Lomeguatrib
Pronunciation: pronunciation varies by local usage.
- Generic name
- lomeguatrib
- Drug class
- Investigational O6-methylguanine-DNA methyltransferase (MGMT) inhibitor; chemosensitizer
- Form
- No marketed dosage form or regulatory prescribing label was identified; trial dosing used oral daily dosing schedules
- Route
- Oral, in the clinical trials reviewed
- Legal status
- Investigational compound; no FDA or other regulatory approval identified. Industry drug-tracking sources describe its highest reported global development status as discontinued.
Availability and supply rules vary by country
Trade names by country:
Australia: · Full directory
What lomeguatrib is and how it works
Lomeguatrib is an investigational small-molecule pseudosubstrate inhibitor of O6-methylguanine-DNA methyltransferase (MGMT), a DNA-repair enzyme that removes methyl and alkyl adducts from the O6 position of guanine. By inactivating MGMT, lomeguatrib was designed to deplete tumor cells' capacity to repair DNA damage caused by alkylating chemotherapy agents such as temozolomide and dacarbazine, intended to increase ("chemosensitize") the cytotoxic effect of those chemotherapy drugs.
Lomeguatrib is not an FDA-approved medicine and no marketed product, approved indication, approved dose, or regulatory prescribing label was identified. It was studied only in early-phase (Phase I/II) oncology trials as a chemosensitizer given together with alkylating chemotherapy in melanoma and other solid tumors. Industry drug-tracking sources describe its highest reported research-and-development phase as discontinued, without progressing to registration or approval. This page describes lomeguatrib as an investigational, non-approved compound with only early-phase trial data available, not as a marketed medicine with standard prescribing information.
Mechanism of action: how lomeguatrib works
Lomeguatrib is a pseudosubstrate inhibitor of O6-methylguanine-DNA methyltransferase (MGMT), designed via O6-position modification of the guanine scaffold to inactivate MGMT while aiming to avoid the severe myelosuppression associated with an earlier-generation MGMT inhibitor, O6-benzylguanine. This is described in the secondary literature reviewed as a design intent, not a proven clinical safety advantage, since dose-limiting hematologic toxicity was still reported in the lomeguatrib plus temozolomide combination trials. Preclinical (animal) studies observed MGMT depletion in normal tissues and in subcutaneous melanoma tumor xenografts for up to 24 hours after a single 20 mg/kg dose of lomeguatrib.
What lomeguatrib is used for
No approved use
No approved indication was identified. Lomeguatrib was studied in Phase I and Phase I/II trials, combined with alkylating chemotherapy (temozolomide or dacarbazine), as a chemosensitizer in advanced melanoma and other solid tumors. Separately, laboratory (in vitro) research explored MGMT inhibition in glioblastoma and multiple myeloma cell lines as a strategy to increase sensitivity to alkylating therapy or radiotherapy; these are preclinical laboratory findings only and are not evidence of clinical benefit in those indications.
Before taking lomeguatrib
Do not take / not appropriate for
- No regulatory contraindications can be stated because no FDA-approved prescribing label or marketed product was identified. ()
Tell your clinician about
- Lomeguatrib is investigational and no approved patient-use instructions or regulatory safety label were identified.
- If considering participation in any research study involving this compound, discuss the study-specific eligibility, safety procedures, potential risks, and alternatives with the study team and an appropriate clinician.
How to take lomeguatrib
- There is no approved dose, schedule, or marketed product for lomeguatrib.
- In the Phase I trial reviewed, lomeguatrib 40 mg/day was combined with temozolomide 125 mg/m2/day for 5 consecutive days as tolerated in that study population. A related dose-schedule study identified lomeguatrib for 10 days with temozolomide 75 mg/m2 as an extended dosing schedule tested in that trial.
- These are strictly trial doses from specific small studies, not an approved or recommended dose, and must not be treated as prescribing information or as a self-directed treatment plan.
- Any administration in a research setting must follow the authorised study protocol and direction of the research team.
Procedures and treatment changes
Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician.
Missed dose
No approved missed-dose guidance exists because lomeguatrib is not a marketed medicine. Participants in a clinical study should contact the study team for protocol-specific direction.
Overdose
No approved overdose guidance or regulatory label was identified. If an investigational product administration error or unexpected symptoms occur in a research setting, contact the study team or seek urgent medical assessment as appropriate.
Side effects
There is no approved-drug safety label for lomeguatrib. Reported findings below are from Phase I and Phase I/II development, combined with alkylating chemotherapy, and do not establish the safety profile of an approved medicine used alone.
Hematologic toxicity (myelosuppression)
What to notice: In the lomeguatrib plus temozolomide trials reviewed, hematologic toxicity (myelosuppression) was reported as the dose-limiting toxicity. A detailed symptom-level adverse-event table was not extracted from the sources reviewed in this session.
What to do: In a clinical study, report any unusual bruising, bleeding, infection, fever, or fatigue to the study team promptly so they can assess it under the study protocol.
Other adverse events (not itemised in the sources reviewed)
What to notice: Full or precise adverse-event tables beyond the noted dose-limiting hematologic toxicity were not extracted from the sources reviewed in this session; primary full-text journal articles were access-restricted.
What to do: In a clinical study, report any new or concerning symptom to the study team so it can be assessed under the study protocol.
Unexpected or concerning symptoms during research participation
What to notice: A specific serious-adverse-effect profile, warning list, and regulatory safety guidance were not established in the research reviewed, beyond the noted dose-limiting hematologic toxicity in combination trials.
What to do: Contact the research team or an appropriate clinician promptly for assessment.
Serious warnings
Dose-limiting hematologic toxicity (myelosuppression) — serious, reported in trials
Symptoms: Myelosuppression was the reported dose-limiting toxicity in the lomeguatrib plus temozolomide trials reviewed; a specific symptom checklist was not established in the sources reviewed in this session.
Action: Research participants experiencing unusual bruising, bleeding, infection, fever, or severe fatigue should contact the study team promptly, or seek urgent medical assessment for any severe or emergency symptom.
Regulatory safety information unavailable outside trial context —
Symptoms: No approved prescribing label or confirmed regulatory serious-warning list was identified, because lomeguatrib has never been approved for marketing.
Action: Urgent symptoms require appropriate urgent or emergency medical assessment. Research participants should also notify the study team according to the study protocol.
Interactions
| Medicine or test | Effect | Action |
|---|---|---|
| Alkylating chemotherapy (temozolomide, dacarbazine) | Lomeguatrib was specifically studied in combination with alkylating chemotherapy agents (temozolomide, dacarbazine) as a chemosensitizer, intended to increase their cytotoxic effect by inactivating the DNA-repair enzyme MGMT. Combination-trial dosing carried dose-limiting hematologic toxicity in the studies reviewed. | Any combination use is strictly within a clinical-trial protocol; research participants should provide the study team with a complete list of medicines, supplements, and treatments for protocol-specific review. |
| Other medicines, supplements, and treatments | Interaction information from an approved regulatory label was not available because lomeguatrib is investigational and no marketed prescribing label was identified. | Research participants should provide the study team with a complete list of medicines, supplements, and treatments for protocol-specific review. |
Pregnancy, breastfeeding, kidney/liver function, age
Pregnancy and breastfeeding
No approved-label guidance or population-specific information was established in the research reviewed. Any research-study eligibility decision requires protocol-specific assessment by the study team.
Children and adolescents
No approved paediatric use, dose, or regulatory guidance was identified. The trials reviewed were conducted in adult patients with advanced solid tumors.
Renal or hepatic impairment
Renal and hepatic impairment guidance was not established in the research reviewed.
Monitoring
Before starting
- No approved treatment-starting assessment exists because lomeguatrib is not a marketed medicine.
- For any clinical trial, eligibility and baseline assessment (including blood counts, given the reported hematologic dose-limiting toxicity) must follow the specific research protocol and study team's procedures.
During treatment
- No approved monitoring schedule or regulatory safety-monitoring requirements were identified outside a clinical-trial protocol.
- Clinical-trial monitoring, including monitoring for myelosuppression, must follow the specific research protocol and study team's procedures.
Storage
No marketed product storage instructions were identified. Storage of any investigational supply must follow the applicable clinical-study protocol and study-site instructions.
Investigational-compound information
Clinician-facing context only. Lomeguatrib is investigational, with no identified FDA-approved prescribing label, marketed product, approved indication, or approved dose. This page is not a substitute for a clinical-trial protocol or study-investigator guidance.
All regions
Indication: No approved indication identified
Dose summary: No approved dose or dosing schedule exists. A Phase I trial reviewed used lomeguatrib 40 mg/day with temozolomide 125 mg/m2/day for 5 consecutive days; a related dose-schedule study tested lomeguatrib for 10 days with temozolomide 75 mg/m2 as an extended schedule, with myelosuppression as the dose-limiting toxicity and roughly a 6.25% overall response rate reported in that specific small trial population. These research doses are not prescribing guidance.
Renal context: Renal and hepatic impairment dosing information was not established in the research reviewed.
Hepatic guidance
Hepatic impairment information was not established in the research reviewed.
Overdose note
No approved overdose-management guidance was identified. Investigational-product errors require assessment under the relevant study protocol and by the study team or appropriate medical service.
Frequently asked questions
Is lomeguatrib an approved cancer treatment?
No. The research reviewed found no FDA approval, marketed product, approved indication, approved dose, or regulatory prescribing label for lomeguatrib. Industry drug-tracking sources describe its highest reported development status as discontinued.
How does lomeguatrib work?
Lomeguatrib inactivates MGMT, a DNA-repair enzyme, which reduces tumor cells' ability to repair damage from alkylating chemotherapy drugs such as temozolomide and dacarbazine. It was studied as a way to make that chemotherapy more effective (a chemosensitizer), not as a standalone cancer treatment.
Do the trial doses of lomeguatrib provide a dose I can use?
No. Reported Phase I/II trial doses (such as 40 mg/day for 5 days, or 10-day extended schedules) were research doses used in specific small studies together with chemotherapy, not an approved dose or a patient treatment instruction.
What was the main safety concern seen in lomeguatrib trials?
Hematologic toxicity (myelosuppression) was reported as the dose-limiting toxicity when lomeguatrib was combined with temozolomide in the trials reviewed. A full adverse-event profile was not established in the sources reviewed in this session.
What is the mechanism of action of lomeguatrib?
Lomeguatrib is a pseudosubstrate inhibitor of O6-methylguanine-DNA methyltransferase (MGMT), designed via O6-position modification of the guanine scaffold to inactivate MGMT while aiming to avoid the severe myelosuppression associated with an earlier-generation MGMT inhibitor, O6-benzylguanine. This is described in the secondary literature reviewed as a design intent, not a proven clinical safety advantage, since dose-limiting hematologic toxicity was still reported in the lomeguatrib plus temozolomide combination trials. Preclinical (animal) studies observed MGMT depletion in normal tissues and in subcutaneous melanoma tumor xenografts for up to 24 hours after a single 20 mg/kg dose of lomeguatrib.
What is the generic name of Lomeguatrib?
The generic name is lomeguatrib.
What class of drug is lomeguatrib?
Lomeguatrib is classed as: Investigational O6-methylguanine-DNA methyltransferase (MGMT) inhibitor; chemosensitizer.
References
- Lomeguatrib clinical-trial and mechanism summary (ScienceDirect Topics / Nature (British Journal of Cancer) / ASCO Publications)Search-aggregated secondary summaries of peer-reviewed lomeguatrib clinical-trial literature (Middleton MR et al., Phase I trial of lomeguatrib + temozolomide, British Journal of Cancer; Khan O et al., Phase I/II lomeguatrib dosing-schedule study; ASCO/JCO abstract on MGMT inhibition in solid tumors) · Not applicable — investigational compound, no country approval · dated 2026 · accessed 2026-08-05 · source 1
Brand names by country
Single-ingredient lomeguatrib names are shown separately by country. Product availability, strengths, and supply rules can change; combination products are not included here.