| Identification | Back Directory | [Name]
VTX-2337 | [CAS]
926927-61-9 | [Synonyms]
VTX 378
CS-1536
VTX-2337
Motolimod
Obicetrapib
VTX 2337;VTX2337
Motolimod(VTX-2337)
VTX 2337;VTX2337;VTX-378
2-amino-n,n-dipropyl-8-[4-(pyrrolidine-1-carbonyl)phenyl]-3h-1-benzazepine-4-carboxamide
2-amino-N,N-dipropyl-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepine-4-carboxamide
3H-1-Benzazepine-4-carboxamide, 2-amino-N,N-dipropyl-8-[4-(1-pyrrolidinylcarbonyl)phenyl]- | [Molecular Formula]
C28H34N4O2 | [MDL Number]
MFCD28044318 | [MOL File]
926927-61-9.mol | [Molecular Weight]
458.6 |
| Chemical Properties | Back Directory | [Boiling point ]
718.7±70.0 °C(Predicted) | [density ]
1.19±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (up to at least 25 mg/ml) | [form ]
solid | [pka]
2.47±0.40(Predicted) | [color ]
Off-white or pale yellow | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. | [InChI]
1S/C28H34N4O2/c1-3-13-31(14-4-2)28(34)24-17-23-12-11-22(18-25(23)30-26(29)19-24)20-7-9-21(10-8-20)27(33)32-15-5-6-16-32/h7-12,17-19,30H,3-6,13-16,29H2,1-2H3 | [InChIKey]
CQAGPRVMJDWWEA-UHFFFAOYSA-N | [SMILES]
N4(CCCC4)C(=O)c1ccc(cc1)c2cc3c(cc2)C=C(C=C(N3)N)C(=O)N(CCC)CCC |
| Hazard Information | Back Directory | [Description]
Motolimod is an agonist of toll-like receptor 8 (TLR8).1 It increases the production of TNF-α and IL-12 in human peripheral blood mononuclear cells (PBMCs; EC50s = 140 and 120 nM, respectively), monocytes, and myeloid dendritic cells. Motolimod also increases IFN-γ production in natural killer (NK) cells and increases cytolysis in K562 NK cell-sensitive leukemia cells when used at concentrations of 167 and 500 nM for 48 hours. It increases plasma levels of a group of human cytokines, including IL-6, IL-12p70, TNF-α, MCP-1, and MIP-1β, in NOD-scid IL2rynull (NSG) mice reconstituted with human immune system (NSG-HIS) when administered at doses of 1.5 and 15 mg/m2.2 Motolimod, when used in combination with pegylated liposomal doxorubicin (PLD), reduces tumor growth and increases tumor infiltration of monocytes and T cells in an ovarian cancer NSG-HIS mouse model. | [Uses]
Motolimod is an agonist of toll-like receptor 8 (TLR8) with potential immune-stimulating and antineoplastic properties. Motolimod is used in combination with PLD for the treatment of ovarian cancer. | [in vivo]
Monkeys receive a subcutaneous injection of Motolimod (1 or 10 mg/kg), and plasma is collected predose, 6, 12, 24, and 96 h post-injection. For the 10 mg/kg dose, mean plasma levels of IL-1β increase from baseline levels of 0.5 pg/mL, up to 9.12±2.7 ng/mL (p<0.05, t-test) at 6 h post-administration of Motolimod (10 mg/kg). Circulating levels of IL-18 also increase from a baseline of ~ 1 pg/mL to 68.7±4.4 pg/mL (p<0.05, t-test) at 6 h in response to the Motolimod (VTX-2337) treatment (10 mg/kg). Levels of IL-6 are monitored, as this mediator is induced in response to TLR8 activation, but the release is independent of NLRP3 inflammasome activation. In addition, plasma levels of IFNγ are assessed as a measure of NK cell activation in response to Motolimod treatment[2]. | [IC 50]
TLR8 | [References]
1) Lu?et al.?(2012),?VTX-2337 is a Novel TLR8 Agonist That Activates NK Cells and Augments ADCC;?Clin. Cancer Res.?18?499
2) Lu?et al.?(2013),?TLR8 agonist VTX-2337 enhances NKG2D-mediated cytotoxicity of NK cells;?J. Immunother. Cancer?1?P44
3) Rutman?et al.?(2015),?Motolimod,a selective TLR8 agonist, induces apoptosis in monocytic myeloid-derived suppressor cells (M-MDSC);?J. Immunother. Cancer.?3?P296
4) Ferris?et al.?(2014),?Active8: a random, double-blind, placebo-controlled study of chemotherapy plus cetuximab in combination with TLR8 agonist VTX-2337 in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN);?J. Immunother. Cancer?2P69
5) Monk?et al.?(2017),?Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemo-Immunotherapy;?Clin. Cancer Res.?23?1955
6) Dietsch?et al.?(2016),?Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, Ignites Tumoricidal Natural Killer Cell Activity;?PLoS One?11?e0148764 |
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