoidi, IKZF1 e IKZF3, da parte dell'ubiquitin ligase CRBN-CRL4. Lenalidomide promuove l'espressione della cleaved caspase-3 e inibisce l'espressione del VEGF e induce l'apoptosis.	Signal Transduct Target Ther, 2025, 10(1):29 Nat Commun, 2025, 16(1):3800 Cell Rep Med, 2025, S2666-3791(25)00102-8
S1490	Ponatinib (AP24534)	Ponatinib è un nuovo, potente inibitore multi-bersaglio di Abl, PDGFRα, VEGFR2, FGFR1 e Src con IC50 di 0,37 nM, 1,1 nM, 1,5 nM, 2,2 nM e 5,4 nM in saggi senza cellule, rispettivamente. Ponatinib (AP24534) inibisce l'autophagy.	J Cell Mol Med, 2026, 30(4):e71053 Cancers (Basel), 2026, 18(7)1082 Nat Commun, 2025, 16(1):471
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Solid tumors require the growth and dissemination of blood vessels and lymphatic vessels to support the metastatic growth of cancers. Following the recognition of growth factor receptor pathways that regulate angiogenesis, a number of small molecular inhibitors and antibodies have been developed that target the activity of vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) pathway. This includes oral small-molecule tyrosine kinase inhibitors currently in clinical practice, namely sunitinib and sorafenib. These are commonly used in the treatment algorithm for renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC), two indications that are known to develop resistance to conventional chemotherapeutics.

The VEGFs include five known structurally-related mammalian ligands (VEGFA, VEGFB, VEGFC, VEGFD, and placenta growth factor, PLGF). The VEGFs are disulfide-bonded homodimers, however, VEGFA and PLGF heterodimers are also known to exist. Due to alternative splicing or due to processing, VEGF ligands occur as several different variants. As a result, these variants bind differently to both VEGFRs and to co-receptors resulting in different biological responses including angiogenesis, lymphangiogenesis, permeability, inflammatory cell recruitment and fatty acid uptake. VEGFs are produced by several different cell types and act in a paracrine manner. The VEGFs bind to three structurally related tyrosine kinases (VEGFR1, VEGFR2, and VEGFR3). Modulating the effect of the VEGFRs are a number of co-receptors that lack intrinsic catalytic activity (i.e. heparin sulfate, neurophilins and integrins) and bind to VEGF.^[1]

VEGFR1 (also known as Fms-like tyrosine kinase 1, Flt1, in mice) is a single-transmembrane glycoprotein structurally related to VEGFR2 and VEGFR3. VEGFR1 is expressed at high levels in vascular endothelial cells, and along with VEGFR2 binds to VEGFA. VEGFR1 is noted to bind exclusively to VEGFB and PIGF. Expression of VEGFR1 is noted to occur during vessel growth and remodeling activity. Non-endothelial cells that express VEGFR1 includes monocytes and macrophages, human tropholblasts, renal mesangial cells, vascular smooth muscle cells, dendritic cells and various tumor cells. A key regulator of VEGFR1 gene expression is hypoxia.^[1]

VEGFR2 (also known as KDR; kinase insert domain receptor, in the human and Flk1; fetal liver kinase-1, in mice) binds VEGFA with a 10-fold lower affinity than VEGFR1.  Other targets of VEGFR2 include proteolytically processed VEGFC and VEGFD. The only known ligand to uniquely bind to VEGFR2 is the open reading frame-encoded VEGFE. VEGFR2 is expressed in most adult vascular endothelial cells as well as circulating endothelial progenitor cells, pancreatic duct cells, retinal progenitor cells, megakaryocytes and hematopoietic cells. VEGFR2 expression is induced in conjunction with active angiogenesis (i.e. the uterus during the reproductive cycle) and in pathological process related to neovascularization (i.e. cancer). VEGFR2, often in combination with VEGFR3, is expressed at significantly upregulated levels in the tumor vascular endothelium in most common human solid tumors. Tumor cells can also express VEGFR2, however, epithelial and mesenchymal tumor cells typically express VEGFR1 rather than VEGFR2. Nevertheless, increased expression of VEGFR2  on tumor cells has been noted for melanoma and hematological malignancies. And, there is evidence supporting a relationship between chronic inflammation and tumor development.^[1]

VEGFR3 (also known as Fms-like tyrosine kinase 4, Flt4 in the mouse) is activated by the binding of VEGFC or VEGFD, once these two ligands undergo proteolytic processing (this increases their affinity to VEGFR2 and VEGFR3). In addition, hVEGFD shows similar affinity to both VEGFR2 and VEGFR3, while mVEGFD binds only to VEGFR3. During embryogenesis, VEGFR3 expression occurs in the primary vascular plexus at day E8.5. In late stages of embryogenesis, VEGFR3 is expressed in venous endothelial cells of the cardinal vein, that results in VEGFR3-expressing lymphatics. Postnatally, VEGFR3 plays an important role in lymphatic endothelial cells, but its expression is also observed in endothelial cells engaged in active angiogenesis, such as tumor vessels, in endothelial tip cells of angiogenic sprouts in the developing retina or in chronic inflammatory wounds. The receptor is also found in non-endothelial cells such as osteoblasts, neuronal progenitors and macrophages – all of which may indirectly support angiogenesis. It remains unclear if tumor cells express VEGFR3. Despite this lack of clarity, inhibiting VEGFR3 activity is associated with the arrest of tumor vascularization, resulting in decreased vascular density in several tumor models.^[1]

Since the VEGF-VEGFR pathway plays a significant role in angiogenesis, and it is widely known that VEGF is highly expressed in tumor and stromal cells, especially in the inflammatory cells of human tumors, dozens of angiogenesis inhibitors are currently undergoing clinical trials.^[2] However, despite the number of compounds that has been identified for targeting the VEGF-VEGFR pathway, there is a high attrition rate. Several challenges in the development of angiogenesis inhibitors relate to their specificity, efficacy, side effects, and resistance to anti-angiogenic tumor therapy. However, the emergence of personalized medicine – based on the use of biomarkers – will likely lead to the identification of patient populations that is likely to define respondent groups.