Cridanimod (Virexxa) is a small-molecule immunomodulator and interferon inducer, which, in preliminary studies, has been shown to increase progesterone receptor expression in endometrial tissue. Restoration of progesterone receptor expression may re-sensitize endometrial tumor tissue to progestin therapy in previously unresponsive tumors. Cridanimod was originally developed by Polysan and Pharmsynthez and licensed to Xenetic Biosciences. Virexxa is currently being studied in an ongoing Phase 2 multi-national study in conjunction with progestin therapy for the treatment of endometrial cancer in women with the recurrent or persistent disease who have failed progestin monotherapy.

Buformin (1-butylbiguanide) is an oral antidiabetic drug of the biguanide class. AMPK activator. AMPK is a potential therapeutic target in the prevention and the treatment of type 2 diabetes and insulin resistance. Major classes of antidiabetic drugs have been reported to activate AMPK. Buformin exerts its anti-tumorigenic activity via activation of AMPK and inhibition of the mTOR signaling pathways in endometrial cancer cells. Toxicity: guinea pig LD50 subcutaneous 18 mg/kg; mouse LD50 intraperitoneal 140 mg/kg and 300 mg/kg oral. Buformin was withdrawn from the market in many countries due to an elevated risk of causing lactic acidosis.

Gestonorone is a progesterone analogue indicated for the treatment of benign prostatic hyperplasia and endometrial cancer. The drug is approved in many countries and used under the names Primostat and Depostat.