Mustargen (mechlorethamine) / Recordati - LARVOL DELTA

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

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

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

Development of a Novel Approach for In Vivo Tumor Hypoxia PET Imaging with Nitroreductase-Specific Responsive Radiotracers. (PubMed, Mol Pharm) - "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."

Journal • Preclinical • Oncology • HIF1A

Management of Mycosis Fungoides With Chlormethine Hydrochloride Gel in Combination With Systemic Therapies: A Case Series. (PubMed, Case Rep Dermatol Med) - "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."

Journal • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Oncology • Pruritus • T Cell Non-Hodgkin Lymphoma • IFNA1

In Memoriam: Eugene Joseph Van Scott, MD (1922-2025). (PubMed, J Am Acad Dermatol) - No abstract available

Journal

SHARON: A Clinical Trial for Metastatic Cancer Using Chemotherapy and Patients' Own Stem Cells (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: General Oncology, Inc. | N=10 ➔ 24 | Trial completion date: Aug 2027 ➔ Dec 2028 | Trial primary completion date: Aug 2026 ➔ Dec 2028

Enrollment change • 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

Fenofibrate microemulsion eyedrops for treating nitrogen mustard induced corneal injury. (PubMed, J Control Release) - "Immunohistochemistry revealed that NM injury significantly reduced PPARα levels in the corneal epithelium, which was restored with Feno ME eyedrop treatment, suggesting PPARα as a promising drug target for NM-induced corneal injury. Our Feno ME eyedrop formulation represents an effective topical delivery platform that effectively mitigates NM-induced corneal injury and offers a novel therapeutic strategy for vesicant exposure."

Journal • Corneal Abrasion • Dyslipidemia • Inflammation • Keratitis • Metabolic Disorders • Ocular Inflammation • Ophthalmology • PPARA

Tumor-Selective and Chemical Activation Strategies for Nitrogen Mustard Prodrugs. (PubMed, Chemistry) - "We also discuss integration with advanced delivery platforms, including polymeric carriers and nanoplatforms, to enhance tumor accumulation and therapeutic indices while minimizing off-target toxicity. By consolidating recent advances, this review illustrates how bioorthogonal and tumor-selective activation strategies, including those responsive to hypoxia, ROS, and pH, are redefining the precision oncology potential of NM prodrugs."

Journal • Review • Oncology

Alterations in Mitochondrial DNA in Corneal Fibroblast and Myofibroblast Post Injury. (PubMed, Invest Ophthalmol Vis Sci) - "CMF formation was induced by transforming growth factor beta-1 (TGFβ1) in vitro and human cornea by nitrogen mustard (NM) ex vivo...We observed that mtDNA plays an important role in corneal fibroblast transdifferentiation to myofibroblast and that TFAM has the potential to modulate this process in an injured cornea. Additional studies are warranted."

Journal • Corneal Abrasion • Fibrosis • Immunology • TFAM • TGFB1

Losartan Alleviates Chemical Burn-Induced Limbal Stem Cell Deficiency: Repurposing a Venerable Anti-Hypertension Drug. (PubMed, Invest Ophthalmol Vis Sci) - "We utilized a nitrogen mustard (NM)-induced corneal injury model to create LSCD, characterized by conjunctivalization. Flow cytometry analysis confirmed that losartan attenuated corneal inflammation via reducing the monocytes/macrophages in the cornea. Our findings strongly support a new therapeutic use for losartan in blunting LSCD, which is a consequence associated with numerous corneal inflammatory conditions (e.g. diabetic keratopathy and tear gland insufficiency)."

Journal • Cardiovascular • Corneal Abrasion • Hypertension • Inflammation • Keratitis • Ocular Inflammation • Ophthalmology • Transplantation

Dose-dense chemotherapy enables elimination of RT for majority of low-risk pediatric Hodgkin lymphoma: PHC study HOD08. (PubMed, Blood) - P2 | "Treatment consisted of a modified 8-week Stanford V regimen (vinblastine, doxorubicin, vincristine, bleomycin, mechlorethamine, etoposide and prednisone). A dose-dense modified Stanford V regimen reduced the proportion of low-risk pediatric patients with HL who received RT while maintaining excellent outcomes. NCT00846742."

Journal • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Pediatrics

Mechanisms, pathological features, and intervention strategies for nitrogen mustard-induced skin toxicity. (PubMed, Toxicol Lett) - "Evidence suggests that NM-induced toxicity develops as a cascade of interconnected processes, where genotoxic stress, oxidative imbalance, and innate immune activation mutually reinforce each other. Based on this framework, we outline available intervention strategies and discuss promising directions for future studies."

Journal

In Situ Evaluation of the GSH Depletion Ability of Various Alkylating Agents and the Protective Effect of Several Active Thiol Compounds Based on High-Content Cell Analysis. (PubMed, Toxics) - "The results showed that bis(2-Choroethyl) methylamine (nitrogen mustard, HN2) and 1,2-bis(2-chloroethythio) ethane (Q) exhibited the highest cytotoxicity, with IC50 values of 14.45 μM and 23.27 μM, respectively...The results revealed that reduced glutathione ethyl ester (GSH-MEE) was most effective in preventing GSH depletion, whereas glutathione monoethyl ester (MEE) showed the highest efficacy in restoring GSH levels. The proposed method holds significant potential for analyzing the damaging effects of various alkylating agents and screening protective drugs."

Journal

DNA binding and lesion recognition by the bacterial interstrand DNA crosslink glycosylase AlkX. (PubMed, bioRxiv) - "Mutational analysis of ICL unhooking in vitro and A. baumannii sensitivity to the crosslinking agent mechlorethamine enabled identification of several AlkX motifs critical for ICL repair. We also found that a genetic variant from an antibiotic-resistant strain of the human pathogen Salmonella enterica significantly reduced AlkX activity in vitro and increased 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

Real-World Determinants of Olanzapine Prescribing for Antiemetic Prophylaxis in Adults Receiving Highly-Emetogenic Chemotherapy. (PubMed, Hosp Pharm) - "Since 2017, guidelines recommend a four-drug prophylactic antiemetic regimen-5HT3 receptor antagonist (5HT3RA), NK1 receptor antagonist (NK1RA), dexamethasone, and olanzapine-for patients receiving highly emetogenic chemotherapy (HEC)...Adults ≥21 years initiating cisplatin, carmustine, dacarbazine, mechlorethamine, streptozocin, or cyclophosphamide plus anthracycline (AC) in 2022 were included...Despite guideline recommendations, prophylactic olanzapine use in HEC remains suboptimal, influenced by clinical and non-clinical contextual factors. Targeted efforts at information dissemination and updated prescribing systems are needed to promote equitable, evidence-based supportive care."

Journal • Real-world evidence • Chemotherapy-Induced Nausea and Vomiting • Hematological Disorders • Hematological Malignancies • Oncology

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