Motolimod - CAS 926927-61-9
Catalog number: B0084-462238
Category: Inhibitor
Not Intended for Therapeutic Use. For research use only.
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Molecular Weight:
Toll-like Receptor (TLR)
A small-molecule agonist of TLR8, with potential immunostimulating and antineoplastic activities
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B0084-462238 100 mg $199 In stock
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Brife Description:
A small-molecule agonist of TLR8, with potential immunostimulating and antineoplastic activities
Solid powder
VTX-2337; VTX-378; 2-amino-N,N-dipropyl-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepine-4-carboxamide
10 mM in DMSO
Please store the product under the recommended conditions in the Certificate of Analysis.
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1.Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, Ignites Tumoricidal Natural Killer Cell Activity.
Dietsch GN1, Lu H2, Yang Y2, Morishima C2,3, Chow LQ4, Disis ML2, Hershberg RM1. PLoS One. 2016 Feb 29;11(2):e0148764. doi: 10.1371/journal.pone.0148764. eCollection 2016.
VTX-2337 (USAN: motolimod) is a selective toll-like receptor 8 (TLR8) agonist, which is in clinical development as an immunotherapy for multiple oncology indications, including squamous cell carcinoma of the head and neck (SCCHN). Activation of TLR8 enhances natural killer cell activation, increases antibody-dependent cell-mediated cytotoxicity, and induces Th1 polarizing cytokines. Here, we show that VTX-2337 stimulates the release of mature IL-1β and IL-18 from monocytic cells through coordinated actions on both TLR8 and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome complex. In vitro, VTX-2337 primed monocytic cells to produce pro-IL-1β, pro-IL-18, and caspase-1, and also activated the NLRP3 inflammasome, thereby mediating the release of mature IL-1β family cytokines. Inhibition of caspase-1 blocked VTX-2337-mediated NLRP3 inflammasome activation, but had little impact on production of other TLR8-induced mediators such as TNFα.
2.VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC.
Lu H1, Dietsch GN, Matthews MA, Yang Y, Ghanekar S, Inokuma M, Suni M, Maino VC, Henderson KE, Howbert JJ, Disis ML, Hershberg RM. Clin Cancer Res. 2012 Jan 15;18(2):499-509. doi: 10.1158/1078-0432.CCR-11-1625. Epub 2011 Nov 29.
PURPOSE: We aim to characterize VTX-2337, a novel Toll-like receptor (TLR) 8 agonist in clinical development, and investigate its potential to improve monoclonal antibody-based immunotherapy that includes the activation of natural killer (NK) cells.
3.A phase I dose-finding study of the novel Toll-like receptor 8 agonist VTX-2337 in adult subjects with advanced solid tumors or lymphoma.
Northfelt DW1, Ramanathan RK2, Cohen PA1, Von Hoff DD3, Weiss GJ2, Dietsch GN4, Manjarrez KL4, Randall TD4, Hershberg RM5. Clin Cancer Res. 2014 Jul 15;20(14):3683-91. doi: 10.1158/1078-0432.CCR-14-0392. Epub 2014 May 7.
PURPOSE: This phase I, open-label, uncontrolled, ascending-dose study explored the safety, maximum tolerated dose (MTD), pharmacokinetics, and pharmacology of the TLR8 agonist VTX-2337 in subjects with advanced solid tumors or lymphoma.
4.Late-Stage Cancer Patients Remain Highly Responsive to Immune Activation by the Selective TLR8 Agonist Motolimod (VTX-2337).
Dietsch GN1, Randall TD2, Gottardo R3, Northfelt DW4, Ramanathan RK5, Cohen PA4, Manjarrez KL2, Newkirk M2, Bryan JK2, Hershberg RM2. Clin Cancer Res. 2015 Dec 15;21(24):5445-52. doi: 10.1158/1078-0432.CCR-15-0578. Epub 2015 Jul 7.
PURPOSE: Immunotherapy as a treatment for cancer holds the promise of complete and durable tumor remission, yet the immunosuppressive environment created by many tumors, advanced patient age, and previous treatments with cytotoxic agents may limit the approach. The activity of motolimod (VTX-2337), a potent and selective Toll-like receptor 8 (TLR8) agonist, was therefore assessed in the context of advanced, late-stage cancer patients.
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