Mustargen (mechlorethamine) / Recordati - LARVOL DELTA

Targeting DNA repair vulnerabilities to eradicate TP53 mutated AML. (ASH 2025) - "Current treatment strategies, includingconventional chemotherapy, hypomethylating agents, and venetoclax-based therapies, have shown limitedefficacy in TP53mut AML, with low response rates and poor overall survival...XPC and DDB2 are the key proteins in the global genome NER (GG-NER).GG-NER removes bulky melphalan (a nitrogen mustard used in the management of multiple myeloma) DNAmonoadducts, but not irofulven-mediated DNA damage which is recognized by transcription-coupled NER (TC-NER)...We are currently testing the combination of melphalan and RAD51i in mice carrying TP53mut AML.We pinpointed the "Achilles heels" of DDR in TP53mut AMLs: stimulation of HRR and downregulation of GG-NER. These weaknesses were successfully targeted by the combination of RAD51i which attacks HRR andmelphalan which explores GG-NER deficiency."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • BRCA2 • DDB2 • HRD • RAD51 • TP53 • XPC

Amino alkyl-alkyl/aryl sulphides (DRDE-07 and analogues) as promising cytoprotectants for sulphur and nitrogen mustards - A review. (PubMed, Toxicol Rep) - "These compounds showed better protection compared to other experimented molecules, such as amifostine, N-acetylcysteine, melatonin, sodium thiosulphate, and flavonoids...Among them, DRDE-30 showed the best protection for SM and nitrogen mustards, as well as against radiation, and also as a cytoprotectant for anticancer agents. In this review, all the published papers on the DRDE series of compounds are compiled and discussed, with the aim that if any one of these molecules is recommended as an oral prophylactic drug, further development would occur for a more effective, broad-spectrum cytoprotectant."

Journal • Review • Oncology

H2O2-Responsive Anticancer Prodrug: Synthesis, Precision Deuteration in Search of In Vivo Metabolites, and Activation Pathway. (PubMed, J Med Chem) - "We report a novel H2O2-responsive phenylboronic nitrogen mustard prodrug (10a) and its precisely deuterated analogue (10b), designed to elucidate the activation pathway of ROS-responsive agents...Prodrug 10a exhibited H2O2-inducible DNA-alkylating activity, selectively inhibited the proliferation of high ROS-expressing MDA-MB-468 cancer cells over nonmalignant MCF-10A cells, markedly suppressed tumor growth without observable toxicity. This study highlights precision deuteration as a mechanistic probe and establishes a platform for rational design and optimization of boron-based anticancer prodrugs."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

The Efficacy and Safety of Zanubrutinib, Dexamethasone and or Not Cyclophosphamide Regimen in Symptomatic Waldenstrom Macroglobulinnemia (ASH 2023) - "After 8 cycles, patients with VGPR remission receive Chlorambucil 6mg D1-4,15-18, dexamethasone 20mg D1-4,15-18, cyclophosphamide 300mg, D1-4,15-18 for 4cycles, others receive Zanubrutinib as maintenance. These results demonstrate that zanubrutinib, dexamethasone and or not cyclophosphamide are quickly effective in the treatment of WM, with more deeper response and less toxicity, maybe treatment discontinued by combining with cyclophosphamide after deep remission. Comments*The regimen of ZD: Zanubrutinib 240mg d1-28, dexamethasone 20mg D1-4,15-18. Patients more than 75 years old, Zanubrutinib 160mg d1-28, dexamethasone 10mg D1-4,15-18."

Clinical • Atrial Fibrillation • Cardiovascular • Diabetes • Hematological Disorders • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Neutropenia • Thrombocytopenia • Waldenstrom Macroglobulinemia • CXCR4

Validation of Childhood Hodgkin International Prognostic Score (CHIPS) for Predicting Event-Free Survival in Intermediate and High-Risk Hodgkin Lymphoma (ASH 2023) - P2, P3 | "The Childhood Hodgkin International Prognostic Score (CHIPS) was developed as a predictive model for event-free survival (EFS) in pediatric and adolescent HL using clinical data at diagnosis from patients with intermediate-risk HL treated on Children's Oncology Group protocol AHOD0031 (NCT00025259) with doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy and response-adapted radiation...All patients received 12 weeks of Stanford V chemotherapy with doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone followed by low-dose, response-adapted radiation therapy... CHIPS is highly predictive of EFS in pediatric and adolescent patients with intermediate and high-risk HL treated with Stanford V chemotherapy, as it identifies a subset (CHIPS 2-4) with significantly lower EFS compared to the other subset (CHIPS 0-1). Assessment of CHIPS alongside novel approaches such as..."

Clinical • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Pediatrics

Post-Transplant Bendamustine Extends Survival and Reduces GvHD in a Xenogeneic NSG Transplant Model Compared to Post-Transplant Cyclophosphamide (ASH 2024) - "Our laboratory has investigated the use of bendamustine, another nitrogen mustard agent, as a post-transplant GvHD prophylaxis. Ongoing experiments include investigation into the early deleterious effects of PT-CY on murine CD45+ populations and use of xenogeneic GvL models to examine whether the engrafted cells maintain a GvL effect in the presence of reduced GvHD. Additionally, single cell RNA-sequencing on engrafted hCD45+ cells will be performed to assess changes in gene expression across T-cell populations in xGvHD mice treated with either PT-CY or PT-BEN."

Post-transplantation • Acute Graft versus Host Disease • Bone Marrow Transplantation • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • PTPRC

An Unusual Presentation of Mycosis Fungoides with Elevated Serum Tryptase (ACAAI 2025) - "He was initiated on omalizumab for persistent urticaria with partial improvement...He started treatment with mechlorethamine, showing good response...Discussion Although MF has not been associated with elevated tryptase levels, this patient’s persistently elevated tryptase with a negative evaluation for systemic mastocytosis raises questions about a potential association. This case also highlights the importance of thorough evaluations in patients with benign appearing, but persistent and refractory rashes, as conditions like MF may be overlooked."

Cardiovascular • Cutaneous T-cell Lymphoma • Dermatitis • Dermatology • Immunology • Mycosis Fungoides • Oncology • Urticaria • KIT

Phase 1 Dose Escalation of Single-Agent Mechlorethamine in Dogs With Lymphoma. (PubMed, Vet Comp Oncol) - "A higher dose of mechlorethamine than previously reported can be safely administered as a single agent to dogs. Increasing the dose of mechlorethamine in combination therapies might offer greater therapeutic benefits."

Journal • P1 data • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Oncology

Dna2 Responds to Endogenous and Exogenous Replication Stress in Drosophila melanogaster. (PubMed, Genes (Basel)) - " 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."

Journal • Solid Tumor • DNA2

Hecogenin‑nitrogen mustard hybrids with improved anti-breast cancer activity: Design, synthesis, and biological evaluation. (PubMed, Bioorg Chem) - "To enhance the efficacy of hecogenin (HCG) against breast cancer cells, we designed and synthesized two series of new HCG‑nitrogen mustard hybrids (4a-4f and 5a-5f) by linking benzoic acid mustard or chlorambucil to HCG via amino acid residues. Preliminary mechanism studies indicated that hybrid 5d induced G2/M phase arrest and apoptosis via the mitochondria-related apoptotic pathway, as well as caused DNA damage. Collectively, these results suggest that hybrid 5d is a promising lead compound for anti-breast cancer research worthy of further investigation."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Synthesis, Clastogenic and Cytotoxic Potential, and In Vivo Antitumor Activity of a Novel N-Mustard Based on Indole-3-carboxylic Acid Derivative. (PubMed, Molecules) - "Compound T1089-a novel nitrogen mustard based on an indole-3-carboxylic acid derivative (ICAD)-has been synthesized...The bifunctional alkylating agent cyclophosphamide (CPA) was used as a reference drug...Given that the ICAD used as the basis for T1089 is a TLR agonist capable of stimulating antitumor immunity, T1089 can be considered a dual-action alkylating agent with combined antitumor effects. These results justify further investigation of T1089 in conventional and metronomic chemotherapy regimens, particularly in combination with immune checkpoint inhibitors and antitumor vaccines."

Journal • Preclinical • Lung Cancer • Melanoma • Oncology • Solid Tumor

Zeb1 Facilitates Nitrogen Mustard-Induced Corneal Epithelial Wound Healing by Maintaining Epithelial Renewability. (PubMed, Invest Ophthalmol Vis Sci) - "Monoallelic knockout of Zeb1 decreased NM-induced acute epithelial damage but delayed the recovery from the damage. Zeb1 facilitates NM-induced corneal epithelial wound healing by maintaining epithelial renewability and thus is a potential therapeutic target to reduce acute mustard gas keratopathy in early ocular pathogenesis."

Journal • Ophthalmology • ZEB1

SHARON: A Clinical Trial for Metastatic Cancer With a BRCA or PALB2 Mutation Using Chemotherapy and Patients' Own Stem Cells (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: General Oncology, Inc. | Trial completion date: Dec 2025 ➔ Aug 2027 | Trial primary completion date: Dec 2025 ➔ Aug 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • BRCA1 • BRCA2 • HER-2

Dual-responsive fluorescent sensors for the detection and discrimination of sulphur and nitrogen mustards. (PubMed, Analyst) - "Mustard agents, including sulphur mustard (SM) and nitrogen mustard (NM), are chemical warfare agents that can cause blistering of the skin and mucous membranes upon contact...SN-R2-2 holds promise for military and public safety emergencies, enhancing chemical incident response and medical triage. To the best of our knowledge, SN-R2-2 is the first sensor for SM and NM discrimination."

Journal

Dr. Jane C. Wright (1919-2013): The Architect of Modern Chemotherapy and Clinical Oncology. (PubMed, Cureus) - "Over a career spanning 40 years, she and her collaborators pioneered human tissue-culture methods to test anti-cancer drugs, introduced nitrogen mustard and methotrexate therapies, and advocated for novel multi-drug combination regimens. Wright's scientific contributions in chemotherapy development and clinical research, her personal and educational background (including the influence of her father, Dr. Louis T. Wright), and her enduring impact on cancer care and medical leadership."

Journal • Review • Oncology

Targeted synergistic anticancer therapy by ascorbate-enabled reactive oxygen species generation and H2O2 responsive prodrug activation (ACS-Fall 2025) - "This study investigates a novel strategy utilizing Ascorbate to enhance hydrogen peroxide levels in cancer cells, thereby selectively activating boronated nitrogen mustard prodrugs (FAN-NM-CH3) to induce DNA alkylation and selective cell killing in multiple cancer types...These findings highlight the promise of this combination therapy in preclinical models and warrant further investigation in patient-derived xenograft (PDX) models. Future studies aimed at elucidating the underlying molecular mechanisms will enhance the therapeutic potential of this approach, ultimately paving the way for more selective and less toxic cancer therapies."

Breast Cancer • Oncology • Solid Tumor

Examination of a Chimeric Bis-Electrophile for Selective DNA-Protein Cross-Linking and Mechlorethamine Reveals an Unknown Source of Nitrogen Mustard Cytotoxicity. (PubMed, J Am Chem Soc) - "Proteomic analysis identifies several cysteine-rich E3 ligases involved in ubiquitination that are cross-linked to DNA in MCE-treated but not MEBAC-treated cells and suggests a chemical basis for why DPCs produced by the nitrogen mustard are not repaired by the proteasome. This investigation reveals a previously unknown source of nitrogen mustard cytotoxicity and indicates that MEBAC and molecules like it will be useful tools for studying DPCs in cells."

Journal • Targeted Protein Degradation

Structural and functional characterization of DNA glycosylases that repair crosslinked and intercalated DNA adducts arising from genotoxic natural products (ACS-Fall 2025) - "AlkX excises ICLs derived from the nitrogen mustard mechlorethamine, protects A. baumannii from alkylation and acid stress, and aids A. baumannii colonization of the lungs and dissemination to distal tissues during pneumonia (Kunkle, Cai et al, 2024, PNAS 121: e2402422121). Here, I will describe a crystal structure and mutational analysis of AlkX that provides a molecular basis for ICL repair by the YcaQ/AlkX family of DNA glycosylases."

Infectious Disease • Pneumonia • Respiratory Diseases • BCAT1

Topical Chlormethine Gel in the Treatment of Lymphomatoid Papulosis: A Case Report and Literature Review. (PubMed, J Clin Med) - "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."

Journal • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • TNFRSF8

Nitrogen mustard causes progressive tissue injury, severe DNA damage, and necroptosis in the cornea. (PubMed, Exp Eye Res) - "Finally, in cultured porcine corneas, the inhibition of necroptosis resulted in the prevention of corneal tissue destruction caused by NM. Our data suggest that the severity of NM-induced corneal injuries may be linked to increased necroptosis, and targeting necroptosis may reduce or prevent corneal deterioration caused by NM exposure."

Journal • Corneal Abrasion • Keratitis • Ocular Inflammation • Ophthalmology • CASP3

DFT studies of metal oxide nanocluster as a possible drug delivery system for mechlorethamine. (PubMed, BMC Chem) - "Thus, the interactions mentioned in this series are related to hydrogen bonds. Accordingly, based on the results obtained, Mg12O12 nanoclusters can be used as a promising carrier for ME drug delivery."

Journal • Oncology

Skin-Directed Therapies in Mycosis Fungoides: An Update. (PubMed, Dermatol Ther (Heidelb)) - "This review provides an updated overview of SDTs in MF treatment, including topical agents such as corticosteroids, retinoids, mechlorethamine, carmustine, imiquimod, as well as photodynamic therapy (PDT); phototherapy modalities including narrowband UVB (nb-UVB) and psoralen-UVA (PUVA); local radiotherapy; total skin electron beam radiotherapy (TSEBT) and total skin helical tomotherapy (TSHT). We review the indications, mechanisms of action, efficacy data, and adverse effect profiles associated with both established and emerging SDTs. Additionally, we present ongoing clinical trials evaluating emerging SDTs in the treatment of MF."

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

Treatment of Nitrogen Mustard-Induced Corneal Injury with Alpha-Melanocyte Stimulating Hormone. (PubMed, Exp Eye Res) - "These findings highlight the cytoprotective and anti-inflammatory effects of α-MSH. By mitigating NM-induced injury, α-MSH preserves corneal structural integrity and function, demonstrating its potential as a therapeutic intervention for mustard gas keratopathy."

Journal • Corneal Abrasion • Inflammation • Keratitis • Ocular Inflammation • Ophthalmology

Photodynamic therapy promotes hypoxia-activated nitrogen mustard drug release. (PubMed, Smart Mol) - "Meanwhile, the commercial photosensitizer Ce6 can aggravate the oxygen-poor state during the PDT process and further cause more AZOM release. Moreover, the cascade reactions in the nanosystem could activate singlet oxygen and enhance drug release through 660 nm light laser irradiation, contributing to more effective induction of tumor apoptosis and tumor growth retardation in vitro and in vivo."

Journal • Oncology • Solid Tumor

In Vivo Evidence of Melatonin's Protective Role in Alkylating-Agent-Induced Pulmonary Toxicity: A Systematic Review. (PubMed, Antioxidants (Basel)) - "In all cases, melatonin demonstrated protective effects against alkylating agents such as mechlorethamine (HN2) and cyclophosphamide (CP). Melatonin's pleiotropic mechanisms, including a reduction in oxidative stress, the modulation of inflammatory pathways, and support for tissue repair, reinforce its therapeutic potential in both prophylactic and treatment settings for alkylating agent exposure. Nonetheless, this review underscores the critical need for further randomized clinical trials to establish the optimal dosing strategies, refine treatment protocols, and fully elucidate melatonin's role in managing alkylating-agent-induced pulmonary toxicity."

Clinical • Journal • Preclinical • Review • Inflammation • Pneumonia