WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202601
Description: SF1126 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.
MedKoo Cat#: 202601
Chemical Formula: C39H48N8O14
Exact Mass: 852.329
Molecular Weight: 852.84
Elemental Analysis: C, 54.92; H, 5.67; N, 13.14; O, 26.26
Synonym: SF-1126, SF1126, SF 1126
IUPAC/Chemical Name: (6Z,8S,9Z,12Z,14S,15Z,17S)-14-(carboxymethyl)-8-(3-guanidinopropyl)-6,9,12,15-tetrahydroxy-17-(hydroxymethyl)-3-oxo-1-(4-(4-oxo-8-phenyl-4H-chromen-2-yl)morpholino-4-ium)-2-oxa-7,10,13,16-tetraazaoctadeca-6,9,12,15-tetraen-18-oate
InChi Key: SVNJBEMPMKWDCO-KCHLEUMXSA-N
InChi Code: 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
SMILES Code: O=C([O-])[C@H](CO)NC([C@H](CC(O)=O)NC(CNC([C@H](CCCNC(N)=N)NC(CCC(OC[N+]1(C2=CC(C3=C(O2)C(C4=CC=CC=C4)=CC=C3)=O)CCOCC1)=O)=O)=O)=O)=O
SF1126 was designed to increase solubility and bind to specific integrins within the tumor compartment, resulting in enhanced delivery of the active compound to the tumor vasculature and tumor. SF1126 is water soluble, has favorable pharmacokinetics, and is well tolerated in murine systems. The capacity of SF1126 to inhibit U87MG and PC3 tumor growth was enhanced by the RGDS integrin (alpha v beta 3/alpha 5 beta 1) binding component, exhibiting increased activity compared with a false RADS-targeted prodrug, SF1326. Antitumor activity of SF1126 was associated with the pharmacokinetic accumulation of SF1126 in tumor tissue and the pharmacodynamic knockdown of phosphorylated AKT in vivo. Furthermore, SF1126 seems to exhibit both antitumor and antiangiogenic activity. The results support SF1126 as a viable pan PI3K inhibitor for phase I clinical trials in cancer and provide support for a new paradigm, the application of pan PI3K inhibitory prodrugs for the treatment of cancer. see http://www.ncbi.nlm.nih.gov/pubmed/18172313.
1: Peirce SK, Findley HW, Prince C, Dasgupta A, Cooper T, Durden DL. The PI-3 kinase-Akt-MDM2-survivin signaling axis in high-risk neuroblastoma: a target for PI-3 kinase inhibitor intervention. Cancer Chemother Pharmacol. 2011 Aug;68(2):325-35. Epub 2010 Oct 24. PubMed PMID: 20972874; PubMed Central PMCID: PMC3143317.
2: Ozbay T, Durden DL, Liu T, O'Regan RM, Nahta R. In vitro evaluation of pan-PI3-kinase inhibitor SF1126 in trastuzumab-sensitive and trastuzumab-resistant HER2-over-expressing breast cancer cells. Cancer Chemother Pharmacol. 2010 Mar;65(4):697-706. Epub 2009 Jul 28. PubMed PMID: 19636556; PubMed Central PMCID: PMC2808522.
3: 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. A vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, SF1126, with antitumor and antiangiogenic activity. Cancer Res. 2008 Jan 1;68(1):206-15. Erratum in: Cancer Res. 2008 Jul 15;68(1):6030. PubMed PMID: 18172313.
4: Harvey RD, Lonial S. PI3 kinase/AKT pathway as a therapeutic target in multiple myeloma. Future Oncol. 2007 Dec;3(6):639-47. Review. PubMed PMID: 18041916.