RO4929097是γ分泌酶的小分子抑制劑，IC50為4 nM，EC50為5 nM [1]。它對密切相關(guān)的蛋白酶沒(méi)有體外抑制活性。它還對75種不同類(lèi)型的其他蛋白質(zhì)具有超過(guò)100倍的選擇性[1]。RO4929097結合γ分泌酶并抑制其蛋白酶活性，因此阻斷Notch的切割并減少Notch信號。這種信號通路的上調促進(jìn)多種癌癥的腫瘤發(fā)生。

   RO4929097在體外和體內都顯示出潛在的抗腫瘤活性。它損害了黑色素瘤細胞系的生長(cháng)和人類(lèi)原發(fā)性黑色素瘤異種移植物的腫瘤形成[2]。它減緩了乳腺癌細胞系的增殖并減少了集落形成[1]。此外，RO4929097減少了結腸直腸、胰腺、肺癌和黑色素瘤異種移植模型中的腫瘤形成[1，2]。RO4929097已經(jīng)在晚期實(shí)體瘤患者的多個(gè)I/II期臨床試驗中進(jìn)行了測試，作為單一療法或與其他抗腫瘤藥物聯(lián)合使用[3-8]。

產(chǎn)品性質(zhì)：

Cas No.：847925-91-1

別名：N1-[(7S)-6,7-二氫-6-氧代-5H-二苯并[B,D]氮雜卓-7-基]-2,2-二甲基-N3-(2,2,3,3,3-五氟丙基)丙二酰胺,RG-4733

化學(xué)名： 2,2-dimethyl-N-[(7S)-6-oxo-5,7-dihydrobenzo[d][1]benzazepin-7-yl]-N'-(2,2,3,3,3-pentafluoropropyl)propanediamide

Canonical SMILES：CC(C)(C(=O)NCC(C(F)(F)F)(F)F)C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3NC1=O

分子式：C22H20F5N3O3

分子量：469.4

溶解度：≥ 23.47 mg/mL in DMSO, ≥ 45.2 mg/mL in EtOH with ultrasonic

儲存條件：Store at -20°C

注意事項：

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References:

1. Luistro L, He W, Smith M et al. Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. Cancer Res 2009; 69: 7672-7680.

2. Huynh C, Poliseno L, Segura MF et al. The novel gamma secretase inhibitor RO4929097 reduces the tumor initiating potential of melanoma. PLoS One 2011; 6: e25264.

3. Richter S, Bedard PL, Chen EX et al. A phase I study of the oral gamma secretase inhibitor R04929097 in combination with gemcitabine in patients with advanced solid tumors (PHL-078/CTEP 8575). Invest New Drugs 2014; 32: 243-249.

4. Sahebjam S, Bedard PL, Castonguay V et al. A phase I study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (PJC-004/NCI 8503). Br J Cancer 2013; 109: 943-949.

5. Diaz-Padilla I, Hirte H, Oza AM et al. A phase Ib combination study of RO4929097, a gamma-secretase inhibitor, and temsirolimus in patients with advanced solid tumors. Invest New Drugs 2013; 31: 1182-1191.

6. Tolcher AW, Messersmith WA, Mikulski SM et al. Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors. J Clin Oncol 2012; 30: 2348-2353.

7. Strosberg JR, Yeatman T, Weber J et al. A phase II study of RO4929097 in metastatic colorectal cancer. Eur J Cancer 2012; 48: 997-1003.

8. Kolb EA, Gorlick R, Keir ST et al. Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a gamma-secretase inhibitor targeting notch signaling. Pediatr Blood Cancer 2012; 58: 815-818.