THR-184 / Thrasos Therap - LARVOL DELTA

A Process for the Design and Development of Novel Bone Morphogenetic Protein-7 (BMP-7) Mimetics With an Example: THR-184. (PubMed, Front Pharmacol) - "THR-184 has progressed through phase I and II clinical trials for the prevention of Cardio-Vascular Surgery (CVS) associated AKI. This work provides a roadmap for the development of other growth factor mimetics and demonstrates how we might harness their therapeutic potential."

Journal • Acute Kidney Injury • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • Reperfusion Injury

Molecular determinants for agonist recognition and discrimination in P2X2 receptors. (PubMed, J Gen Physiol) - "Our findings demonstrate that while the Lys69 backbone carbonyl makes an important contribution to ligand recognition, the discrimination between different ligands is mediated by both the side chain and the backbone carbonyl oxygen of Thr184. Together, our data demonstrate how conserved elements in P2X2Rs recognize and discriminate agonists."

Journal • Cognitive Disorders • Immunology • Pain

The protein level and transcription activity of activating transcription factor 1 is regulated by prolyl isomerase Pin1 in nasopharyngeal carcinoma progression. (PubMed) - "The ATF1 promoted NPC tumorigenesis was regulated by Pin1 both in vitro and in vivo. All these findings clearly state that Pin1 is a novel regulator of ATF1 at Thr184 and thereby enhances ATF1 transcription activity and tumorigenesis promotive function in NPC."

Journal • Biosimilar • Oncology • Solid Tumor

A Study of THR-184 in Patients at Risk of Developing Cardiac Surgery Associated-Acute Kidney Injury (CSA-AKI) (clinicaltrials.gov) - P2; N=450; Recruiting; Sponsor: Thrasos Innovation, Inc.; N=350 -> 450 ; Trial primary completion date: Dec 2014 ->Oct 2015

Enrollment change • Trial primary completion date • Acute Kidney Injury • Biosimilar • Chronic Kidney Disease • Dyslipidemia • Renal Disease

Understanding the Hsp90 N-terminal Dynamics: Structural and Molecular Insights into the Therapeutic Activities of Anticancer Inhibitors Radicicol (RD) and Radicicol Derivative (NVP-YUA922). (PubMed, Molecules) - "Radicicol (RD) and its derivative, resorcinylic isoxazole amine NVP-AUY922 (NVP), have shown promising pharmacodynamics against Hsp90 activity. The key residues influential in this interaction are Gly 97, Asp 93 and Thr 184. These findings provide valuable insights into the Hsp90 dynamics and will serve as a guide for the design of potent novel inhibitors for cancer treatment."

Journal • Oncology • HSP90AA1

Natural compounds as potential Hsp90 inhibitors for breast cancer-Pharmacophore guided molecular modelling studies. (PubMed, Comput Biol Chem) - "In the present in silico investigation, a structure-based pharmacophore model was generated with hydrogen bond donor, hydrogen bond acceptor and hydrophobic features complementary to crucial residues Ala55, Lys58, Asp93, Ile96, Met98 and Thr184 directed at inhibiting the ATP-binding activity of Hsp90...The reference and hit compounds with dock scores of 48.27 (Geldanamycin), 40.90 (Radicicol), 73.04 (Hit1), 72.92 (Hit2) and 68.12 (Hit3) were further validated for their binding stability through molecular dynamics simulations. We propose that the non-macrocyclic scaffolds of three identified phytochemicals might aid in the development of novel therapeutic candidates against Hsp90-driven cancers."

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Perioperative THR-184 and AKI after Cardiac Surgery. (PubMed, J Am Soc Nephrol) - "Safety-related outcomes were similar across all treatment groups. In conclusion, compared with placebo, administration of perioperative THR-184 through a range of dose exposures failed to reduce the incidence, severity, or duration of AKI after cardiac surgery in high-risk patients."

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Acute kidney injury: emerging pharmacotherapies in current clinical trials. (PubMed, Pediatr Nephrol) - "Here we review emerging pharmacotherapies for AKI that are currently in clinical trials. Categorized by their general mechanism of action, the therapies discussed include anti-inflammatory agents (recAP, AB103, ABT-719), antioxidants (iron chelators, heme arginate), vasodilators (levosimendan), apoptosis inhibitors (QPI-1002), and repair agents (THR-184, BB-3, mesenchymal stem cells)."

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