| CAS |
No.926927-61-9 |
| 英文名称 |
Motolimod |
| 分子式 |
C28H34N4O2 |
| 分子量 |
458.6 |
| 溶解性 |
Soluble in DMSO ≥5mg/mL |
| 纯度 |
≥98% |
| 外观(性状) |
Solid |
| 储存条件 |
Powder:-20℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD28044318 |
| SMILES |
CCCN(CCC)C(=O)C1=CC2=C(C=C(C=C2)C3=CC=C(C=C3)C(=O)N4CCCC4)N=C(C1)N |
| InChIKey |
QSPOQCXMGPDIHI-UHFFFAOYSA-N |
| InChI |
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/h7-12，17-18H，3-6，13-16，19H2，1-2H3，(H2，29，30) |
| PubChem CID |
16049404 |
| 靶点 |
Toll-like Receptor (TLR) |
| 通路 |
Immunology & Inflammation |
| 背景说明 |
是一种选择性且有效的Toll-like receptor 8 (TLR8)激动剂。 |
| 生物活性 |
Motolimod (VTX-2337;VTX-378) is a selective Toll-like receptor 8 (TLR8) agonist， with an EC50 of approximately 100 nM.[1-2] |
| In Vitro |
在测试的 TLR (TLR2、3、4、5、7、8 和 9) 中，Motolimod (VTX-2337) 选择性激活 TLR8。Motolimod 刺激 PBMC 中 TNFα (EC50=140±30 nM，基于 10 个供体) 和 IL-12 (EC50=120±30 nM，基于 10 个供体) 的产生。Motolimod 诱导 MIP-1β 的 EC50 值为 60 nM[1]。 |
| In Vivo |
猴子皮下注射 Motolimod (1 或 10 mg/kg)，并在给药前、注射后 6、12、24 和 96 小时收集血浆。10 mg/kg Motolimod，IL-1β 的平均血浆水平从 0.5 pg/mL 的基线水平增加，在注射 6 小时后高达 9.12±2.7 ng/mL (pIL-18 的循环水平也从 ~1 pg/mL 的基线增加到 68.7±4.4 pg/mL (pIL-6 的水平，因为 IL-6 是响应 TLR8 激活而诱导的，但 IL-6 释放与 NLRP3 炎性体激活无关。此外，IFNγ 的血浆水平被评估为 NK 细胞活化对 Motolimod 处理的反应[2]。 |
| 细胞实验 |
PBMCs or purified NK cells are prepared， and the purity of NK cells is approximately 99%. NK cell-mediated cytotoxicity is assessed by Calcein AM release from labeled target cells. In brief， PBMCs or purified NK cells are cultured for 48 hours in RPMI medium in the presence of Motolimod (167 or 500 nM) before incubation with target cells[1]. |
| 动物实验 |
Monkeys[2] The male monkeys (2.9-4.9 kg) are housed individually (cage dimensions of 0.76 m wide×0.74 m deep×0.81 m in height)， but commingled periodically as part of the environmental enrichment program. The animals are also given fruit， vegetable， or additional supplements as a form of environmental enrichment， as well as given various cage enrichment devices. Animals are given Certified Primate Diet， two times daily and water ad libitum. Motolimod is administered as a bolus subcutaneous (SC) injection in the intrascapular area at doses of 1 and 10 mg/kg. Blood samples are collected at baseline (pre-dose)， and 6， 12， 24， and 96 h post injection to monitor levels of IL-1β and IL-18 in the plasma using the human MAP v.1.6 inflammation panel. |
| 激酶实验 |
Human embryonic kidney cells (HEK293) expressing TLR2， 3， 4， 5， 7， 8， or 9 are cultured in Dulbecco‘s Modified Eagle‘s Media containing 4.5 g/L L-glucose and 10% FBS. The activity of specific TLR agonists is assessed using the secretory embryonic alkaline phosphatase (SEAP) reporter gene that is linked to NF-κB activation in response to TLR stimulation. Measurement of SEAP activity using the Quanti-blue substrate after TLR agonist treatment is carried out similarly[1]. |
| 数据来源文献 |
[1]. Lu H， et al. VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC. Clin Cancer Res. 2012 Jan 15;18(2):499-509.
[2]. Dietsch GN， et al. Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist， VTX-2337， Ignites Tumoricidal Natural Killer Cell Activity. PLoS One. 2016 Feb 29;11(2):e0148764. |
| 规格 |
1mg 2mg 5mg 10mg 25mg |
| 单位 |
瓶 |
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