Ki16425

製品コードS1315 バッチS131504

印刷

化学情報

Chemical Structure Synonyms Debio 0719 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C23H23ClN2O5S
分子量 474.96 CAS No. 355025-24-0
Solubility (25°C)* 体外 DMSO 94 mg/mL (197.91 mM)
Ethanol 94 mg/mL (197.91 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Ki16425 is a competitive, potent and reversible antagonist to LPA1, LPA2 and LPA3 with Ki of 0.34 μM, 6.5 μM and 0.93 μM in RH7777 cell lines, respectively, shows no activity at LPA4, LPA5, LPA6.
in vitro Kil6425 preferentially inhibits LPA1- and LPA3-mediated responses but has only a moderate effect on LPA2. This compound inhibits the LPA-induced Ca(2+) response in THP-1 cells, 3T3 fibroblasts, and A431 cells, but had only a marginal effect in PC-12 cells and HL-60 cells, which means that it seems to be a useful tool for evaluating the involvement of specific LPA receptors in the short-term response to LPA. It inhibits long-term DNA synthesis and cell migration as induced by LPA in Swiss 3T3 fibroblasts. [1] This chemical reduces the LPA-induced activation of p42/p44 mitogen activated protein kinase (MAPK), while acting as a weak stimulator of p42/p44 MAPK on its own, properties typical of a protean agonist. It also significantly reduces the NGF-induced stimulation of p42/p44 MAPK and inhibited NGF-stimulated neurite outgrowth in PC-12 cells. [2] It markedly inhibits the expressions of COX-2 protein induced by synovial fluids. The enhancement of the IL-1 action by LPA on COX-2 expression is also inhibited by this compound. [3]
in vivo Ki-16425 (30 mg/kg, i.p.) completely blocks LPA-induced neuropathic pain-like behaviors, when administered 30 min but not 90 min before lysophosphatidic acid injection, suggesting that this compound is a short-lived inhibitor. This chemical also inhibits nerve injury-induced up-regulation of Caα2δ-1 in the dorsal root ganglion and reduction of SP immunoreactivity in the spinal dorsal horn. [4]

プロトコル(参考用のみ)

キナーゼアッセイ Inositol Phosphate Production.
RH7777 cells are incubated for 1 min with or without Ki16425, and the inositol phosphates (sum of inositol bisphosphate and inositol trisphosphate) are measured. The results are normalized to 105 dpm of the total radioactivity incorporated into the cellular inositol lipids, and the radioactivity of trichloroacetic acid (5%)-insoluble fraction is considered as the total radioactivity. The Ki values for this compound is estimated from inositol phosphate responses or Ca2+ responses, based on the following equation: Ki = (EC50 × B)/(EC50′ - EC50), where B is the concentration of this chemical, and EC50 and EC50′ are the half-maximal effective concentration of LPA in the absence and presence of this compound. The half-maximal effective concentration is estimated as a value that graphically gives a 50% maximal response. With regard to the Schild regressions, the half-maximal effective concentration is estimated from the Scatchard plots. The Ki value is determined by plotting the log of Dose Ratio-1 at each concentration of this chemical against the log concentration of this compound. The x-intercept of the linear transformation equals the inverse log of the Ki.
動物実験 動物モデル Male standard ddY-strain mice are used.
投薬量 30 mg/kg.
投与方法 Administered via i.p.

参考

  • https://pubmed.ncbi.nlm.nih.gov/14500756/
  • https://pubmed.ncbi.nlm.nih.gov/16945108/
  • https://pubmed.ncbi.nlm.nih.gov/18802115/
  • https://pubmed.ncbi.nlm.nih.gov/19222705/

カスタマーフィードバック

Data from [J Cell Mol Med, 2014, 18(1), 156-69]

Data from [Data independently produced by Front Physiol, 2014, 5, 413]

Data from [Data independently produced by , , Neuropharmacology, 2016, 103:92-103]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Cancer-associated fibroblasts maintain critical pancreatic cancer cell lipid homeostasis in the tumor microenvironment [ Cell Rep, 2024, 43(11):114972] PubMed: 39535921
YAP/TAZ mediates resistance to KRAS inhibitors through inhibiting proapoptosis and activating the SLC7A5/mTOR axis [ JCI Insight, 2024, 9(24)e178535] PubMed: 39704172
Deficiency of lysophosphatidic acid receptor 3 decreases erythropoietin production in hypoxic mouse kidneys [ Lipids Health Dis, 2024, 23(1):381] PubMed: 39558335
Lysophosphatidic acid is associated with oocyte maturation by enhancing autophagy via PI3K-AKT-mTOR signaling pathway in granulosa cells [ J Ovarian Res, 2023, 16(1):137] PubMed: 37434211
Lysophosphatidic acid is associated with oocyte maturation by enhancing autophagy via PI3K-AKT-mTOR signaling pathway in granulosa cells [ J Ovarian Res, 2023, 16(1):137] PubMed: 37434211
Recapitulating early human development with 8C-like cells [ Cell Rep, 2022, 39(12):110994] PubMed: 35732112
Lysophosphatidic acid suppresses apoptosis of high-grade serous ovarian cancer cells by inducing autophagy activity and promotes cell-cycle progression via EGFR-PI3K/Aurora-AThr288-geminin dual signaling pathways [ Front Pharmacol, 2022, 13:1046269] PubMed: 36601056
LPA signaling acts as a cell-extrinsic mechanism to initiate cilia disassembly and promote neurogenesis [ Nat Commun, 2021, 12(1):662] PubMed: 33510165
Lysophosphatidic Acid-Induced EGFR Transactivation Promotes Gastric Cancer Cell DNA Replication by Stabilizing Geminin in the S Phase [ Front Pharmacol, 2021, 12:706240] PubMed: 34658851
LPA receptor1 antagonists as anticancer agents suppress human lung tumours. [ Eur J Pharmacol, 2020, 868:172886] PubMed: 31866407

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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