Samcyprone (diphenylcyclopropenone) / Phio Pharma - LARVOL DELTA

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

Alopecia universalis in children and adolescents – treatment challenges (EADV 2024) - "Previous episodes of the disease have responded well to topical treatments and local immunotherapy with Diphenylcyclopropenone...The patient underwent treatment with 3 courses of systemic corticotherapy (Methylprednisolone) at monthly intervals and local treatment with dermatocorticoids, vitamin D analogs, Minoxidil solution and vasodilatory agents with no favorable evolution until present... The early onset in childhood and the family history of Alopecia areata provide a reserved prognosis of the case. Therapeutic options are limited to topical, intralesional or systemic corticosteroids, immunosuppressive agents or induction of allergic contact dermatitis, all of which has not showed favorable results in this patient. Currently, innovative therapies with Janus kinase (JAK) inhibitors such as Baricitinib have been approved in Romania for the adult population with promising results, which could be applicable for the presented case in the future."

Clinical • Alopecia • Contact Dermatitis • Dermatitis • Immunology • Pediatrics

DPCP for the Treatment of Alopecia Areata (clinicaltrials.gov) - P3 | N=10 | Completed | Sponsor: University of Minnesota | Recruiting ➔ Completed

Trial completion • Alopecia • Dermatology • Immunology

Baicalein ameliorates chronic itch in ACD mice by suppressing the spinal astrocytic STAT3-LCN2 cascade. (PubMed, Acta Pharmacol Sin) - "In this study, we explored the antipruritic effects of baicalein (BE), a bioactive flavonoid extracted from the root of Scutellaria baicalensis Georgi, and the underlying mechanisms in alleviating chronic itch triggered by diphenylcyclopropenone (DCP) in a mouse model of ACD...Schematic summary of the main findings illustrating that BE alleviates chronic itch through suppressing the spinal astrocytic STAT3-LCN2 cascade. Specifically, BE suppresses the expression of p-STAT3 to inhibit the reactive state of astrocytes in spinal dorsal horn, and then decreases the expression of astrocytic LCN2 to alleviate chronic itch in ACD mice."

Journal • Preclinical • Contact Dermatitis • Dermatitis • Dermatology • Immunology • STAT3

Preparation, solubility, and anti-inflammatory effects of a complex of diphenylcyclopropenone/β-cyclodextrin derivatives as the treatment of alopecia areata. (PubMed, J Pharm Pharm Sci) - "NMR analysis suggested that DPCP/β-CD and DPCP/HPβCD form inclusion complexes at a molar ratio of 1/1 but with different inclusion modes. The anti-inflammatory activity of DPCP was more pronounced in 3DGM (DPCP/HPβCD) at lower doses compared to that in 3DGM (DPCP/β-CD), indicating that the HPβCD derivatives were more effective in enhancing the anti-inflammatory properties of DPCP."

Journal • Alopecia • Immunology • IFNG

Synthesis of carbon monoxide releasing polymers (CORPs) via Ring opening metathesis polymerization (ROMP) (ACS-Fall 2024) - "Despite promising potential candidate, cytotoxicity and limited water solubility hampering its practical application in biological applications.Herein, we are developing a new class of polymer (Figure 1) containing a norbornene handle for polymerization and diphenylcyclopropenone (DPCP) for efficient release of CO gas via photolysis. Ring Opening Metathesis Polymerization (ROMP) with these monomers is fast, quantitative, simple, scalable, and can create block copolymers.3 CORPs will be engineered to produce non-toxic byproducts after the release of CO that are readily metabolized in the human body. In my presentation I will discuss the synthesis of monomers, ROMP, block copolymers and CO release triggered by blue light."

Factors Affecting the Response and Patient Satisfaction of Topical Immunotherapy in Alopecia Areata: A Nationwide Study. (PubMed, Ann Dermatol) - "DPCP immunotherapy is an effective treatment for AA, and the study demonstrated the factors affecting DPCP treatment response and patients' satisfaction and may contribute to standardizing the DPCP treatment method for better outcomes."

Journal • Allergic Rhinitis • Alopecia • Asthma • Atopic Dermatitis • Dermatitis • Dermatology • Endocrine Disorders • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Comparative efficacy and safety of systemic steroids, oral JAK inhibitors and Contact Immunotherapy in the Treatment of severe alopecia areata: a systematic review and network meta-analysis. (PubMed, Arch Dermatol Res) - "The SUCRA rank indicated that oral dexamethasone (95.9%) > diphenylcyclopropenone(DPCP) (74.5%) > oral ritlecitinib (62.6%) > oral baricitinib (46.9%) > squaric acid dibutyl ester(SADBE) (20.1%) > placebo (0.0%) from high to low in the aspect of improving efficacy. Some adverse events associated with oral dexamethasone and DPCP were intolerable to patients, whereas those related to oral ritlecitinib and oral baricitinib were more manageable. Overall, ritlecitinib and baricitinib remain promising drugs in the future treatment of severe AA."

Clinical • Journal • Retrospective data • Review • Alopecia • Immunology

Oral tofacitinib monotherapy for the management of moderate-to-severe alopecia areata in children and adolescents: a retrospective analysis of 36 cases (BAD 2024) - "Among those not showing a response, three patients each underwent a transition to combination therapy of oral steroids with methotrexate and topical immunotherapy with diphenylcyclopropenone. Limitations of the study include the retrospective nature and small sample size. This comprehensive analysis enriches the existing literature on the role of tofacitinib in paediatric AA, addressing gaps in approved treatments and providing valuable guidance for clinicians navigating the challenges of nonresponsiveness in this vulnerable population."

Monotherapy • Retrospective data • Alopecia • Immunology • Pediatrics

Oral tofacitinib monotherapy for the management of moderate-to-severe alopecia areata in children and adolescents: a retrospective analysis of 36 cases (BAD 2024) - "Among those not showing a response, three patients each underwent a transition to combination therapy of oral steroids with methotrexate and topical immunotherapy with diphenylcyclopropenone. Limitations of the study include the retrospective nature and small sample size. This comprehensive analysis enriches the existing literature on the role of tofacitinib in paediatric AA, addressing gaps in approved treatments and providing valuable guidance for clinicians navigating the challenges of nonresponsiveness in this vulnerable population."

Monotherapy • Retrospective data • Alopecia • Dermatology • Immunology • Pediatrics

Essential role of macrophages in contact hypersensitivity-induced hair regeneration. (PubMed, J Invest Dermatol) - No abstract available

Journal • Alopecia • Contact Dermatitis • Dermatitis • Dermatology • 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 2024 ➔ Jun 2025

Trial primary completion date • Dermatology

An overview of cyclopropenone derivatives as promising bioactive molecules. (PubMed, Bioorg Med Chem Lett) - "The cyclopropenone analogue diphenylcyclopropenone (DPCP) has been approved for the treatment of AA. Given the potential therapeutic benefits of cyclopropenone derivatives, this review aims to systematically summarize the structures, synthesis routes, and potential pharmacological functions of cyclopropenone analogues in the hope of offering novel insights for further rational design of more drugs based on the cyclopropenone skeleton for the treatment of human diseases."

Journal • Review • Alopecia • Breast Cancer • Immunology • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer

Astroglial Morphological Changes in Periaqueductal Grey in Different Pain and Itch Mice Models. (PubMed, Behav Brain Res) - "The findings showed that different pain and itching conditions have different astrocyte morphologies, and these variations in morphological changes help to explain the pathophysiology of these conditions."

Journal • Preclinical • Oncology • Osteosarcoma • Pain • Sarcoma • Solid Tumor • FAP • GFAP