N-Cyclopropyl-(20R)-2-Methylene-19,26,27-trinor-25-aza-Vitamin D analogs and their uses

This invention discloses N-cyclopropyl-(20R)-2-methylene-19,26,27-trinor-25-aza-vitamin D analogs, and specifically N-cyclopropyl-(20R)-2-methylene-19,26,27-trinor-25-aza-1.alpha.-hydroxyvi- tamin D.sub.3 and pharmaceutical uses therefor. This compound exhibits relatively high binding activity and pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent especially for the treatment or prevention of leukemia, colon cancer, breast cancer, skin cancer or prostate cancer

2alpha-Methyl and 2beta-Methyl Analogs of 19,26-Dinor-1alpha,25-Dihydroxyvitamin D3 and Their Uses

This invention discloses 2.alpha.-methyl and 2.beta.-methyl analogs of 19,26-dinor-1.alpha.,25-dihydroxyvitamin D.sub.3 and pharmaceutical uses therefor. These compounds exhibit in vitro biological activities evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. These compounds have little, if any, in vivo calcemic activity and therefore may be used to treat autoimmune disorders in humans as well as secondary hyperparathyroidism and renal osteodystrophy

Highlights from the 24th workshop on vitamin D in Austin, September 2022

The 24th Workshop on Vitamin D was held September 7-9, 2022 in Austin, Texas and covered a wide diversity of research in the vitamin D field from across the globe. Here, we summarize the meeting, individual sessions, awards and presentations given

Vitamin D deficiency in the ApcPirc/+ rat does not exacerbate colonic tumorigenesis, while low dietary calcium might be protective

Human studies have shown that individuals with colon cancer tend to have lower serum 25-hydroxy-vitamin D3 [25(OH)D3] levels compared with healthy controls, but whether this link is causative, a result of the disease or an indicator of another factor altogether has yet to be demonstrated. In humans, vitamin D, calcium and UV exposure are inextricably linked; therefore, understanding the individual and combined roles of each of these will require animal models specifically designed to address these questions. To begin to untangle this network, our group has employed the ApcPirc/+ rat, which contains a truncating mutation in the Apc gene, leading to the development of colonic tumors. Our group previously utilized this model to demonstrate that vitamin D supplementation above normal does not reduce colonic tumor burden and, in fact, increased tumor multiplicity in a dose-dependent manner. In the current study, we tested whether vitamin D deficiency plays a causative role in tumor development using two strains which differ in their susceptibility to intestinal tumorigenesis. In the colon, vitamin D deficiency did not increase the development of tumors in either strain, and was actually protective in one strain. Unexpectedly, low dietary calcium combined with vitamin D deficiency significantly suppressed tumor development in the small intestine and colon of both strains. The vast majority of tumors in the human intestine occur in the colon, and we find no evidence to support a direct role of vitamin D deficiency in increasing colonic tumorigenesis, and low calcium might protect against tumor development. This article has an associated First Person interview with the first author of the paper

2-methylene-19,26-dinor-(20S,22E,25R)-vitamin D analogs

This invention discloses 2-methylene-19,26-dinor-(20S,22E,25R)-vitamin D analogs, and specifically 2-methylene-19,26-dinor-(20S,22E,25R)-1.alpha.,25-dihydroxyvitamin D.sub.3, and pharmaceutical uses therefor. This compound exhibits transcription activity as well as pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. This compound also shows no activity in vivo on bone calcium mobilization and relatively low intestinal calcium transport activity compared to the native hormone 1.alpha.,25-dihydroxyvitamin D.sub.3, and therefore may be used to treat autoimmune disorders or inflammatory diseases in humans as well as renal osteodystrophy. This compound may also be used for the treatment or prevention of obesity