FIP1L1 Inhibitors
FIP1L1 inhibitors are a category of chemical compounds designed to specifically target and impede the activity of the FIP1L1 protein. The FIP1L1 protein is a fusion protein that often results from a chromosomal translocation that brings together parts of the FIP1-like 1 (FIP1L1) gene and the platelet-derived growth factor receptor alpha (PDGFRA) gene. This fusion leads to the constitutive activation of the tyrosine kinase activity inherent in the PDGFRA component, driving aberrant cell proliferation and survival signals. FIP1L1 inhibitors interact with the ATP-binding site of this chimeric tyrosine kinase, thereby inhibiting its enzymatic activity. By doing so, they effectively halt the phosphorylation cascade that would normally result from the unregulated activity of the fusion protein, thereby disrupting the proliferation signal. The specificity of FIP1L1 inhibitors lies in their ability to fit into the unique conformation of the fusion protein's kinase domain, which distinguishes them from inhibitors targeting the normal PDGFRA protein.
These inhibitors not only arrest the phosphorylation activity but also affect the downstream signaling pathways that are crucial for cell cycle progression and survival, such as the STAT, RAS/MAPK, and PI3K/AKT pathways. By interfering with these pathways, FIP1L1 inhibitors induce apoptosis and reduce the proliferation of cells expressing the FIP1L1-PDGFRA fusion protein. The action of these inhibitors is highly specific to the aberrant signaling caused by the fusion protein and does not generally impact the normal cellular processes governed by the native PDGFRA. This specificity is critical to their mode of action, as it allows for a targeted approach to inhibit the pathological overactivation without broadly affecting the PDGFRA-related signaling in healthy cells. The design of FIP1L1 inhibitors is grounded in a profound understanding of the molecular structure and activation mechanisms of the fusion kinase, which ensures that the binding of these compounds is both effective and selective.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Imatinib | 152459-95-5 | sc-267106 sc-267106A sc-267106B | 10 mg 100 mg 1 g | $25.00 $117.00 $209.00 | 27 | |
Imatinib is a tyrosine kinase inhibitor that specifically targets the BCR-ABL fusion protein, which is a consequence of the t(9;22) chromosomal translocation. This translocation often involves the FIP1L1 gene, leading to the formation of the FIP1L1-PDGFRA fusion kinase in cases like chronic eosinophilic leukemia. Inhibition of this kinase by Imatinib leads to decreased FIP1L1 activity. | ||||||
PKC-412 | 120685-11-2 | sc-200691 sc-200691A | 1 mg 5 mg | $51.00 $112.00 | 10 | |
Midostaurin is a multi-targeted kinase inhibitor that blocks the activity of protein kinases such as FLT3 and KIT, which are involved in cell growth and survival pathways. By inhibiting these kinases, Midostaurin can suppress the downstream effects on the signaling pathways that may indirectly influence FIP1L1 activity, especially if the FIP1L1 gene is part of a fusion protein with one of these kinases. | ||||||
Sorafenib | 284461-73-0 | sc-220125 sc-220125A sc-220125B | 5 mg 50 mg 500 mg | $56.00 $260.00 $416.00 | 129 | |
Sorafenib is a RAF inhibitor that also inhibits multiple other tyrosine protein kinases, such as VEGFR and PDGFR. Given that FIP1L1 can be involved in fusion proteins with tyrosine kinase activity, Sorafenib may indirectly decrease FIP1L1-related signaling by inhibiting the kinase activity of its fusion partners. | ||||||
Dasatinib | 302962-49-8 | sc-358114 sc-358114A | 25 mg 1 g | $47.00 $145.00 | 51 | |
Dasatinib is a BCR-ABL kinase inhibitor more potent than Imatinib. It also inhibits the SRC family of kinases. As such, Dasatinib is capable of inhibiting signaling pathways involving tyrosine kinases, potentially including those in which FIP1L1 fusion proteins are involved, thereby reducing FIP1L1 kinase activity. | ||||||
AP 24534 | 943319-70-8 | sc-362710 sc-362710A | 10 mg 50 mg | $172.00 $964.00 | 2 | |
Ponatinib is a third-generation tyrosine kinase inhibitor designed to inhibit the BCR-ABL tyrosine kinase, including its more resistant forms. It can also inhibit other kinases like FGFR, which may play a role in signaling pathways involving FIP1L1, particularly if FIP1L1 is part of a fusion kinase protein, leading to a reduction in FIP1L1 activity. | ||||||
Nilotinib | 641571-10-0 | sc-202245 sc-202245A | 10 mg 25 mg | $205.00 $405.00 | 9 | |
Nilotinib is another selective BCR-ABL tyrosine kinase inhibitor, which has shown to be effective against certain types of leukemia where FIP1L1-PDGFRA fusion proteins are involved. By targeting the tyrosine kinase activity, Nilotinib can reduce the abnormal signaling associated with this fusion protein, thereby leading to decreased FIP1L1 activity. | ||||||
Lestaurtinib | 111358-88-4 | sc-218657 sc-218657A sc-218657B | 1 mg 5 mg 10 mg | $270.00 $320.00 $600.00 | 3 | |
Lestaurtinib is a tyrosine kinase inhibitor with specificity for FLT3. It has the potential to inhibit the signaling pathways connected to FIP1L1, particularly in forms of leukemia where FIP1L1 is part of a fusion protein with other tyrosine kinases. This inhibition can lead to reduced activity of FIP1L1 fusion proteins. | ||||||
Masitinib | 790299-79-5 | sc-211777 | 10 mg | $180.00 | ||
Masitinib is a tyrosine kinase inhibitor that targets c-KIT, PDGFR, and FGFR, among others. It can be posited that by inhibiting these kinases, Masitinib could interfere with the signaling pathways that involve FIP1L1 fusion proteins, thus potentially leading to a decrease in FIP1L1 activity. | ||||||
Pazopanib | 444731-52-6 | sc-396318 sc-396318A | 25 mg 50 mg | $127.00 $178.00 | 2 | |
Pazopanib is a multi-targeted receptor tyrosine kinase inhibitor that affects VEGFR, PDGFR, and KIT. In scenarios where FIP1L1 forms fusion proteins with these or related kinases, Pazopanib might indirectly decrease the activity of FIP1L1 by inhibiting the kinase activity of its fusion partners. | ||||||