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E7449 + carboplatin + paclitaxel
- Development stage
- Phase 2
- Lead developer
- Allarity Therapeutics
- Modality
- Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, MicroRNA (miRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Antisense Oligonucleotides (ASOs) → Long RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics, Small Molecules
- Administration
- Oral, Intravenous
01
Overview
E7449 (also known as 2X-121 or Stenoparib) is an orally bioavailable, brain penetrable small molecule that acts as a dual inhibitor of poly(ADP-ribose) polymerase (PARP) 1/2 and tankyrase (PARP5a/5b, also known as TNKS1/2). By inhibiting PARP1/2, E7449 impairs DNA repair via the base excision repair pathway and traps PARP on damaged DNA, leading to increased cytotoxicity in tumor cells—especially those deficient in homologous recombination repair such as BRCA-mutant tumors. Inhibition of tankyrase by E7449 disrupts Wnt/β-catenin signaling through stabilization of axin and TNKS proteins, resulting in β-catenin destabilization and altered expression of Wnt target genes. This dual mechanism may broaden its therapeutic potential beyond traditional PARP inhibitors. Preclinical studies show that E7449 potentiates the activity of chemotherapeutic agents like carboplatin and paclitaxel. The combination is under early clinical investigation for advanced solid tumors[1][6][3][4].
- Other names
- MGI25036MGI-25036MGI 25036Parp inhibitor 2x-121
02
Targets
DNAPARP1 (Poly (adp-ribose) polymerase 1)PARP2 (Poly (adp-ribose) polymerase 2)TNKS (Poly(ADP-ribose) Polymerase 5a)TNKS2 (Tankyrase 2)TUBB (Tubulin (alpha and beta subunits))Pol II (RNA polymerase II elongation factors)
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