PIK-75 hydrochloride 是一种可逆的DNA-PK和p110α-选择性抑制剂，抑制 DNA-PK，p110α和 p110γ，可诱导凋亡。PIK-75是PI3K p110α亚型的特异性抑制剂，IC50为5.8 nM [1]。 在急性髓细胞白血病细胞中，PIK-75靶向PI3K的p110α亚型，这导致Bcl-xL和Bak之间连接的丢失。PIK-75也短暂降低Cdk7/9，导致Mcl-1蛋白的丢失，并减轻其对促凋亡Bak的抑制。Bcl-xL和Mcl-1的同时缺失导致细胞快速凋亡。[2]在人单核细胞-内皮细胞中，PIK-75抑制下游信号事件，包括AKT磷酸化、IKK活化和NF-kB转录。PIK-75抑制体外和体内TNF-α和IL-6的产生，降低E-选择素、ICAM-1和VCAM-1的表达，并阻断细胞粘附[3]。在人类平滑肌细胞中，PIK-75降低了哮喘和非哮喘细胞中TNF-α诱导的CD38表达[4]。在胰腺β细胞中，使用PIK-75的急性治疗增强了葡萄糖诱导的胰岛素分泌[5]。

   在体内，PIK-75显著抑制与葡聚糖硫酸钠诱导的小鼠结肠炎相关的组织学异常。PIK-75可以减轻结肠的实验性炎症[3]。

产品性质：

Cas No.:372196-77-5

别名:2-甲基-5-硝基苯磺酸[(6-溴咪唑并[1,2-A]吡啶-3-基)亚甲基]甲基肼盐酸盐

化学名: 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

储存条件：Store at -20°C

注意事项：

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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.