Milciclib (PHA-848125) is a potent ATP-competitive cyclin A/CDK2 inhibitor with potential anti-neoplastic, or anti-cancer, activity.

How does milciclib work?

The period it takes for a cell to divide and create a new, identical one is the cell’s life cycle. During this process, cells evolve through several stages to divide at the final step. Each stage is highly regulated, so that the cell proceeds to the next step only when all the machinery it requires is ready.

In the first part of the cycle, the cell grows bigger so it can divide and separate in the next stages. A group of proteins called cyclin-dependent kinases (CDKs) stop that growth so the next stages can begin.

Milciclib works by inhibiting the specific CDKs that initiate the division process. In cancer cells, which divide abnormally, the cell’s life cycle would be interrupted at the growth stage and cancer cells would not generate new ones.

Using milciclib in combination with a chemotherapeutic drug can help control tumor size and improve the removal of damaged cells.

Studies with milciclib

A Phase 1, open-label, multicenter clinical trial (NCT01300468) to evaluate the safety of milciclib in combination with the chemotherapeutic drug gemcitabine enrolled 16 patients with advanced metastatic tumors that resisted existing therapies.

The treatment regimen consisted of oral milciclib once a day for seven consecutive days, every two weeks, and intravenous (into the blood stream) administration of gemcitabine once a week, for four weeks.

This combination treatment regimen showed positive clinical responses in 36% of patients, including in patients resistant to gemcitabine treatment. One patient with non-small cell lung carcinoma (NSCLC) showed partial response, and four others (one each with thyroid, prostatic, pancreatic carcinoma and peritoneal mesothelioma) showed long-term disease stabilization for up to 14 months.

Tiziana Life Sciences announced in a press release that the results of this clinical trial were published in the peer-reviewed journal Cancer Chemotherapy and Pharmacology in April.

The company will further evaluate milciclib in a Phase 2a clinical trial (NCT03109886) in patients with drug-resistant hepatocellular carcinoma (HCC) that is expected to begin shortly. It also has two ongoing Phase 2 clinical trials to test the effect of Milciclib in patients with thymic carcinoma (NCT01011439) and malignant thymoma (NCT01301391).

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