ONX 0801 (BGC 945) trisodium is a targeted thymidylate synthase (TS) inhibitor specifically designed to act against tumors overexpressing the [α-folate receptor].

ONX 0801 (BGC 945) is designed to minimize toxicity and enhance specificity for cancer cells overexpressing the α-FR, with IC 50 values of 6.6 μM in A431, 1.1 nM in A431-FBP, 3.3 nM in KB, 90 nM in IGROV-1, and 0.32 μM in JEG-3 cells.

BGC 945, administered at a dosage of 100 mg/kg either through intraperitoneal (ip) or intravenous (iv) injection, was found to exhibit a prolonged half-life of 28 hours within tumor tissues, indicating enhanced persistence compared to other tissues. Notably, the compound, when administered daily for 16 days at the same dosage, did not result in any observable body weight loss, evident toxicity to major organs, or alterations in renal function. It also significantly increased tumor deoxyuridine (dUrd) levels by 5-20-fold within 4-72 hours post-administration without affecting plasma levels, suggesting effective tumor targeting. In an animal model, mice were placed on a folate-free diet for five days before tumor transplantation and treatment initiation. Pharmacokinetic analysis revealed that after intraperitoneal injection, BGC 945 was efficiently absorbed, yielding a 50% higher area under the curve (AUC) for plasma concentration compared to intravenous routes. The AUC was also increased in the spleen, kidney, and liver via intraperitoneal administration, with tumor AUC remaining consistent across both administration routes.