UK-383367 / Pfizer - LARVOL DELTA

Multiomics Mendelian Randomization of GWAS, eQTL, and pQTL Combined With Drug Analysis to Predict Drug Targets in Myocardial Infarction. (PubMed, J Cardiovasc Pharmacol Ther) - "While BMP1 is traditionally associated with extracellular matrix remodeling, this study provides the first genetic evidence establishing it as an independent causal risk factor for MI, distinct from conventional traits such as hypertension. By bridging causal genetic inference with structure-based drug prediction, we propose BMP1 inhibition, specifically via agents like UK-383367, as a promising therapeutic strategy to mitigate MI-related pathological remodeling."

Journal • Cardiovascular • Hypertension • Myocardial Infarction • ALDH2 • APOB

Intestinal Epithelial-like Cells Stimulated by a Functional Food Ingredient Promote Lysyl Oxidase (LOX) Expression in Osteoblast Precursor Cells via BMP-1 Secretion. (PubMed, Int J Mol Sci) - "LOX mRNA expression and total LOX activity were increased in MG63 cells treated with the conditioned supernatant, and inhibition of BMP-1/procollagen C-proteinase activity (UK383367) attenuated LOX mRNA induction. Collectively, these results suggest that L. brevis AS-1 stimulates intestinal epithelial-like cells to secrete BMP-1, which in turn promotes LOX mRNA expression in osteoblast precursor cells. This in vitro mechanism supports the concept of gut-bone crosstalk regulating molecular factors associated with bone quality."

Journal • Osteoporosis • Rheumatology • LOX • TGFB1

BMP1 Appears to be Involved in GPER1-mediated Progression and Tamoxifen Resistance of Luminal A Breast Cancer Cells. (PubMed, Cancer Genomics Proteomics) - "BMP1 appears to be involved in GPER1-mediated progression of luminal A breast cancer cells. In addition, BMP1 may play a role in tamoxifen-resistance."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • GPER1

BMP-1 inhibition modulates tumor growth and cytokine responses in combination with doxorubicin in a mouse model of metastatic breast cancer (CICON 2025) - "This study was supported by TÜBİTAK 122Z177. Keywords: Breast cancer, BMP-1, UK-383367, Doxorubicin, cytokines"

Combination therapy • Metastases • Preclinical • Breast Cancer • Oncology • Solid Tumor • IFNG • IL10 • IL6 • TNFA

BMP1 inhibitor UK383367 improves MI-induced cardiac remodeling and fibrosis in mice via ameliorating macrophage polarization and mitochondrial dysfunction. (PubMed, Acta Pharmacol Sin) - "Overall, these results reveal a pivotal yet detrimental role for BMP1 in driving myocardial fibrosis and amplifying inflammatory cascades after MI. This study highlights the therapeutic potential of the BMP1 inhibitor UK383367 as a promising alternative to conventional antifibrotic strategies, potentially curbing the progression toward HF."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Inflammation • Metabolic Disorders • Myocardial Infarction • IL6 • TNFA

Poldip2 mediates blood-brain barrier disruption and cerebral edema by inducing AQP4 polarity loss in mouse bacterial meningitis model. (PubMed, CNS Neurosci Ther) - "Poldip2 inhibition alleviated brain edema and preserved the integrity of BBB partially by relieving the loss of AQP4 polarity via MMPs/β-DG pathway."

Journal • Preclinical • Cardiovascular • CNS Disorders • Infectious Disease • Ischemic stroke • Glial Fibrillary Acidic Protein • POLD1

Inhibitors of BMP-1/tolloid-like proteinases: efficacy, selectivity and cellular toxicity. (PubMed, FEBS Open Bio) - "...As a first step towards the identification of suitable tools to be used in functional studies, we have undertaken a systematic comparison of seven molecules known to affect the proteolytic activity of human astacins including three hydroxamates (FG-2575, UK383,367, S33A), the protein sizzled, a new phosphinic inhibitor (RXP-1001) and broad-spectrum protease inhibitors (GM6001, actinonin)...We found that these molecules display very different potency and selectivity profiles, with hydroxamate FG-2575 and the protein sizzled being very powerful and selective inhibitors of BMP-1, whereas phosphinic peptide RXP-1001 behaves as a broad-spectrum inhibitor of astacins. Their use should therefore be carefully considered in agreement with the aim of the study to avoid result misinterpretation."

Clinical • Journal • Biosimilar • Oncology • Ophthalmology

BMP1 inhibitor UK-383,367 attenuates renal fibrosis and inflammation in CKD. (PubMed, Am J Physiol Renal Physiol) - "In vitro, UK383,367 pretreatment inhibited the induction of collagen I/III, fibronectin, and α-SMA in both mPTCs and NRK-49F cells treated with TGF-β1. Taken together, these findings indicated that BMP1 inhibitor UK383,367 could serve as a potential drug in antagonizing CKD renal fibrosis by acting on the maturation and deposition of collagen and subsequent profibrotic response and inflammation."

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Bone morphogenetic protein 1 cleaves the linker region between ligand-binding repeats 4 and 5 of the LDL receptor and makes the LDL receptor non-functional. (PubMed, Hum Mol Genet) - "This conclusion is based upon the use of the specific BMP1 inhibitor UK 383367, silencing of the BMP1 gene by the use of siRNA or CRISPR/Cas9 technology and overexpression of wild-type BMP1 or the loss-of-function mutant E214A-BMP1...Targeting BMP1 could represent a novel strategy to increase the number of functioning LDLRs in order to lower plasma LDL cholesterol levels. However, a concern by using BMP1 inhibitors as cholesterol-lowering drugs, could be the risk of side-effects due to the important role of BMP1 in collagen assembly."

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