VEGFR Inhibitors

Övrigt Protein Tyrosine Kinase Inhibitorer

Isoformselektiva produkter

• Utvalda inhibitorer
• Inhibitorer (105)
• Kemikalier (2)

Kat.nr.	Produktnamn	Information	Citeringar av produktanvändning	Produktvalideringar
S2842	SAR131675	SAR131675 är en VEGFR3-hämmare med IC50/Ki på 23 nM/12 nM i cellfria analyser, cirka 50- och 10-faldigt mer selektiv för VEGFR3 än VEGFR1/2, liten aktivitet mot Akt1, CDKs, PLK1, EGFR, IGF-1R, c-Met, Flt2 etc.	Cell Death Discov, 2025, 11(1):320 Zool Res, 2025, 46(6):1317-1325 Cell Signal, 2025, 130:111675
S1010	BIBF 1120 (Nintedanib)	Nintedanib är en potent trippel angiokinashämmare för VEGFR1/2/3, FGFR1/2/3 och PDGFRα/β med IC50 på 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM och 59 nM/65 nM i cellfria analyser. Fas 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)	En potent VEGFR2-hämmare med IC50 på 0,035 nM, Cabozantinib (XL184) hämmar även c-Met, Ret, Kit, Flt-1/3/4, Tie2 och AXL med IC50 på 1,3 nM, 4 nM, 4,6 nM, 12 nM/11,3 nM/6 nM, 14,3 nM respektive 7 nM i cellfria analyser. Den inducerar PUMA-beroende apoptos i koloncancerceller via AKT/GSK-3β/NF-κB-signalvägen.	Cell Reports Medicine, September 20, 2022, 100659 Redox Biology, October 21, 2023, 102945 Hepatology Communications, November 8, 2023, e0313
S1164	E7080 (Lenvatinib)	Lenvatinib är en multi-målinriktad hämmare, främst för VEGFR2(KDR)/VEGFR3(Flt-4) med IC50 på 4 nM/5.2 nM, mindre potent mot VEGFR1/Flt-1, ~10 gånger mer selektiv för VEGFR2/3 mot FGFR1, PDGFRα/β i cellfria analyser. Lenvatinib (E7080) hämmar också FGFR1-4, PDGFR, Kit (c-Kit), RET (c-RET), och visar potenta antitumöraktiviteter. Fas 3.	Signal Transduct Target Ther, 2026, 11(1)138 Int J Biol Sci, 2026, 22(7):3617-3634 Cell Death Dis, 2026, 17(1)360
S1005	Axitinib (AG-013736)	Axitinib är en multi-target hämmare av VEGFR1, VEGFR2, VEGFR3, PDGFRβ och c-Kit med IC50 på 0,1 nM, 0,2 nM, 0,1-0,3 nM, 1,6 nM respektive 1,7 nM i endotelceller från grisaorta.	Pharmacol Res, 2026, 225:108112 Development, 2026, 153(16)dev205344 J Exp Zool B Mol Dev Evol, 2026, 346(1):7-19
S7667	SU 5402	SU5402 är en potent multi-targeterad receptor-tyrosinkinas-hämmare med IC50 på 20 nM, 30 nM och 510 nM för VEGFR2, FGFR1 respektive PDGFRβ.	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 är en potent och selektiv oralt biotillgänglig, pan fibroblast growth factor receptor (FGFR)-hämmare med potentiell antineoplastisk aktivitet. Denna förening binder även till RET (c-RET), CSF-1R, PDGFR-α/PDGFR-β, FLT4, Kit (c-Kit) och VEGFR-2 och inducerar cellulär apoptosis.	Cell Death Dis, 2025, 16(1):868 Commun Biol, 2025, 8(1):394 Int J Mol Sci, 2025, 26(8)3525
S7397	Sorafenib (BAY 43-9006)	Sorafenib är en multikinashämmare av Raf-1 och B-Raf med IC50 på 6 nM respektive 22 nM i cellfria analyser. Sorafenib hämmar VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 och c-KIT med IC50 på 90 nM, 20 nM, 57 nM, 59 nM respektive 68 nM. Sorafenib inducerar autophagy och apoptosis och aktiverar ferroptosis med antitumöraktivitet.	Signal Transduct Target Ther, 2026, 11(1)79 Int J Surg, 2026, 10.1097/JS9.0000000000004913 Acta Pharmacol Sin, 2026, 10.1038/s41401-026-01791-z
S1029	CC-5013 (Lenalidomide)	Lenalidomid är en TNF-α sekretionshämmare med IC50 på 13 nM i PBMC:er. Lenalidomid (CC-5013) är en ligand till ubiquitin E3-ligas cereblon (CRBN), och det orsakar selektiv ubiquitinering och nedbrytning av två lymfoida transkriptionsfaktorer, IKZF1 och IKZF3, av CRBN-CRL4 ubiquitinligaset. Lenalidomid främjar klyvt Caspase-3 uttryck och hämmar VEGF uttryck och inducerar apoptos.	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 är en ny, potent multi-target-hämmare av Abl, PDGFRα, VEGFR2, FGFR1 och Src med ett IC50 på 0,37 nM, 1,1 nM, 1,5 nM, 2,2 nM respektive 5,4 nM i cellfria analyser. Ponatinib (AP24534) hämmar Autophagy.	Acta Pharmacol Sin, 2026, 10.1038/s41401-026-01791-z J Cell Mol Med, 2026, 30(4):e71053 Cancers (Basel), 2026, 18(7)1082
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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.