Table 1.
Compounds with potentially radiosensitizing properties.
| Compound | Mode of action | Specificities | References |
|---|---|---|---|
| HIF-1 signaling | |||
| Deguelin, SH-14 | Akt inhibition, downregulation HIF-1α, reduced hexokinase expression | Potential CI inhibitor- Development of Parkinson’s disease-like syndrome in rat; SH-14 is a deguelin derivative | (20, 21) |
| Vandetanib | Inhibition, EGFR, HIF-1α signaling interference | FDA-approved for medullary thyroid cancer therapy | (22–27) |
| Berberine | Downregulation HIF-1α & VEGF | (28–31) | |
| Rg3 | Inhibition NF-κB, decreased expression HIF-1α & VEGF | (32, 33) | |
| Cellular metabolism | |||
| Glucose metabolism | |||
| BAY-876 | GLUT1 inhibition | In vitro cisplatin sensitizer, radiosensitizing effects unclear | (34, 35) |
| WZB117 | GLUT1 inhibition | (36, 37) | |
| 2-DG, WP1122 | Glucose analogue, hexokinase inhibition, radiosensitizing mechanism unclear | Tumor staging and metabolism profiling via PET-imaging using 2-DG coupled to positron-emitting isotopes; WP1122 is a 2-DG analogue | (38–41) |
| Lonidamine | Glycolysis inhibition, TCA cycle & CII interference | Negative results in clinics | (42–44) |
| Devimistat | Deregulation TCA cycle enzymes, ROS induction | In phase 2/3 trials combined with chemotherapeutics; No studies about combination with radiotherapy | (45, 46) |
| FH535 and Y3 | Distortion mitochondrial membrane potential, apoptosis inducer | Y3 is an FH535-analogue | (47, 48) |
| Ivosidenib | IDH1mut inhibition | FDA-approved for acute/refractory AML | (49) |
| Enasidenib | IDH2mut inhibition | FDA-approved for acute/refractory AML | (50, 51) |
| Vorasidenib | IDH1/2mut inhibition | Clinical trials | (52, 53) |
| BAY-1436032 | IDH1mut inhibition | Clinical trials | (54, 55) |
| Complex I | |||
| Metformin | Inhibition CI, oxygen accumulation and subsequent HIF-1-α destabilization, reduces PI3K/Akt signaling | FDA-approved for anti-diabetes therapy | (56, 57) |
| Phenformin | CI inhibition | Redrawn, induces lactic acidosis in diabetes patients; Clinical trials phase I | (58, 59) |
| Papaverine | CI inhibition and PDE10A | FDA-approved as anti-vasospasm therapeutic; In vivo radiosensitization | (60, 61) |
| SMV-32 | CI inhibition | Papaverine derivative; In vivo radiosensitizing; Clinical trials phase I | (61) |
| BAY 87 2243 | In vivo radiosensitizing; Clinical trials status unclear | NCT01297530 | |
| IACS-010759 | Radiosensitizing effect unclear |
NCT03291938 NCT02882321 |
|
| Complex III | |||
| Atovaquone | Complex III inhibition | FDA-approved for anti-malaria therapy; Clinical trials phase I | (62, 63) |
| Pyrazinib | OCR/ECAR reduction | Precise target unknown | (64) |
| Other pathways | |||
| ADI-PEG | Arginine depletion | Arginine deiminase and polyethylene glycol chimera- Clinical trials in combination with chemotherapy | (65–67) |
| Orlistat | FASN inhibition | FDA-approved for obesity-management | (68) |
| Fenofibrate | Activates PPARα, metabolic reprogramming via CPT1, AMPK and HK2 Prevention of HIF-1 stabilization | FDA-approved for hypercholesterolemia, mixed dyslipidemia and severe hypertriglyceridemia | (69–71) |
| Redox signaling | |||
| Telaglenastat | GLS inhibition | Improved bioavailability, chemotherapeutic and immunotherapeutic outcomesFDA-approved for advanced renal cell carcinomas | (72–75) |
| Auranofin | TrX-reductase inhibition | FDA-approved for arthritis therapy | (41, 76) |
The compounds are grouped according to their intracellular effects.