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Lenvatinib, discovered and developed by Eisai, is an orally active, selective inhibitor of receptor tyrosine kinases (RTKs) with a novel binding mode, including KDR (VEGFR-2), Flt-1 (VEGFR-1), RET, FGFR1, PDGFR-Beta and c-kit, involved in angiogenesis and tumor proliferation.
In cancer cell lines, they found that the PDGFR-Beta inhibitor sunitinib inhibited growth of cells with EMT or cancer stem cell properties that have active FOXC2.
Mani said the team believes that targeting FOXC2 pathway using cither PDGFR-beta inhibitors or other yet-to-be-known small-molecule inhibitors will be an effective therapeutic strategy for inhibiting EMT and consequently reducing EMT/cancer stem cell-associated metastasis, relapse and therapy resistance.
Mani said the team believes that targeting FOXC2 pathway using either PDGFR-beta inhibitors or other yet-to-be-known small-molecule inhibitors will be an effective therapeutic strategy for inhibiting EMT and consequently reducing EMT/cancer stem cell-associated metastasis, relapse and therapy resistance.
Aguzzi and colleagues reasoned that this may be due to mural cells losing expression of PDGFR-Beta during their maturation into FDCs.
Reporter" mice were generated whose FDCs would be stained by a blue marker if they had expressed PDGFR-Beta at any point in their life, even if PDGFR-Beta expression was suppressed at the time of analysis.
A preliminary study on the changes of expression of PDGF-beta, PDGFR-beta, TGF-beta 1, TGFR, bFGF and its relationship with the wound age in wound healing.
In pre-clinical testing, XL999 inhibited KDR, FGFR1, PDGFR-beta and FLT3 with high potency.
According to the companies, the preclinical data suggests that combining PDGFR-beta blockade with vascular endothelial growth factor (VEGF) blockade by EYLEA can provide advantages over inhibiting VEGF alone in the treatment of this devastating eye disease.
Aarif Khakoo and colleagues have now identified a role for PDGFR-beta in mouse heart muscle cells that might help explain why inhibitors of PDGFR signaling can cause heart failure.
These molecules are able to bind to two validated tumour targets: HER-2, which is present on aggressive breast tumours, and PDGFR-beta, which plays a significant role in angiogenesis associated with solid tumour growth and development.
We look forward to building on our relationship in ophthalmology with this potential next generation product candidate which will combine Regeneron s PDGFR-beta antibody and Eyelea in a single intravitreal injection.
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- PDGF subunit B
- PDGF, B chain
- PDGFA-Associated Protein 1
- PDGFRA/BCR fusion
- PDH complex
- PDH complex