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O6-benzylguanine
O6-benzylguanine is an alkyltransferase inhibitor that depletes the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT), sensitizing cancer cells to alkylating chemotherapy agents.
O6-benzylguanine is an alkyltransferase inhibitor that depletes the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT), sensitizing cancer cells to alkylating chemotherapy agents. Used for Glioblastoma (in combination with alkylating chemotherapy), Melanoma (in combination with alkylating chemotherapy).
At a glance
| Generic name | O6-benzylguanine |
|---|---|
| Also known as | 6-O-Benzylguanine, O(6)-Benzylguanine, 06-BG, BG, O6-BG |
| Sponsor | Case Comprehensive Cancer Center |
| Drug class | DNA repair inhibitor / Alkyltransferase inhibitor |
| Target | O6-alkylguanine-DNA alkyltransferase (AGT) |
| Modality | Small molecule |
| Therapeutic area | Oncology |
| Phase | Phase 3 |
Mechanism of action
O6-benzylguanine acts as a suicide substrate for AGT, a DNA repair enzyme that normally protects cells from the cytotoxic effects of alkylating agents like temozolomide and carmustine. By depleting AGT levels, the drug prevents cancer cells from repairing alkylation-induced DNA damage, thereby enhancing the efficacy of concurrent chemotherapy. This mechanism is particularly relevant in tumors with high AGT expression.
Approved indications
- Glioblastoma (in combination with alkylating chemotherapy)
- Melanoma (in combination with alkylating chemotherapy)
Common side effects
- Myelosuppression
- Nausea and vomiting
- Fatigue
- Hepatotoxicity
Key clinical trials
- hSTAR GBM (Hematopoetic Stem Cell (HPC) Rescue for GBM) (PHASE2)
- BG & TMZ Therapy of Glioblastoma Multiforme (PHASE1)
- O6-Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cell in Treating Patients With Malignant Gliomas (PHASE1, PHASE2)
- O6-Benzylguanine and Temozolomide in Treating Young Patients With Recurrent or Progressive Gliomas or Brain Stem Tumors (PHASE2)
- HIV-Resistant Gene Modified Stem Cells and Chemotherapy in Treating Patients With Lymphoma With HIV Infection (PHASE1)
- O(6)-Benzylguanine in Treating Patients With Malignant Glioma (PHASE1)
- O6-Benzylguanine and Topical Carmustine in Treating Patients With Early-Stage IA-IIA Cutaneous T-Cell Lymphoma (PHASE1, PHASE2)
- O(6)-Benzylguanine and Temozolomide in Treating Patients With Glioblastoma Multiforme That Did Not Respond to Previous Temozolomide and Radiation Therapy (PHASE2)
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
Competitive intelligence
For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:
- O6-benzylguanine CI brief — competitive landscape report
- O6-benzylguanine updates RSS · CI watch RSS
- Case Comprehensive Cancer Center portfolio CI