Mustargen (mechlorethamine) / Recordati - LARVOL DELTA

Concentration of Mechlorethamine Prescribing Among a Small Number of Specialists: Implications for Access to Cutaneous T-Cell Lymphoma Care. (PubMed, J Am Acad Dermatol) - No abstract available

Journal • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Oncology • T Cell Non-Hodgkin Lymphoma

Nucleophilic Selectivities of aliphatic electrophiles for Swain-Scott analysis: Fully protic and aqueous, green media, including hypoxia, and non-nucleophilic solvents | Poster Board #1680 (ACS-Fall 2026) - "Study of bendamustine showed rapid NBP alkylation and an s = 0.74 which we reported in 2018. Study of evofosfamide (TH-302) showed dramatic increases in NBP alkylation under anoxic conditions but with low s = 0.57 and low aerobic 6.5% alkylating activity (AA) vs. bis-(2-chloroethyl)amine (nor-HN2)(s = 0.98)...Extent of AA has been found predictive of dosing of ethyleneimines, from chlorambucil and mechlorethamine through the oxazaphosphoramines, cyclophosphamide and ifosfamide. Melflufen showed evidence of slow biphasic NBP alkylation consistent with peptide hydrolysis."

DNA-Peptide Crosslinks Placed at Codon 249 of the p53 Tumor Suppressor Gene Induce G to A Transitions in Human Cells. (PubMed, Chembiochem) - "Anticancer nitrogen mustard drugs including cyclophosphamide, mechlorethamine and chlorambucil induce covalent DNA-protein cross-links (DPCs) by sequentially alkylating the N7 position of guanine in DNA and amino acid residues within proteins. Pol η and Pol ι knockouts led to increased error rates, suggesting they play a role in error-free bypass of DpCs. In contrast Pol ζ deficiency reduced mutation rates, implying that it plays a role in error-prone bypass."

Journal • Oncology • TP53

Topical synthetic melanin nanoparticles mitigate chemically induced skin injury and promote wound repair (ACS-Fall 2026) - "Acute skin injury caused by nitrogen mustard (NM) exposure is characterized by excessive production of reactive oxygen species (ROS) and a robust inflammatory response that delays tissue repair...The protective effects of MEL-502 were further validated in human skin explants, where treated samples exhibited significantly reduced subepidermal blister formation following NM exposure compared to controls (p = 0.04, n = 6). Collectively, these findings demonstrate that topically applied synthetic melanin nanoparticles, specifically MEL-502, effectively mitigate chemically induced skin injury, modulate inflammatory responses locally and systemically, and accelerate wound healing."

Inflammation • CXCL1 • CXCR2 • IL10

NeuSolv: a rapid, safe, and effective nucleophile-based decontaminant for chemical warfare agents | Poster Board #1015 (ACS-Fall 2026) - "Chemical warfare agents (CWAs) such as nitrogen mustard (NM), sulfur mustard (SM), and nerve agents exhibit significant dangers due to their extreme toxicity and enduring presence in the environment...Moreover, NeuSolv is non-corrosive, less toxic, surface compatible, and can be formulated in wipes, sprays, as well as gels, which makes it ideal for real-world applications. Overall, NeuSolv is a highly promising decontaminant for CWAs in war field applications, laboratory settings, and emergency response situations, where rapid, safe, and material-friendly decontamination is needed."

NeuSolv: a rapid, safe, and effective nucleophile-based decontaminant for chemical warfare agents | Poster Board #1015 (ACS-Fall 2026) - "Chemical warfare agents (CWAs) such as nitrogen mustard (NM), sulfur mustard (SM), and nerve agents exhibit significant dangers due to their extreme toxicity and enduring presence in the environment...Moreover, NeuSolv is non-corrosive, less toxic, surface compatible, and can be formulated in wipes, sprays, as well as gels, which makes it ideal for real-world applications. Overall, NeuSolv is a highly promising decontaminant for CWAs in war field applications, laboratory settings, and emergency response situations, where rapid, safe, and material-friendly decontamination is needed."

Exploiting redox vulnerabilities for selective cancer therapy via ascorbate-driven prodrug activation | Poster Board #1179 (ACS-Fall 2026) - "Here, we describe a biologically driven therapeutic strategy that exploits cancer-specific redox vulnerabilities by combining pharmacological ascorbate (vitC) with a hydrogen peroxide (H2O2)-responsive nitrogen mustard prodrug (FAN-NM-CH3)...Clonogenic assays showed near-complete loss of colony formation in MDA-MB-468 cells, while deferoxamine (DFO) and catalase partially restored survival, demonstrating that iron-dependent oxidative stress and H2O2 flux are critical for sustained anticancer effects...Ongoing studies include evaluation in patient-derived xenograft (PDX) models and glioblastoma (U87) xenografts, as well as RNA sequencing to identify key pathways and biomarkers underlying treatment response. Collectively, these findings demonstrate that targeting cancer-specific redox imbalance provides a powerful strategy for selective therapy and supports further development of redox-based combination treatments."

Brain Cancer • Breast Cancer • Glioblastoma • Oncology • Solid Tumor • CAT

Surface chemistry-guided interfacial energetics of polydopamine-based synthetic melanin for topical skin repair (ACS-Fall 2026) - "Polydopamine (PDA)-based synthetic melanin particles are promising topical materials for tissue repair, as PDA has been shown to improve wound healing in nitrogen mustard injury models through its intrinsic radical scavenging activity...Ongoing work extends this framework to hydrophobic and cationic ligands to test whether simultaneous enhancement of lipid affinity and favorable electrostatics can improve PDA–skin association. Together, this work establishes a simple physicochemical design framework for next-generation PDA-based synthetic melanin therapeutics."

Solar-Driven TiO2 Photocatalytic Degradation of Live Chemical Warfare Agents: Performance Evaluation and Mechanistic Analysis. (PubMed, Molecules) - "Beyond military applications, this solar-assisted photocatalytic approach provides mechanistic information relevant to the green remediation of highly toxic organic contaminants and broader chemical hazard mitigation. This work contributes foundational knowledge toward eco-friendly decontamination technologies capable of mitigating diverse CWA threats."

Journal

Interaction of nitrogen mustard agents and their simulant with zinc oxide surfaces: a density functional theory study. (PubMed, Phys Chem Chem Phys) - "Multiple analyses consistently support adsorption-induced electronic redistribution. These results provide atomistic insight into the relationship between adsorption geometry, charge redistribution, and electronic response at oxide surfaces, and rationalize the similar behaviour of structurally different molecules at the ZnO interface."

Journal

DKK1 Targeting in Corneal Schwann Cells Rescues Axonal Regeneration and Mechanosensory Function After Corneal Injury. (PubMed, J Neurosci Res) - "We utilized the proteolipid protein 1-enhanced green fluorescent protein (Plp1-eGFP) reporter mice to investigate cSCs in two models of corneal nerve injury: the corneal micropocket injury (CMI) model, which causes focal stromal axonal severance, and acute exposure to nitrogen mustard (NM), which results in blunt damage across the entire cornea and limbal tissue...Application of RM4404 during the cSC regenerative phase (7-14 dpi) enhanced cSC repair and significantly improved axonal regeneration with restoration of mechanosensory function in both injury paradigms. These findings identify a promising DKK1-targeted therapy that promotes cSC repair, enhances corneal nerve regeneration, and restores sensory function in models of corneal injury."

Journal • Corneal Abrasion • DKK1 • PLP1

Nitrogen Mustard Disrupts Bioenergetics and Activates Oxidative Stress-Induced Cell Death Pathways in Human Keratinocytes. (PubMed, Chem Res Toxicol) - "Nitrogen mustard (HN2) is a highly reactive bifunctional alkylating agent that causes severe skin injury. N-acetylcysteine attenuated Nrf2 activation, preserved mitochondrial and glycolytic function, and reduced activation of cell death pathways, demonstrating a central role for oxidative and electrophilic stress in HN2 toxicity. These findings reveal a novel mechanism by which HN2 disrupts keratinocyte bioenergetics to drive stress-dependent cell death and highlight antioxidant intervention as a potential strategy to mitigate HN2-induced skin injury."

Journal • Metabolic Disorders • ACSL4 • BCL2L1 • CASP9 • GPX4 • NQO1 • SQSTM1

Tromethamine‑Modified Chlorambucil Prodrug Nano-Micelles: Improved Colloidal Stability and Antitumor Efficacy. (PubMed, Int J Nanomedicine) - "In vivo, the nanoformulation achieved superior tumor suppression in A20 tumor-bearing mice (final tumor volume 421 mm3 vs. 610 mm3 for free CLB and 1424 mm3 for saline), while maintaining excellent hemocompatibility (hemolysis <5%) and minimal systemic toxicity as evidenced by body weight stability and histopathological analysis. This carrier-minimized prodrug platform concurrently overcomes the solubility, stability, and toxicity bottlenecks of nitrogen mustard chemotherapy, offering a simple and translatable strategy for enhancing the clinical efficacy of chlorambucil."

Journal • Hematological Disorders • Hematological Malignancies • Lymphoma • Oncology

Erythrodermic Mycosis Fungoides with Palmoplantar Keratoderma and Nail Dystrophy: A Case Report (EADV-Sp 2026) - "Previous reports suggest variable efficacy of radiotherapy, phototherapy, CO₂ laser, and methotrexate, whereas topical corticosteroids, acitretin, and bexarotene appear less effective for palmoplantar MF. No standardized treatment guidelines exist for MF-related nail disease, therapeutic options are limited to topical corticosteroids, retinoids, or nitrogen mustard, with inconsistent outcomes. Palmoplantar and nail involvement, though rare, should raise suspicion for MF, particularly in erythrodermic patients even in the absence of Sézary syndrome criteria. Optimal management may require a multimodal approach combining systemic therapy with targeted treatments for resistant acral sites, along with long-term maintenance to prevent relapse"

Case report • Clinical • Cutaneous T-cell Lymphoma • Dermatology • Dermatopathology • Hematological Malignancies • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Pruritus • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • CD4 • CD7 • CD8

Evidence for microvesicles and platelet-activating factor as effectors for nitrogen mustard-mediated toxicity (SID 2026) - "Together, these findings identify a novel PAFR– and ASM-dependent pathway potentially underlying NM-induced toxicity. Inasmuch as ASM inhibitors are available, these studies have translational implications."

Dermatitis • Inflammation • MVP

Topical melanin enhances acute wound healing (SID 2026) - "Cutaneous Nitrogen Mustard (NM) exposure is characterized by an increase in reactive oxygen species (ROS)-induced damage from an early influx of neutrophils and macrophage/monocytes that prolongs the I-phase and consequently delays transition to the P-phase of healing...Taken together, these data suggest that SMP treatment enhances wound healing by promoting an earlier transition to P-phase, an effect that could be explained by reduced ROS-induced prolonging of I-phase. SMP treatment thus shows promise as a candidate for clinical use in minimizing iatrogenic effects such as inflammation during chemotherapeutic treatment."

Inflammation • ENO1 • GSTP1 • IL1B • IL23A • NLRP3

DNA binding and lesion recognition by the bacterial interstrand DNA crosslink glycosylase AlkX. (PubMed, EMBO Rep) - "Mutational analysis of ICL unhooking in vitro and A. baumannii sensitivity to the crosslinking agent mechlorethamine enable the identification of several AlkX motifs critical for ICL repair. We also find that a genetic variant from an antibiotic-resistant strain of the human pathogen Salmonella enterica reduces AlkX activity in vitro and increases A. baumannii sensitivity to DNA crosslinking. This work provides a structural basis for how bacterial ICL glycosylases recognize and repair DNA adducts and contributes additional evidence that ICL repair is important for fitness of human pathogens."

Journal

Design, synthesis and biological evaluation of novel chalcone analogs against castration-resistant prostate cancer. (PubMed, Biomed Pharmacother) - "A library of 16 novel cyclic or acyclic chalcones was designed and synthesized, incorporating substituted heterocyclic rings (pyrrole or pyridine) or nitrogen mustard...Additionally, in silico ADMET screening showed that OH16 exhibits favorable predicted drug-likeness properties. These findings suggest that thienyl-pyridine-based chalcones may serve as promising lead compounds against CRPC; thus, further in vitro and in vivo studies are warranted."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • CASP3

Metabolic rewiring renders KEAP1-mutant lung cancers sensitive to AKR1C3-activated prodrugs (AACR 2026) - "ACHM-025 is a second-generation AKR1C3-activated prodrug that is reduced in a single enzymatic step to ACHM-025H, a nitrogen mustard that bis-alkylates DNA to form intra- and interstrand cross-links (ICLs) leading to stalled DNA replication fork progression and cell death...Clonal competition assays admixing KEAP1-mutant and wild-type human adenocarcinoma cell lines demonstrated rapid depletion of KEAP1-mutant cells with minimal bystander effect. Finally, we confirmed that the cytotoxic effect of ACHM-025 led to increased phosphorylated H2AX (γH2AX) which is consistent with a mechanism of action involving DNA damage.Taken together, our data support the rationale that metabolic rewiring in KEAP1-mutant tumors leads to enhanced sensitivity to ACHM-025 and, therefore, supports AKR1C3 mediated prodrug activation as a potential therapeutic strategy for this subset of lung cancer patients."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • T Acute Lymphoblastic Leukemia • AKR1C1 • AKR1C3 • KEAP1 • KRAS • STK11 • TP53

P97 deficiency interferes with the recovery from acute nitrogen mustard-induced respiratory tract injury. (PubMed, Int Immunopharmacol) - "Collectively, these findings suggest that the perturbation of nucleic acid-associated biological processes constitutes the initial and critical event underlying the respiratory toxicity of NM. Furthermore, p97 deficiency impairs material transport, small-molecule metabolism, and mitochondrial function, and prolongs the recovery time in the aftermath of NM exposure."

Journal

Therapy-related mutational signatures in subsequent neoplasms among survivors of childhood cancer. (PubMed, Cancer Discov) - "Nitrogen mustard treatment correlated with elevated "flat" signature SBS5 in breast and meningioma SNs; in vitro, these agents caused an unresolved flat signature associated with multiple flat COSMIC signatures...Analysis of 19 multi-sample survivors revealed intrapatient heterogeneity in meningioma, including clonally independent tumors. These results demonstrate the long-term impact of childhood cancer treatment on the genomes of SNs developing in adulthood, which may guide SN treatment and prevention."

Journal • Brain Cancer • Meningioma • Oncology • Solid Tumor

Targeting the repair of DNA-protein crosslinks induced by bifunctional alkylating agents (AACR 2024) - "Micromolar concentrations of the nitrogen mustard mechlorethamine and nitrosourea lomustine induced significant DPC formation while more modest DPC formation was observed using similar concentrations of the chloroethylating agents carmustine and laromustine, as well as cisplatin. Chemotherapeutic sensitization by targeting SPRTN could suggest a therapeutic strategy to improve effectiveness of several DNA-targeted anticancer agents, especially if extended to other therapeutics that trap DPCs such as inhibitors of topoisomerase and poly(ADP-ribose) polymerase. Further, identifying structure-function relationships with respect to bifunctional alkylating agents and DPC formation could inform the future development and clinical utilization of these chemotherapies."

Hematological Malignancies • Leukemia • Oncology

Salt form and phosphate modification of an SN-38-nitrogen mustard conjugate: Overcoming water solubility limitations, combined efficacy, and broadened antitumor Spectrum. (PubMed, Bioorg Chem) - "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."

Journal • Oncology • BCL2 • CASP3

DNA-Protein Cross-Link Formation and Cellular Toxicity by Chimeric Bis-Electrophiles. (PubMed, J Org Chem) - "Comparisons between the reactivity of MEBAC and a nitrogen mustard with NCPs and nuclear lysates illustrate the advantage of the former for generating DPCs. m-MEBAC and MEBAC cytotoxicity in human cells are comparable and are enhanced when proteasomal DPC repair is inhibited. These experiments validate the utility of this family of chimeric bis-electrophiles as chemical tools for forming DPCs in the test tube and in cells."

Journal

Bioinformatics Identification and Functional Analysis of Key Genes of Nucleotide Metabolism in Oral Squamous Cell Carcinoma. (PubMed, Oral Health Prev Dent) - "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."

Biomarker • Journal • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • CD73 • MIR192 • MIR215 • MIR30A • MIR30B • NT5E • TYMS