Sonidegib, also known as LDE225 and marketed as Odomzo, is a Hedgehog signaling pathway inhibitor (via smoothened antagonism) developed as an anticancer agent by Novartis. It was approved by the FDA for treating basal cell carcinoma in July 2015 and is awaiting approval in the EU. The hedgehog pathway is involved in many human cancers. Sonidegib effectively inhibits the regulator called smoothened (Smo), preventing the hedgehog pathway from functioning. As a result, tumours that depend on the hedgehog pathway are unable to grow. Sonidegib is approved for use in the US and EU for treatment of adults with locally advanced basal cell carcinoma (BCC) that has recurred post surgery or radiation therapy. It is also approved for adult patients with BCC who are not eligible for surgery or radiation therapy.

Vismodegib (trade name Erivedge) is a drug for the treatment of basal-cell carcinoma (BCC). It was approved by FDA on January 30, 2012 and by the European Commission on 12 July 2013, for the treatment of adult patients with symptomatic metastatic BCC, or locally advanced BCC inappropriate for surgery or radiotherapy. The drug is also undergoing clinical trials for metastatic colorectal cancer, small-cell lung cancer, advanced stomach cancer, pancreatic cancer, medulloblastoma and chondrosarcoma as of June 2011. The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the hedgehog signaling pathway. The Hedgehog signaling pathway plays an important role in tissue growth and repair; aberrant constitutive activation of Hedgehog pathway signaling and uncontrolled cellular proliferation may be associated with mutations in the Hedgehog-ligand cell surface receptors PTCH and SMO. SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway. This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.

Cycloheximide is an antibiotic produced by fermentation culture of Streptomyces griseus, Streptomyces noursei, Streptomyces albulus, Streptomyces naraensis, or other cycloheximide-producing microorganism. It was first discovered by A. Whiffen et al. in 1946. She observed the activity of the compound against the yeasts and it became known as the first antifungal antibiotic. Cycloheximide has been marketed as a plant fungicide for many years and this use continues mainly against fungal diseases of turf and for powdery mildew on roses. More recently, cycloheximide has been recognized and is being developed as an abscission agent for citrus fruits and olives. Due to significant toxic side effects, including DNA damage, teratogenesis, and other reproductive effects, cycloheximide is generally used only in in vitro research applications, and is not suitable for human use as a therapeutic compound. Cycloheximide is an antimitotic and an inhibitor of the synthesis of both DNA and protein.

CUR-61414 is a novel small molecule Hh inhibitor that can block elevated Hh signaling activity resulting from oncogenic mutations in Patched-1. CUR-61414 can suppress proliferation and induce apoptosis of basaloid nests in the BCC model systems, whereas having no effect on normal skin cells. Cur-61414 was successful in eradicating the basal cell carcinomas in mouse ex-vivo model but failed in phase I trials in humans as it could not penetrate the human skin.

Solasonine, a known glycoalkaloid, is a potential anti-cancer agent. Solasonine is a component of Curaderm BEC5 indicated for the topical treatment of actinic keratosis, keratoacanthoma, basal cell carcinoma and cutaneous superficial squamous cell carcinoma. BEC is a standardized mixture of Solamargine (33%), Solasonine (33%) and di-and monoglycosides of solasodine (34%) extracted from S. sodomaeum, now reclassified as S. linnaeanum. Solasonine could inhibit cell proliferation, migration and colony formation of glioma cells. Treatment of solasonine induced apoptosis via modulating cytochrome c and caspase signaling. Besides, solasonine decreased the expression of proinflammatory mediators and nuclear translocalization of NF-κB p50/p65. Mechanistic investigation further revealed that solasonine may target anti-inflammatory signaling pathway, and more specifically p-p38 and p-JNK MAPKs.

Sonidegib, also known as LDE225 and marketed as Odomzo, is a Hedgehog signaling pathway inhibitor (via smoothened antagonism) developed as an anticancer agent by Novartis. It was approved by the FDA for treating basal cell carcinoma in July 2015 and is awaiting approval in the EU. The hedgehog pathway is involved in many human cancers. Sonidegib effectively inhibits the regulator called smoothened (Smo), preventing the hedgehog pathway from functioning. As a result, tumours that depend on the hedgehog pathway are unable to grow. Sonidegib is approved for use in the US and EU for treatment of adults with locally advanced basal cell carcinoma (BCC) that has recurred post surgery or radiation therapy. It is also approved for adult patients with BCC who are not eligible for surgery or radiation therapy.