Mustargen (mechlorethamine)

In CT26 tumor-bearing mouse models, MN33-47 and MN33-63 exhibited significant dose-dependent tumor suppression without causing apparent toxic side effects, demonstrating superior safety compared to combination chemotherapy. In summary, this work provides a practical solution to overcome the clinical limitations of SN-38 and nitrogen mustard, primarily through molecular innovation that "solidifies" combination therapy into a single entity, thereby directly resolving the inherent conflict between enhancing efficacy and exacerbating toxicity.

ADA, NT5E and TYMS can serve as potential diagnostic markers and therapeutic targets for OSCC. The study has reference value for early diagnosis and the development of individualised treatment strategies.

Here, we developed an NTR-responsive PET strategy for in vivo tumor hypoxia imaging using radiolabeled nitrogen mustard analogues (18F-NTRP and 18F-NCRP)...Moreover, T/M ratios correlated well with HIF-1α (r2 = 0.71) and NTR (r2 = 0.66) levels in the A549 tumor. Collectively, PET imaging demonstrated that 18F-NCRP specifically targets tumor NTR and can potentially discriminate between varying degrees of hypoxia.

All patients were treated with chlormethine hydrochloride gel in combination with other skin-directed and systemic therapies, including bexarotene, methotrexate, topical steroids, extracorporeal photopheresis, donor lymphocyte infusion and interferon-α (IFN-α) 2a...The combination regimens were generally well tolerated, with associated adverse events being inflammation, pruritus and erythema. This case series reports on the efficacy and safety of chlormethine hydrochloride gel in combination with other topical and systemic therapies in reducing the skin lesion severity in patients with Stage I-IV MF in different real-world settings.

P1, N=24, Recruiting, General Oncology, Inc. | N=10 --> 24 | Trial completion date: Aug 2027 --> Dec 2028 | Trial primary completion date: Aug 2026 --> Dec 2028

Dna2 mutants demonstrated significant sensitivity to replication stress induced by MMS, hydroxyurea, topotecan, and nitrogen mustard. Dna2lS/S1 mutants exhibited higher survival than Dna2lS/D2 upon exposure to topotecan and bleomycin, suggesting a possible helicase-specific role in damage response...These insights clarify the nuanced contributions of the nuclease and helicase domains of DNA2, suggesting potential domain-specific functions in genomic stability and repair mechanisms. This work provides a foundation that will enable future researchers to further dissect the complex roles of DNA2 in replication and repair pathways.

P1, N=10, Recruiting, General Oncology, Inc. | Trial completion date: Dec 2025 --> Aug 2027 | Trial primary completion date: Dec 2025 --> Aug 2026

Six months post-treatment, the patient remained in remission. This case underscores the effectiveness of CG in achieving sustained remission in acral LyP, suggesting its potential as a treatment option for this rare condition.

And moreover, AA also could reduce the content of TNF-α and IL-6. Overall, the present study showed that AA played an important protective effect in HaCaT cells exposed to NM through the inhibition of the ERS-induced apoptosis and inflammatory response.

To exploit this finding, we developed a novel prodrug, ACHM-025, which is selectively activated by AKR1C3 to a nitrogen mustard DNA alkylating agent...ACHM-025 was significantly more effective than cyclophosphamide both as a single agent and when used in combination with cytarabine/6-mercaptopurine. Notably, ACHM-025 in combination with nelarabine was curative when used to treat a chemoresistant T-ALL PDX in vivo. The in vivo efficacy of ACHM-025 directly correlated with AKR1C3 expression levels, providing a predictive biomarker for response. Together, our work provides strong preclinical evidence highlighting the potential of ACHM-025 as a targeted and effective therapy for aggressive forms of T-ALL.

In vivo experiments prove nanomicelle Mech02-HA NPs is able to activate immune memory effects and raise the persistence of anti-tumor immunity. In summary, this study for the first time to introduce the arsenic(III) pharmacophore as an enhanced ICD effect initiator into nitrogen mustard, providing insights for the development of efficient multimodal tumor therapy agents.

Additionally, in macrophages from both control and NM treated animals, NAC treatment resulted in increased S-nitrosylation of ATP synthase, protecting the enzyme from oxidative damage. Taken together, these data suggest that alterations in NM-induced macrophage activation and bioenergetics contribute to the efficacy of NAC in mitigating lung injury.