Table 3.
FRβ therapeutic targeting in rheumatoid arthritis
| Category | Remarks | Reference |
|---|---|---|
| Antifolates | ||
| MTX | DHFR inhibitor, low FR affinity, high RFC/PCFT affinity | [102] |
| CH-1504 | DHFR inhibitor, low FR affinity, high RFC affinity | [140] |
| EC0746 | Aminopterin-folate conjugate DHFR inhibitor, activity in RA mouse model | [141] |
| EC0746 | Aminopterin-folate conjugate DHFR inhibitor, activity in animal uveitis and encephalomyelitis model | [105] |
| BGC945 | TS inhibitor, FRα/β specific | [81, 142] |
| ALIMTA/pemetrexed | TS inhibitor, moderate FR affinity, high RFC/PCFT affinity | [143] |
| LY309887 | GARTFase inhibitor, high FR and RFC affinity, activity in mouse RA model | [144] |
| LY329201 and LY309886 | GARTFase inhibitors, in vitro activity, and activity in rat RA model | [145] |
| Divers compounds | GARTFase inhibitors, FRβ selective, in vitro activity | [146] |
| Immunotoxins | ||
| Anti-FRβ-PE38 | Recombinant immunotoxin dsFv anti-FRβ-Pseudomonas endotoxin A (PE38). Reduction RA synovial macrophages and fibroblasts | [147–149] |
| Anti-FRβ-PE38 | Targeting FRβ-positive tumor-associated macrophages in mouse glioma | [150] |
| Anti-FRβ-PE38 | Targeting FRβ-positive macrophages mouse atherosclerotic lesions | [151] |
| Folate-conjugated nanoparticles | ||
| G5 dendrimer MTX | Targeting mouse primary FRβ macrophages | [152] |
| Liposomes + MTX | Activity to FRβ-positive macrophages in mouse collagen-induced arthritis | [153] |
| Dextran-MTX | Activity to FRβ-positive macrophages in mouse collagen-induced arthritis | [154] |
| Liposomes + anti-inflammatory drugs | Targeting activated macrophages in inflammatory diseases | [155] |
| NFkB decoy | Delivery to murine macrophages | [156] |
| G5 dendrimers MTX | Targeting FRβ-positive tumor-associated macrophages | [157] |
| Liposomes + zoledronate | Targeting FRβ-positive tumor-associated macrophages | [158] |
| HSA-nanodrug | Targeting FRβ-positive AML cells | [159] |
| Liposomes + Dox | Targeting FRβ-positive AML cells | [160] |
| Folate drug conjugates | ||
| FA-Everolimus (EC0565) | Targeting FRβ-positive rat macrophages | [161] |
| FDG-FA | Targeting FRα-positive tumors and FRβ-positive macrophages | [162] |
| Gene delivery (miRNA, siRNA) | ||
| FA-liposomes +MCL1-siRNA | Delivery to activated macrophages | [163] |
| FA-micelles/hydrogels | Gene delivery to activated macrophages | [164] |
| FolamiRs | FA-conjugated microRNAs for delivery to FR-positive cells | [165] |
| CAR T cells | ||
| High affinity FRβ-specific CAR T cells | For eradication FRβ-positive AML cells | [166, 167] |