WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206109
Description: VS-5584, also known as SB2343, is a potent and selective inhibitor of both phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) kinase in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. PI3K/mTOR kinase inhibitor VS-5584 inhibits mTOR kinase and all class I PI3K isoforms. Consequently, this disrupts phosphorylation of substrates downstream of PI3K and mTOR and may result in apoptosis and growth inhibition in susceptible tumor cells. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy.
MedKoo Cat#: 206109
Chemical Formula: C17H22N8O
Exact Mass: 354.19166
Molecular Weight: 354.41
Elemental Analysis: C, 57.61; H, 6.26; N, 31.62; O, 4.51
Synonym: VS5584; VS 5584; VS5584; SB2343; SB2343; SB 2343.
IUPAC/Chemical Name: 5-(9-isopropyl-8-methyl-2-morpholino-9H-purin-6-yl)pyrimidin-2-amine
InChi Key: QYBGBLQCOOISAR-UHFFFAOYSA-N
InChi Code: InChI=1S/C17H22N8O/c1-10(2)25-11(3)21-14-13(12-8-19-16(18)20-9-12)22-17(23-15(14)25)24-4-6-26-7-5-24/h8-10H,4-7H2,1-3H3,(H2,18,19,20)
SMILES Code: NC1=NC=C(C2=C3N=C(C)N(C(C)C)C3=NC(N4CCOCC4)=N2)C=N1
VS-5584 is a selective dual pan-PI3K/mTOR inhibitor being developed by Verastem. Research has shown that VS-5584 has equivalent potency against mTOR (IC(50) = 37 nmol/L) and all class I phosphoinositide 3-kinase (PI3K) isoforms IC(50): PI3Kα = 16 nmol/L; PI3Kβ = 68 nmol/L; PI3Kγ = 25 nmol/L; PI3Kδ = 42 nmol/L, without relevant activity on 400 lipid and protein kinases. VS-5584 shows robust modulation of cellular PI3K/mTOR pathways, inhibiting phosphorylation of substrates downstream of PI3K and mTORC1/2. VS-5584 exhibits favorable pharmacokinetic properties after oral dosing in mice and is well tolerated. VS-5584 induces long-lasting and dose-dependent inhibition of PI3K/mTOR signaling in tumor tissue, leading to tumor growth inhibition in various rapalog-sensitive and -resistant human xenograft models. Furthermore, VS-5584 is synergistic with an EGF receptor inhibitor in a gastric tumor model. The unique selectivity profile and favorable pharmacologic and pharmaceutical properties of VS-5584 and its efficacy in a wide range of human tumor models supports further investigations of VS-5584 in clinical trials.
1: Shao Z, Bao Q, Jiang F, Qian H, Fang Q, Hu X. VS-5584, a Novel PI3K-mTOR Dual Inhibitor, Inhibits Melanoma Cell Growth In Vitro and In Vivo. PLoS One. 2015 Jul 23;10(7):e0132655. doi: 10.1371/journal.pone.0132655. eCollection 2015. PubMed PMID: 26204252; PubMed Central PMCID: PMC4512677.
2: Kolev VN, Wright QG, Vidal CM, Ring JE, Shapiro IM, Ricono J, Weaver DT, Padval MV, Pachter JA, Xu Q. PI3K/mTOR dual inhibitor VS-5584 preferentially targets cancer stem cells. Cancer Res. 2015 Jan 15;75(2):446-55. doi: 10.1158/0008-5472.CAN-14-1223. Epub 2014 Nov 28. PubMed PMID: 25432176.
3: Poulsen A, Nagaraj H, Lee A, Blanchard S, Soh CK, Chen D, Wang H, Hart S, Goh KC, Dymock B, Williams M. Structure and ligand-based design of mTOR and PI3-kinase inhibitors leading to the clinical candidates VS-5584 (SB2343) and SB2602. J Chem Inf Model. 2014 Nov 24;54(11):3238-50. doi: 10.1021/ci500493m. Epub 2014 Oct 23. PubMed PMID: 25317974.
4: Hart S, Novotny-Diermayr V, Goh KC, Williams M, Tan YC, Ong LC, Cheong A, Ng BK, Amalini C, Madan B, Nagaraj H, Jayaraman R, Pasha KM, Ethirajulu K, Chng WJ, Mustafa N, Goh BC, Benes C, McDermott U, Garnett M, Dymock B, Wood JM. VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer. Mol Cancer Ther. 2013 Feb;12(2):151-61. doi: 10.1158/1535-7163.MCT-12-0466. Epub 2012 Dec 27. PubMed PMID: 23270925; PubMed Central PMCID: PMC3588144.