PIK-75 hydrochloride 是一種可逆的DNA-PK和p110α-選擇性抑制劑，抑制 DNA-PK，p110α和 p110γ，可誘導凋亡。PIK-75是PI3K p110α亞型的特異性抑制劑，IC50為5.8 nM [1]。 在急性髓細胞白血病細胞中，PIK-75靶向PI3K的p110α亞型，這導致Bcl-xL和Bak之間連接的丟失。PIK-75也短暫降低Cdk7/9，導致Mcl-1蛋白的丟失，并減輕其對促凋亡Bak的抑制。Bcl-xL和Mcl-1的同時缺失導致細胞快速凋亡。[2]在人單核細胞-內皮細胞中，PIK-75抑制下游信號事件，包括AKT磷酸化、IKK活化和NF-kB轉錄。PIK-75抑制體外和體內TNF-α和IL-6的產生，降低E-選擇素、ICAM-1和VCAM-1的表達，并阻斷細胞粘附[3]。在人類平滑肌細胞中，PIK-75降低了哮喘和非哮喘細胞中TNF-α誘導的CD38表達[4]。在胰腺β細胞中，使用PIK-75的急性治療增強了葡萄糖誘導的胰島素分泌[5]。

   在體內，PIK-75顯著抑制與葡聚糖硫酸鈉誘導的小鼠結腸炎相關的組織學異常。PIK-75可以減輕結腸的實驗性炎癥[3]。

產品性質：

Cas No.:372196-77-5

別名:2-甲基-5-硝基苯磺酸[(6-溴咪唑并[1,2-A]吡啶-3-基)亞甲基]甲基肼鹽酸鹽

化學名: N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide;hydrochloride

Canonical SMILES:CC1=C(C=C(C=C1)[N+](=O)[O-])S(=O)(=O)N(C)N=CC2=CN=C3N2C=C(C=C3)Br.Cl

分子式:C16H14BrN5O4S.HCl

分子量:488.74

溶解度；≥ 8.15mg/mL in DMSO with gentle warming

儲存條件：Store at -20°C

注意事項：

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References:

[1]. Zheng Z, Amran SI, Thompson PE, Jennings IG. Isoform-selective inhibition of phosphoinositide 3-kinase: identification of a new region of nonconserved amino acids critical for p110α inhibition. Mol Pharmacol. 2011 Oct;80(4):657-64.

[2]. Thomas D, Powell JA, Vergez F, Segal DH, Nguyen NY, Baker A, Teh TC, Barry EF, Sarry JE, Lee EM, Nero TL, Jabbour AM, Pomilio G, Green BD, Manenti S, Glaser SP, Parker MW, Lopez AF, Ekert PG, Lock RB, Huang DC, Nilsson SK, Récher C, Wei AH, Guthridge MA. Targeting acute myeloid leukemia by dual inhibition of PI3K signaling and Cdk9-mediated Mcl-1 transcription. Blood. 2013 Aug 1;122(5):738-48.

[3]. Dagia NM, Agarwal G, Kamath DV, Chetrapal-Kunwar A, Gupte RD, Jadhav MG, Dadarkar SS, Trivedi J, Kulkarni-Almeida AA, Kharas F, Fonseca LC, Kumar S, Bhonde MR. A preferential p110alpha/gamma PI3K inhibitor attenuates experimental inflammation by suppressing the production of proinflammatory mediators in a NF-kappaB-dependent manner. Am J Physiol Cell Physiol. 2010 Apr;298(4):C929-41.

[4]. Jude JA, Tirumurugaan KG, Kang BN, Panettieri RA, Walseth TF, Kannan MS. Regulation of CD38 expression in human airway smooth muscle cells: role of class I phosphatidylinositol 3 kinases. Am J Respir Cell Mol Biol. 2012 Oct;47(4):427-35.

[5]. Aoyagi K, Ohara-Imaizumi M, Nishiwaki C, Nakamichi Y, Ueki K, Kadowaki T, Nagamatsu S. Acute inhibition of PI3K-PDK1-Akt pathway potentiates insulin secretion through upregulation of newcomer granule fusions in pancreatic β-cells. PLoS One. 2012;7(10):e47381.