Drug intelligence / Profile preview

zoledronic acid + paclitaxel + carboplatin + metformin

Development stage
Unknown
Lead developer
Novartis
Modality
Small Molecules
Administration
Intravenous, Oral
01

Overview

This regimen is an investigational multi-drug combination comprising zoledronic acid, paclitaxel, carboplatin, and metformin, evaluated experimentally for antineoplastic therapy, particularly in solid tumors such as non-small cell lung cancer with bone metastases and ovarian cancer. Zoledronic acid is a nitrogen-containing bisphosphonate that inhibits farnesyl pyrophosphate synthase in osteoclasts to reduce bone resorption and skeletal-related events, and has additional anti-tumor and anti-angiogenic effects. Paclitaxel is a microtubule-stabilizing taxane that promotes tubulin polymerization and prevents microtubule depolymerization, leading to mitotic arrest and apoptosis in rapidly dividing cells. Carboplatin is a platinum-based DNA-damaging agent that forms intra- and inter-strand DNA crosslinks, thereby inhibiting DNA replication and transcription and triggering apoptosis. Metformin is an oral biguanide that activates AMP-activated protein kinase (AMPK), decreases hepatic gluconeogenesis, and in oncology settings is explored for its indirect insulin-lowering and direct AMPK–mTOR pathway–modulating effects that may enhance chemosensitivity. Together, this four-drug combination is designed to provide cytotoxic chemotherapy, modulation of tumor metabolism and signaling, and protection against or treatment of bone metastases while potentially improving overall antitumor efficacy.

02

Targets

GGPPS1 (Geranylgeranyl pyrophosphate synthase)AMPK (Adenosine monophosphate–activated protein kinase)DNATUBB (Tubulin (alpha and beta subunits))FDPS (Farnesyl pyrophosphate synthase)

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