For research use only. Not for therapeutic Use.
SF1126 (Cat No.:I009452) is a water soluble, small-molecule prodrug containing the pan-PI3K/mTOR inhibitor LY294002/SF1101 conjugated to the RGD-containing tetra-peptide SF1174 with potential antineoplastic and antiangiogenic activities. The targeting peptide SF1174 moiety of pan-PI3K/mTOR inhibitor SF1126 selectively binds to cell surface integrins and, upon cell entry, the agent is hydrolyzed to the active drug SF1101; SF1101 selectively inhibits all isoforms of phosphoinositide-3-kinase (PI3K) and other members of the PI3K superfamily, such as the mammalian target of rapamycin (mTOR) and DNA-PK.
| Catalog Number | I009452 |
| CAS Number | 936487-67-1 |
| Synonyms | SF-1126 SF1126; SF 1126;(8S,14S,17S)-14-(carboxymethyl)-8-(3-guanidinopropyl)-17-(hydroxymethyl)-3,6,9,12,15-pentaoxo-1-(4-(4-oxo-8-phenyl-4H-chromen-2-yl)morpholino-4-ium)-2-oxa-7,10,13,16-tetraazaoctadecan-18-oate |
| Molecular Formula | C39H48N8O14 |
| Purity | ≥95% |
| Solubility | Soluble in DMSO, not in water |
| Storage | 0 - 4 °C for short term, or -20 °C for long term |
| IUPAC Name | (2S)-2-[[(2S)-3-carboxy-2-[[2-[[(2S)-5-(diaminomethylideneamino)-2-[[4-oxo-4-[[4-(4-oxo-8-phenylchromen-2-yl)morpholin-4-ium-4-yl]methoxy]butanoyl]amino]pentanoyl]amino]acetyl]amino]propanoyl]amino]-3-hydroxypropanoate |
| InChI | InChI=1S/C39H48N8O14/c40-39(41)42-13-5-10-26(36(55)43-20-31(51)45-27(18-33(52)53)37(56)46-28(21-48)38(57)58)44-30(50)11-12-34(54)60-22-47(14-16-59-17-15-47)32-19-29(49)25-9-4-8-24(35(25)61-32)23-6-2-1-3-7-23/h1-4,6-9,19,26-28,48H,5,10-18,20-22H2,(H9-,40,41,42,43,44,45,46,50,51,52,53,55,56,57,58)/t26-,27-,28-/m0/s1 |
| InChIKey | SVNJBEMPMKWDCO-KCHLEUMXSA-N |
| SMILES | C1COCC[N+]1(COC(=O)CCC(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)[O-])C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=CC=C4 |
| Reference | </br>1:Association of high microvessel αvβ3 and low PTEN with poor outcome in stage 3 neuroblastoma: rationale for using first in class dual PI3K/BRD4 inhibitor, SF1126. Erdreich-Epstein A, Singh AR, Joshi S, Vega FM, Guo P, Xu J, Groshen S, Ye W, Millard M, Campan M, Morales G, Garlich JR, Laird PW, Seeger RC, Shimada H, Durden DL.Oncotarget. 2016 Nov 16. doi: 10.18632/oncotarget.13386. [Epub ahead of print] PMID: 27907905 Free Article</br>2:Single Agent and Synergistic Activity of the /First-in-Class/ Dual PI3K/BRD4 Inhibitor SF1126 with Sorafenib in Hepatocellular Carcinoma. Singh AR, Joshi S, Burgoyne AM, Sicklick JK, Ikeda S, Kono Y, Garlich JR, Morales GA, Durden DL.Mol Cancer Ther. 2016 Nov;15(11):2553-2562. Epub 2016 Aug 5. PMID: 27496136 Free PMC Article</br>3:Combination of SF1126 and gefitinib induces apoptosis of triple-negative breast cancer cells through the PI3K/AKT-mTOR pathway. Deng M, Wang J, Chen Y, Zhang L, Liu D.Anticancer Drugs. 2015 Apr;26(4):422-7. doi: 10.1097/CAD.0000000000000202. PMID: 25588160 </br>4:Pan-PI-3 kinase inhibitor SF1126 shows antitumor and antiangiogenic activity in renal cell carcinoma. Joshi S, Singh AR, Durden DL.Cancer Chemother Pharmacol. 2015 Mar;75(3):595-608. doi: 10.1007/s00280-014-2639-x. Epub 2015 Jan 13. PMID: 25578041 </br>5:Anti-tumor effect of a novel PI3-kinase inhibitor, SF1126, in (12) V-Ha-Ras transgenic mouse glioma model. Singh AR, Joshi S, George E, Durden DL.Cancer Cell Int. 2014 Nov 12;14(1):105. doi: 10.1186/s12935-014-0105-9. eCollection 2014. PMID: 25425962 Free PMC Article</br>6:An integrin-targeted, pan-isoform, phosphoinositide-3 kinase inhibitor, SF1126, has activity against multiple myeloma in vivo. De P, Dey N, Terakedis B, Bergsagel PL, Li ZH, Mahadevan D, Garlich JR, Trudel S, Makale MT, Durden DL.Cancer Chemother Pharmacol. 2013 Apr;71(4):867-81. doi: 10.1007/s00280-013-2078-0. Epub 2013 Jan 25. PMID: 23355037 Free PMC Article</br>7:Phase I pharmacokinetic and pharmacodynamic study of the pan-PI3K/mTORC vascular targeted pro-drug SF1126 in patients with advanced solid tumours and B-cell malignancies. Mahadevan D, Chiorean EG, Harris WB, Von Hoff DD, Stejskal-Barnett A, Qi W, Anthony SP, Younger AE, Rensvold DM, Cordova F, Shelton CF, Becker MD, Garlich JR, Durden DL, Ramanathan RK.Eur J Cancer. 2012 Dec;48(18):3319-27. doi: 10.1016/j.ejca.2012.06.027. Epub 2012 Aug 23. PMID: 22921184 Free PMC Article</br>8:In vitro evaluation of pan-PI3-kinase inhibitor SF1126 in trastuzumab-sensitive and trastuzumab-resistant HER2-over-expressing breast cancer cells. Ozbay T, Durden DL, Liu T, O/’Regan RM, Nahta R.Cancer Chemother Pharmacol. 2010 Mar;65(4):697-706. doi: 10.1007/s00280-009-1075-9. Epub 2009 Jul 28. PMID: 19636556 Free PMC Article</br>9:A vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, SF1126, with antitumor and antiangiogenic activity. Garlich JR, De P, Dey N, Su JD, Peng X, Miller A, Murali R, Lu Y, Mills GB, Kundra V, Shu HK, Peng Q, Durden DL.Cancer Res. 2008 Jan 1;68(1):206-15. doi: 10.1158/0008-5472.CAN-07-0669. Erratum in: Cancer Res. 2008 Jul 15;68(1):6030. PMID: 18172313 Free Article |
