Samcyprone (diphenylcyclopropenone) / Phio Pharma - LARVOL DELTA

Anterior Cingulate Cortex Astrocytes Regulate Chronic Itch and Comorbid Negative Emotional Disorders in Mice. (PubMed, CNS Neurosci Ther) - "ACC astrocytes play a critical role in regulating chronic itch and comorbid anxiety-depression by modulating CaMKII-positive neuronal activity, providing a potential therapeutic target for intractable chronic itch in clinical settings."

Journal • Preclinical • CNS Disorders • Depression • Mood Disorders • Psychiatry

Drug-associated vitiligo: A systematic review of therapies, clinical patterns and mechanisms. (PubMed, Clin Exp Dermatol) - "Drug-associated vitiligo represents a heterogeneous spectrum of disorders spanning multiple therapeutic classes. While recurrent clinical patterns and biologically plausible mechanisms support a contributory role for several drug classes, causality remains uncertain for many reported associations. Recognition of characteristic clinical and temporal patterns may improve patient counselling, inform treatment decisions and guide future pharmacovigilance and mechanistic research."

Journal • Dermatology • Immunology • Melanoma • Oncology • Solid Tumor • Vitiligo

Evaluation of hematological parameters and treatment response in patients with alopecia areata treated with diphenylcyclopropenone: an exploratory retrospective study. (PubMed, Cutan Ocul Toxicol) - "Significant changes were observed in lymphocyte counts(p = 0.01) and the platelet-to-lymphocyte ratio(PLR, p = 0.02) following treatment.When evaluating which hematological and inflammatory parameters predicted the SALT score at Month 6, an exploratory regression analysis(Adjusted R2 = 0.101) showed that only the change in lymphocyte levels was associated with treatment response(β = 0.354, p = 0.029). Conclusion Our findings suggest that, based on sixmonth evaluation results,DPCP may be an effective treatment option for AA.While it modulates local inflammation, it appears to have a limited effect on systemic immunity; however, this does not result in any significant adverse alterations in hematological and inflammatory biomarkers.Current data suggest that topical DPCP treatment demonstrated a potentially acceptable hematological safety profile in the short-tomedium term.Furthermore, the change in lymphocyte levels may emerge as a potential biomarker for predicting..."

Journal • Retrospective data • Alopecia • Hematological Disorders • Immunology • Inflammation

Gallylene-Mediated C-C Bond Activation of Diphenylcyclopropenone and Chalcogen Atom Insertion into a Ga-C Bond. (PubMed, ACS Org Inorg Au) - "Density functional theory (DFT) calculations suggest that the oxidative addition proceeds through nucleophilic attack of the gallylene on the alkene moiety of the cyclopropenone, ring opening with C-C bond cleavage to generate a ketene intermediate, and subsequent cyclization through Ga-C bond formation. The resulting four-membered gallacycle undergoes oxygen- and sulfur-atom insertion reactions into the Ga-C-(O) bond, affording the corresponding five-membered gallacycles."

Journal

Trem-1 and Ultraviolet Radiation-induced Immune Suppression (clinicaltrials.gov) - P1 | N=70 | Active, not recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Oct 2026 ➔ Oct 2027 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Dermatology

Diarylcyclopropenones: Modular, Tetherable, Light-Triggerable Reservoirs of Carbon Monoxide in Crosslinked Hydrogels. (PubMed, ACS Appl Bio Mater) - "We recently demonstrated that diphenylcyclopropenone (DPCP) serves as a highly efficient, visible-light-triggered CO-generating motif when incorporated into polymeric micelles...However, CO release into solution depends on hydrogel network properties and chemistry. These results establish diarylcyclopropenones as a modular, tetherable, light-triggerable reservoir of CO gas and hydrogels as a tunable platform for its use."

Journal

Identification and experimental validation of CD74, PGLYRP1, and TXN as potential biomarkers in rheumatoid arthritis: an integrative bulk and ScRNA-seq study. (PubMed, Front Immunol) - "By integrating bulk RNA sequencing with scRNA-seq, CD74, PGLYRP1, and TXN were identified as biomarkers, with myeloid cells suggested as a potential key cell type, providing new insights into RA diagnosis and meriting further investigation of their functional roles."

Biomarker • Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CD74 • TXN

The Impact of Prescription Therapies for Warts and Molluscum. (PubMed, Pediatr Clin North Am) - "This article focuses on familiarizing the pediatric provider with prescription topical therapies for both conditions including cantharidin, imiquimod, and retinoids, as well as berdazimer sodium for MC and 5-fluorouracil and diphenylcyclopropenone and Squaric Acid Dibutyl Ester for viral warts. Other therapies including injections and oral medications will also be discussed."

Journal • Review • Dermatology • Pediatrics

Real-World Efficacy Data of Oral Ritlecitinib in Severe Alopecia Areata: A Multicentre UK Experience (AAD 2026) - "Factors associated with a positive outcome included male sex (mean SALT reduction 29.8 at three months, 66.1 at six months; females 12.7, 35.1), prior systemic immunosuppressive therapy (76.0, 92.8 vs. 15.0, 38.2 without prior systemic use), and previous diphenylcyclopropenone (DCP) treatment (23.3, 51.8 vs. 20.1, 35.0 without DCP). Our study identified male sex, prior systemic therapy, and eyebrow/eyelash regrowth were associated with favourable response to oral Ritlecitinib for AA. These findings have implications on clinical practice in terms of patient selection and counselling."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Alopecia • Immunology • JAK3

Study on translational diffusion of solute molecules in novel phosphonium-based dicationic ionic liquids by transient grating spectroscopy. (PubMed, Phys Chem Chem Phys) - "Translational diffusion coefficients of carbon monoxide (CO), diphenylacetylene (DPA), and diphenylcyclopropenone (DPCP) were determined by transient grating (TG) spectroscopy in five ionic liquids (ILs), including novel phosphonium-based dicationic ionic liquids (DILs): 1,6-bis(trioctylphosphonium)hexane bis(trifluoromethanesulfonyl)amide ([(P888)2C6][NTf2]2) and 1,10-bis(trioctylphosphonium)decane bis(trifluoromethanesulfonyl)amide ([(P888)2C10][NTf2]2)...Moreover, the degree of deviation was almost independent of the alkyl linkage chain length. By comparing the diffusion coefficients of CO in monocationic ILs and DILs, it was found that the diffusion coefficient of CO was correlated with the volume per charge of the cation."

Journal

Efficacy and Safety of High-Dose Baricitinib in Adults with Severe Refractory Alopecia Areata: A Retrospective Study of 12 Patients (AAD 2026) - "The median disease duration was 4.5 years (range 0.08–21), with a median of 3.5 prior systemic therapies (range 2–7), most frequently systemic corticosteroids, methotrexate, and diphenylcyclopropenone...Subsequently, 10 patients were treated with 8 mg/day and 2 with 6 mg/day; 7 received concomitant oral minoxidil and 3 systemic corticosteroids... Baricitinib 6–8 mg/day may provide a therapeutic alternative for severe refractory AA after failure of the standard dose. Larger prospective studies with longer follow-up are needed to confirm these findings and define the long-term efficacy and safety profile."

Retrospective data • Alopecia • Immunology

Clinical outcome of alopecia areata in patients with atopic dermatitis treated with dupilumab combined with topical immunotherapy: a case series. (PubMed, Eur J Dermatol) - "A representative treatment began with sensitization using squaric acid dibutyl ester or diphenylcyclopropenone, followed by dupilumab monotherapy to control atopic dermatitis. Notably, 75% of patients who had previously failed topical immunotherapy tolerated concentrations up to 100-fold higher. Dupilumab combined with topical immunotherapy demonstrated favourable effects in alopecia areata patients with atopic dermatitis, offering a safer and effective option, especially for paediatric or oncology cases."

Clinical data • Journal • Alopecia • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Oncology • Pediatrics

DPCP for the Treatment of Alopecia Areata (clinicaltrials.gov) - P3 | N=4 | Terminated | Sponsor: University of Minnesota | N=10 ➔ 4 | Completed ➔ Terminated; The study was paused/enrollment on hold after 4 screen failed subjects. No further subjects were enrolled, therefore, no data was available to collect/analyze.

Enrollment change • Trial termination • Alopecia • Dermatology • Immunology

BH02 Overcoming genetic drivers in alopecia areata: hair regrowth in a patient with the AIRE gene mutation treated with ruxolitinib. (PubMed, Br J Dermatol) - "Previous treatments, including diphenylcyclopropenone and ciclosporin, were discontinued due to adverse side-effects. She also had a notable improvement in her quality-of-life scores (Dermatology Life Quality Index and Hospital Anxiety and Depression Scale) over the course of the 9 months. This case highlights the efficacy of Janus kinase inhibitors, in this case ruxolitinib, in severe AA associated with AIRE gene mutation."

Journal • Alopecia • Candidiasis • CNS Disorders • Depression • Dermatology • Developmental Disorders • Endocrine Disorders • Genetic Disorders • Hypoparathyroidism • Immunology • Mood Disorders • Nephrology • Pain • Psychiatry • Renal Disease • Sjogren's Syndrome

Treatment challenges in a case of refractory alopecia areata with partial response to sequential JAK inhibitor therapy (EADV 2025) - "Traditional treatments for AA, such as topical or systemic corticosteroids, topical minoxidil, cyclosporine, methotrexate (ΜΤΧ), and azathioprine, exhibit limited efficacy, particularly in moderate to severe cases...Additional therapies included topical dithranol, anthralin, and sensitization with diphenylcyclopropenone (DPCP)...She remains on ritlecitinib; nevertheless, mild ΑΕ have been observed (upper respiratory tract infections and herpes simplex outbreaks), similar to those she previously experienced with other JAKi therapies (tofacitinib, baricitinib), which required temporary interruption of systemic therapy for short periods (3–5 days)... The management of AA remains challenging. Various treatments are available, although relapses are often and some cases sustain resistant to therapy. Substantial evidence now supports the use of JAKi, particularly in patients with refractory disease."

Clinical • Alopecia • Herpes Simplex • Immunology • Infectious Disease • Respiratory Diseases

Recurrence of alopecia areata after complete hair regrowth with diphenylcyclopropenone : A retrospective long-term follow up analysis (EADV 2025) - "Recurrence of AA after complete hair regrowth with DPCP was associated with longer disease duration, recurrence history, thyroid dysfunction, and extra-scalp involvement. These findings contribute to a better understanding of AA management post DPCP treatment."

Retrospective data • Alopecia • Endocrine Disorders • Immunology

Nail matrix HPV infection: a rare and underrecognized form of subungual wart (EADV 2025) - "Cases achieving cure more frequently treated with imiquimod (71.4%, P=0.103) and oral zinc sulfate (100%, P=0.07)...One case showed a partial response to diphenylcyclopropenone. Nail matrix HPV infections present with diverse clinical features and frequently show limited response to conventional therapies. Early, accurate diagnosis combined with individualized treatment strategies may improve clinical outcomes in this challenging condition."

Dermatology • Human Papillomavirus Infection • Infectious Disease • Mood Disorders

Effectiveness of Combining Dupilumab and Topical Immunotherapy for Alopecia Areata Associated with Atopic Dermatitis (ESDR 2025) - "Treatment began with sensitization using TI agents, such as squaric acid dibutyl ester or diphenylcyclopropenone, followed by dupilumab administration to stabilize skin inflammation of AD. These findings suggest that combining dupilumab with TI may offer synergistic effects and possibly enhance efficacy and tolerability. This dual approach may represent a potentially promising treatment option for refractory AA with AD, especially in populations with limited therapeutic choices, such as patients with longer AA durations, pediatric cases, and patients with cancerous histories."

Alopecia • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pediatrics

Treatment outcomes and considerations for topical immunotherapy in patients with alopecia totalis and alopecia universalis. (PubMed, Front Med (Lausanne)) - "Topical immunotherapy with squaric acid dibutylester (SADBE) and diphenylcyclopropenone (DPCP) is widely used but has variable efficacy...Topical immunotherapy remains an effective treatment for severe alopecia areata, although response rates vary among patients. Individualized treatment approaches, including prolonged therapy and consideration of patient-specific factors, are essential for optimizing clinical outcomes."

Journal • Alopecia • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Randomized Controlled Trial Study to Evaluate the Efficacy of Combination Therapy with Diphenylcyclopropenone and Platelet-Rich Plasmain Alopecia Areaata. (PubMed, Int J Trichology) - "This is the first study to investigate a synergistic effect with DPCP and PRP. According to this study, PRP is ineffective as an adjunct to DPCP for augmenting its effectiveness."

Clinical • Journal • Alopecia • Immunology

Trem-1 and Ultraviolet Radiation-induced Immune Suppression (clinicaltrials.gov) - P1 | N=70 | Active, not recruiting | Sponsor: University of Alabama at Birmingham | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial primary completion date • Dermatology

Nanoparticle Adjuvants Incorporating Haptens Drive Potent Immune Tolerance to Accelerate Hair Regrowth. (PubMed, ACS Appl Mater Interfaces) - "This study introduces a nanoparticle (NP) system that codeliver diphenylcyclopropenone (DPCP) and rapamycin (RAPA) prodrugs to induce immune tolerance and promote hair regeneration. In vivo studies on a mouse model of alopecia showed that these NPs significantly accelerated the transition of hair follicles from the telogen phase to the anagen phase, promoting hair regrowth. This research presents a promising therapeutic strategy for AA and offers insights into treating autoimmune diseases where autoantigens are unclear."

Journal • Alopecia • Immunology

Topical and Intralesional Treatments for Skin Metastases and Locoregionally Advanced Melanoma. (PubMed, Cancers (Basel)) - "Diphenciprone, imiquimod and 5-florouracil were included as topical treatments and bacillus Calmette-Guerin, interleukin 2, rose bengal, talimogene laherparepvec and electrochemotherapy were included as intralesional treatments. Brief comments on other alternatives in development such as interferon-alpha, interleukin-12, ipilimumab and intralesional daromun are presented...It has also been described in a few papers that non-injected lesions may respond after the application of a local therapy in distant skin-metastases. Many of these intralesional treatments are being combined in different investigations with systemic immunotherapies, with the aim of obtaining synergic responses in those patients with refractory disease."

Journal • Review • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • IL12A • IL2

Thyrotropin-Releasing Hormone Analog Taltirelin Inhibits Acute and Chronic Itch in Mice. (PubMed, Biol Pharm Bull) - "Subcutaneous injection of chloroquine increased the number of scratching bouts in 30 min, whereas intraperitoneal injection of taltirelin reduced these episodes in a dose-dependent manner. In addition, chronic itch induced by diphenylcyclopropenone treatment was alleviated by taltirelin injection. These findings indicate that taltirelin alleviates acute and chronic itch in mice, and can be a potent therapeutic antipruritic drug."

Journal • Preclinical • Dermatology • Inflammation • Pain

Topical immunotherapy with diphenylcyclopropenone in paediatric patients with alopecia areata-A retrospective study of 97 patients. (PubMed, Skin Health Dis) - "One year after the onset of DPCP in paediatric AA patients, the complete response and any hair regrowth rates were 8.8% and 61.8%, respectively. The milder initial disease severity and longer duration of treatment resulted in a better response."

Journal • Retrospective data • Alopecia • Dermatology • Immunology • Pediatrics