efatutazone (CS-7017) / Daiichi Sankyo - LARVOL DELTA

Thiazolidinedione derivatives in cancer therapy: exploring novel mechanisms, therapeutic potentials, and future horizons in oncology. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "As the oncology landscape evolves, TZD derivatives (rosiglitazone, pioglitazone, inolitazone, troglitazone, and 2,4-thiazolidinedione derivatives) represent a promising class of agents with the potential to contribute meaningfully to cancer treatment. By integrating existing knowledge with recent advancements, this study provides valuable insights into the role of thiazolidinedione derivatives in cancer treatment, paving the way for further research and clinical applications."

Journal • Review • Metabolic Disorders • Oncology • PPARG

Efficacy of Immediate Antihypertensive Treatment in Patients With Acute Ischemic Stroke With Different Blood Pressure Genetic Variants. (PubMed, Hypertension) - P=N/A | "Five BP-associated single nucleotide polymorphisms (rs16849225, rs17030613, rs1173766, rs6825911, and rs35444 in FIGN-GRB14, ST7L-CAPZA1, NPR3, ENPEP, and near TBX3, respectively) were genotyped among 2590 patients...Early antihypertensive treatment had a neutral effect on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072."

Journal • Cardiovascular • Ischemic stroke • NPR3 • TBX3

Efatutazone Dihydrochloride in Treating Patients With Previously Treated Myxoid Liposarcoma That Cannot Be Removed by Surgery (clinicaltrials.gov) - P2 | N=15 | Completed | Sponsor: Alliance for Clinical Trials in Oncology | Active, not recruiting ➔ Completed

Surgery • Trial completion • Liposarcoma • Oncology • Sarcoma • Solid Tumor • DDIT3

Inolitazone Dihydrochloride and Paclitaxel in Treating Patients With Advanced Anaplastic Thyroid Cancer (clinicaltrials.gov) - P2 | N=19 | Completed | Sponsor: Alliance for Clinical Trials in Oncology | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Trial completion • Breast Cancer • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma

In-silico discovery of inhibitors against human papillomavirus E1 protein. (PubMed, J Biomol Struct Dyn) - "The binding free energies for Cinalukast, Lobeglitazone, and Efatutazone were -37.84 kcal/mol, -25.30 kcal/mol, and -29.89 kcal/mol respectively. Therefore, we propose their chemical scaffolds for future rational design of E1 inhibitors.Communicated by Ramaswamy H. Sarma."

Journal • Cervical Cancer • Infectious Disease • Oncology • Solid Tumor

Surprising discoveries while using deuterium to stabilize enantiomers for chiral switching (ACS-Sp 2022) - "Below are highlights of the effects observed with several racemic compounds including pioglitazone, mitoglitazone, inolitazone, prasugrel, donepezil, lenalidomide, avadomide, iberdomide, and bupropion.Stabilization with deuterium may vary:- by compound even within the same compound class (e.g., thiazolidinediones); and- as a function of stereochemistry (sometimes there is no stabilization for one of the enantiomers).To date, the effects observed when deuterium is used to stabilize enantiomers include:1...Reduced rates of degradation – in addition to reduced enantiomerization (e.g., degradation of thalidomide analogs varies from none to 4x).3...Stereoselective formation of one protonated enantiomer versus the other due to different reaction kinetics (e.g. d-R forms predominately h-R vs h-S).5. Sometimes limited predictive value for in vivo effects of in vitro D/H exchange and enantiomerization studies."

Recent advances in the management of anaplastic thyroid cancer. (PubMed, Thyroid Res) - "Surgery should be as complete as possible, securing the airway and ensuring access for nutritional support; the current standard of care of radiotherapy is the intensity-modulated radiation therapy; chemotherapy includes the use of doxorubicin or taxanes (paclitaxel or docetaxel) generally with platin (cisplatin or carboplatin)...These include multitarget tyrosine kinase inhibitors (Lenvatinib, Sorafenib, Sunitinib, Vandetanib, Axitinib, Pazopanib, Pyrazolo-pyrimidine compounds), single target tyrosine kinase inhibitors (Dabrafenib plus Trametinib and Vemurafenib against BRAF, Gefitinib against EGFR, PPARγ ligands (e.g. Efatutazone), Everolimus against mTOR, vascular disruptors (e.g. Fosbretabulin), and immunotherapy (e.g. Spartalizumab and Pembrolizumab, which are anti PD-1/PD-L1 molecules)...Other single target mutation agents with fair results are Everolimus when a mutation involving the PI3K/mTOR pathway is detected, Imatinib in case of PDGF-receptors overexpression,..."

IO biomarker • Journal • Review • Immune Modulation • Inflammation • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF • EGFR

An AIB1 isoform alters enhancer access and enables progression of early stage triple-negative breast cancer. (PubMed, Cancer Res) - "Cellular crosstalk was inhibited by the PPARγ agonist efatutazone but was enhanced by treatment with the GR agonist dexamethasone. In conclusion, expression of the AIB1Δ4-selective cistrome in a small subpopulation of cells triggers an "enabler" phenotype hallmarked by an invasive transcriptional program and collective malignant progression in a heterogeneous tumor population."

Journal • Breast Cancer • Inflammation • Oncology • Solid Tumor • Triple Negative Breast Cancer • ANIB1

Vitamin D Status in Russian Children and Adolescents: Contribution of Genetic and Exogenous Factors. (PubMed, Front Pediatr) - "We studied the polymorphic variants c.1075A>C (I359L, rs1057910, CYP2C93) and c.430C>T (R144C, rs1799853, CYP2C92) in the CYP2C9 gene, c.1334T>C (M445T, rs4986910, CYP3A43), and CYP3A41B (c.-392C>T, rs2740574) in the CYP3A4 gene, 1846G>A, (rs3892097, CYP2D64) in the CYP2D6gene, TaqI (NM_000376.2: c.1056T>C; rs731236), FokI (NM_000376.2:c.2T>C; (rs2228570), and BsmI (NM_000376.2: c.1024+283G>A; rs1544410) in the VDR gene... Exogenous factors (time of year, place of residence, and prophylactic administration of cholecalciferol), as well as endogenous factors (age and sex), play a determining role in the development of vitamin D deficiency and insufficiency; in contrast to genetic factors-polymorphic variants of the genes of xenobiotic phase 1 enzymes (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and the VDR gene-which do not play such role. This study shows the need to create a diagnostic algorithm for Vitamin D deficiency based on the age, season of the..."

Clinical • Journal • CYP2C19 • CYP2C9 • CYP3A4 • DHCR7

Single nucleotide vitamin D receptor polymorphisms (FokI, BsmI, ApaI, and TaqI) in the pathogenesis of prematurity complications. (PubMed, Sci Rep) - "In 114 premature infants (< 32 weeks gestation) we analyze four single nucleotide VDR polymorphisms (rs2228570 (FokI), rs1544410 (BsmI), rs797532 (ApaI), rs731236 (TaqI)) for their association with respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP)...The ApaI VDR polymorphism appears to influence incidence of BPD and NEC in preterm infants. Considering VDR polymorphisms in future genetic investigations, in preterm complications, may prove clinically relevant."

Journal • Acute Respiratory Distress Syndrome • Bronchopulmonary Dysplasia • Gastrointestinal Disorder • Hematological Disorders • Respiratory Diseases • Retinal Disorders • Retinopathy of Prematurity

The Correlation Between Vitamin D Receptor (VDR) Gene Polymorphisms and Autism: A Meta-analysis. (PubMed, J Mol Neurosci) - "No significant differences were found in the allele frequencies of rs11568820, rs1544410, and rs2228570 in the cases and controls. This meta-analysis revealed that both VDR rs731236 and rs7975232 were significantly associated with autism, whereas VDR rs11568820, rs1544410, and rs2228570 might not be correlated with the incidence of autism."

Journal • Retrospective data • Autism Spectrum Disorder • Genetic Disorders

[VIRTUAL] Genetic Variation Associated With Favorable Exercise Response in Patients With Systolic Heart Failure: A Hf-action Trial Substudy (AHA 2020) - "The two most significantly associated loci across both additive and dominant meta-analysis models were rs111577308 located in the histone acetylation for transcription elongator complex 3 gene (ELP3, p=1.212x10-9) and rs75444785 located in the phosphodiesterase 4D gene (PDE4D, p=1.565x10-9)...Conclusions. Using a genome-wide association study in a well-phenotyped clinical trial of exercise in systolic heart failure, we found common genetic variants in genes involved in DNA transcription histone modification and cyclic AMP cell signaling that are associated with a more favorable response to exercise."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Peripheral Arterial Disease

Vitamin D Receptor Gene Polymorphisms and Cigarette Smoking Impact on Oral Health: A Case-Control Study. (PubMed, Int J Environ Res Public Health) - "The aim of the study was to analyze three SNPs in vitamin D receptor gene-rs7975232 (ApaI), rs2228570 (FokI) and rs1544410 (BsmI)-combined with oral health assessment-pH, gingival index, dry mouth, periodontitis, dry socket, redness of oral cavity mucosa, leukoplakia-in a group of cigarette smokers and in non-smokers...However, the impact of genetic variants, and also the impact of their interaction with smoking on analyzed parameters was also visible. These results show great possibilities for all levels of prevention of oral diseases by means of education based on evidence-based medicine, but also for incorporating genetic testing and early interventions into this process for predisposed individuals."

Clinical • Journal • Dental Disorders • Periodontitis • Xerostomia

Vitamin D Receptor Gene Polymorphisms Are Associated With Leprosy in Southern Brazil. (PubMed, Front Immunol) - "Some polymorphisms of the VDR gene, such as BsmI (G>A rs1544410), ApaI (G>T rs7975232), and TaqI (T>C rs731236) could affect its stability and mRNA transcription activity, while FokI T>C (rs2228570) gives a truncated protein with three fewer amino acids and more efficiency in binding vitamin D. This study evaluated these four polymorphisms in the immunopathogenesis of leprosy in 404 patients and 432 control individuals without chronic or infectious disease in southern Brazil...In individuals aged 40 or more years, this haplotype has also showed protection against leprosy per se and multibacillary (OR = 0.26, CI = 0.09-0.76; OR = 0.26, CI = 0.07-0.78, respectively), while the BAt haplotype was a risk factor for leprosy per se in the same age group (OR = 1.34, CI = 1.04-1.73). In conclusion, despite having found no associations between the VDR gene polymorphisms with the development of leprosy, the haplotypes formed by the BsmI, ApaI, and TaqI polymorphisms..."

Journal • Infectious Disease

Vitamin D receptor polymorphisms are associated with severity of wheezing illnesses and asthma exacerbations in children. (PubMed, J Steroid Biochem Mol Biol) - "We successfully genotyped five SNPs of the VDR gene (rs2525046, rs9729, rs1544410 (BsmI), rs22239179, and rs2228570 (FokI)) in 657 children presenting to a tertiary children's hospital with acute asthma, bronchiolitis, or a wheezing illness...No associations were identified between rs9729, rs2525046 and r2239179 polymorphisms and acute wheezing/asthma variables. These findings suggest that genetic variants at the VDR locus may play a role in acute wheeze/asthma severity in children."

Clinical • Journal • Asthma • Respiratory Diseases

Association of BsmI variant of vitamin D receptor gene with polycystic ovary syndrome: A case-control study. (PubMed, Int J Reprod Biomed) - "This study indicates no association between the BsmI genotypes and metabolic parameters. It can be concluded that VDR BsmI (rs1544410) Intron 8 (A G) was not associated with obesity along with PCOS susceptibility in the studied groups."

Clinical • Journal • Endocrine Disorders • Genetic Disorders • Obesity • Polycystic Ovary Syndrome • Women's Health • PCR

Study of CS-7017 in Colorectal Cancer Patients Who Have Achieved Disease Control Following First-Line Chemotherapy (clinicaltrials.gov) - P2; N=84; Terminated; Sponsor: Daiichi Sankyo, Inc.; Completed ➔ Terminated; Due to changes to the standard of care within the proposed market for CS-7017.

Clinical • Trial termination • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Association of genetic variations in the vitamin D pathway with susceptibility to tuberculosis in Kazakhstan. (PubMed, Mol Biol Rep) - "These genes play a number of different roles including synthesis, activation, delivery and binding of the activated vitamin D. Our preliminary results indicate significant association of VDR (vitamin D receptor) SNPs (rs1544410, BsmI, with OR = 0.425, CI 0.221-0.816, p = 0.009 and rs731236, TaqI with OR = 0.443, CI 0.228-0.859, p = 0.015) and CYP24A1 (rs6013897 with OR = 0.436, CI 0.191-0.996, p = 0.045) with TB. Interaction of genetic variation of VDR and CYP24A1 may impact susceptibility to TB. The findings provided initial clues to understand individual genetic differences in relation to susceptibility and protection to TB."

Journal • Infectious Disease • Tuberculosis

The association between vitamin D receptor gene polymorphism and susceptibility to hypertension: a meta-analysis. (PubMed, Eur Rev Med Pharmacol Sci) - "VDR BsmI gene polymorphism is closely related to the susceptibility to hypertension."

Journal • Retrospective data • Hypertension

Association between polymorphisms in the vitamin D receptor and susceptibility to multiple sclerosis. (PubMed, Pharmacogenet Genomics) - "The VDR FokI (rs2228570) polymorphism was significantly associated with developing MS. We found no influence of the ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms on the risk of developing MS in our patients."

Journal • CNS Disorders • Multiple Sclerosis • CDX-2

Association of vitamin D genetic pathway with asthma susceptibility in the Kurdish population. (PubMed, J Clin Lab Anal) - "In summary, our results explain the influence of the genetic variations in VDR and VDBP in addition to Vit D and VDBP serum concentrations on asthma susceptibility in the Kurdish population."

Clinical • Journal • Asthma • Respiratory Diseases

Vitamin D receptor polymorphisms in spontaneous preterm birth: a case-control study. (PubMed, Croat Med J) - "The TT genotype of the VDR FokI polymorphism is associated with newborn birth weight in women of European origin with SPTB."

Clinical • Journal • Gynecology • Obstetrics

BsmI-ApaI-TaqI TAC (BAt) Haplotype of Vitamin D Receptor Gene Is Associated with Increased Risk of Major Depressive Disorder. (PubMed, J Mol Neurosci) - "Although the VDR gene has been well characterized and a vast number of polymorphisms have been identified, the association between BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) single-nucleotide polymorphisms (SNPs), together with their haplotypes, and MDD risk have yet to be established...However, the TAC (BAt) haplotype was associated with increased odds of MDD (adjusted OR = 2.17, 95% CI = 1.30-3.61, p = 0.003) using CCT (baT) as reference haplotype. The findings suggest that the BsmI-ApaI-TaqI TAC (BAt) haplotype of the VDR gene increases susceptibility to MDD."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Vitamin D and its receptor polymorphisms are associated with glaucoma. (PubMed, J Fr Ophtalmol) - "This meta-analysis suggests that patients with glaucoma may have vitamin D deficiency. In addition, the vitamin D signalling cascade may be a contributing factor in developing glaucoma, which is supported by the evidence that b allele carriers of VDR BsmI exhibited an increase in the risk of glaucoma. Thus, dietary supplementation of vitamin D may become an important approach as an additional treatment for glaucoma."

Journal • Glaucoma • Ophthalmology

Vitamin D receptor gene polymorphisms are associated with psoriasis susceptibility and the clinical response to calcipotriol in psoriatic patients. (PubMed, Exp Dermatol) - "A total of 110 patients and 183 controls were genotyped for VDR gene polymorphisms rs2228570, rs731236, rs1544410 and rs7975232 by LDR method...Among the patients with PASI<3, the response rates to calcipotriol were significantly higher in patients with rs7975232 CC genotypes than in those with other genotypes (x =9.172, P=0.010). These data suggest that VDR polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients."

Clinical • Journal • Dermatology • Immunology • Psoriasis