VLX600

Cas No.:	327031-55-0
Chemical Name:	6-Methyl-3-((2Z)-2-(1-(2-pyridinyl)ethylidene)hydrazino)-5H-[1,2,4]triazino[5,6-b]indole
Synonyms:	VLX600; VLX600; VLX600; OxPhos Inhibitor;
SMILES:	C/C(C1=NC=CC=C1)=N/NC2=NN=C3C(NC4=C3C=CC=C4C)=N2
Formula:	C17H15N7
M.Wt:	317.35
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	VLX600 is an iron-chelating inhibitor of oxidative phosphorylation (OXPHOS). VLX600 causes mitochondrial dysfunction and induces a strong shift to glycolysis. VLX600 displays selective cytotoxic activity against malignant cell and induces autophagy. Anticancer activity[1][2].
In Vivo:	VLX600 (16 mg/kg; i.v.; every third day for 16 days) shows anti-tumor activity in human tumor xenografts[2]. Animal Model: NMRI nu/nu mice (HCT116 and HT29 colon cancer xenografts)[2] Dosage: 16 mg/kg Administration: Intravenously; every third day for 16 days Result: Anti-tumor activity was observed in both HCT116 and HT29 colon cancer xenografts.
In Vitro:	VLX600 (6 μM; 72 hours) induces an autophagic response[2]. VLX600 is cytotoxic to HCT116 spheroids. VLX600 induces a HIF-1α-dependent glycolytic response. VLX600 inhibits oxygen consumption in HCT116 cells. VLX600 inhibits phosphorylation of the mTOR downstream effectors 4EBP1 and p70-S6K by an HIF-1α-independent mechanism. VLX600 preferentially leads to decreased ATP levels in cancer but not normal cells[2]. Cell Proliferation Assay[2] Cell Line: HCT116, HT29, SW620, HT8, DLD and RKO cells Concentration: 0.1, 1, 10, 100μM Incubation Time: 72 hours Result: Inhibited the proliferation of these cells. Western Blot Analysis[2] Cell Line: HCT116 cells Concentration: 6 μM Incubation Time: 72 hours Result: LC3-II was induced.
References:	[1]. Karlsson H, et al. A novel tumor spheroid model identifies selective enhancement of radiation by an inhibitor of oxidative phosphorylation. Oncotarget. 2019 Sep 3;10(51):5372-5382. [2]. Zhang X, et al. Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments. Nat Commun. 2014;5:3295.