Discovery of pyrrolo[2,3-d]pyrimidine-based molecules as a Wee1 inhibitor template.

In the past decade, Wee1 inhibition has received widespread attention as a cancer therapy. Our research aims to discover effective, selective and drug-like Wee1 inhibitors. Herein, a series of compounds with pyrrolo[2,3-d]pyrimidine-based heterocycles were designed, synthesized and confirmed to inhibit Wee1 kinase. The inhibitors afforded good potency in Wee1 Kinase inhibitory activity in enzymatic assays. These compounds showed strong proliferation inhibition against NCI-1299 cell lines and had acceptable pharmacokinetic properties. These derivatives are promising inhibitors that warrant further evaluation, towards the development of potential anticancer drug.

Efficacy and safety of hemoporfin photodynamic therapy for port-wine stains in paediatric patients: A retrospective study of 439 cases at a single centre.

BACKGROUND: Although hemoporfin photodynamic therapy is a promising treatment approach for port-wine stains, its efficacy in children has not been sufficiently assessed. We aimed to evaluate the efficacy and safety of this approach in a paediatric population. METHODS: We retrospectively analysed the medical records of 439 children with port-wine stains receiving hemoporfin photodynamic therapy at our institution from July 2017 to January 2020. They received intravenous hemoporfin (hematoporphyrin monomethyl ether, 5 mg/kg), followed by lesion irradiation with a 532-nm green LED light for 20-25 min. The stains' blanching degree and occurrence of adverse events were registered. RESULTS: Overall, 95.2% of patients showed an 'effective response' (>20% fading) and 74.3% showed almost-complete resolution and great improvement (≥60% fading). Red and pink lesions showed better response than purple lesions (P < 0.05). Neck and facial lesions showed better response than the trunk and extremity lesions (P < 0.05). The response of the patients to the PDT showed a cumulative effect of the treatment session. No photosensitivity or systemic adverse reactions were observed. Transient local adverse effects included swelling, purpura, crusts, and pigmentation, which resolved without treatment. Only 2% of children had permanent scars, likely related to scratching crusts. CONCLUSIONS: Hemoporfin photodynamic therapy was well tolerated and effective in paediatric Chinese patients with port-wine stains. It could be recommended as the first choice, over pulsed-dye laser therapy, for treating port-wine stains, particularly for large lesions. This should be evaluated in direct clinical trials.

A clinical study of HMME-PDT therapy in Chinese pediatric patients with port-wine stain.

OBJECTIVE: To report our observations from a trial of the effectiveness and safety of hematoporphyrin monomethyl ether photodynamic therapy (HMME-PDT) in treating Chinese Pediatric patients port-wine stains (PWS). METHOD: From October 2017 to December 2017, the study recruited 82 patients of PWS with negative HMME skin test results. The patients received an intravenous injection of 5 mg/kg HMME and the affected areas were exposed to 532 nm LED green light, with the irradiation power density between 80-85 mW/cm2. Each light spot was irradiated for 20-25 min. After two treatments, the clinical efficacy and posttreatment reactions at each treated area were observed. RESULT: The patient age between 1 and 14 years old. 24 of the 82 cases were cured (29.27%) after two HMME-PDT treatment, 34 cases indicates a good efficacy (41.46%), 16 cases showed alleviation (19.51%), while 8 cases displayed no efficacy (9.76%). Pain was observed during treatment, and post-treatment edema was observed at the treated areas. No other obvious systematic adverse reaction were reported. CONCLUSION: HMME-PDT is an effective and safe treatment for pediatric patients with PWS.