LW 6

LW6, was first identified and reported by a group scientists from Korea. LW8 was found to inhibits the accumulation of HIF-1alpha. LW6 decreased HIF-1alpha protein expression without affecting HIF-1beta expression. It was further found that LW8 promoted the degradation of wild type HIF-1alpha, but not of a DM-HIF-1alpha with modifications of P402A and P564A, at hydroxylation sites in the oxygen-dependent degradation domain (ODDD). LW6 did not affect the activity of prolyl hydroxylase (PHD), but induced the expression of von Hippel-Lindau (VHL), which interacts with prolyl-hydroxylated HIF-1alpha for proteasomal degradation. In the presence of LW8, knockdown of VHL did not abolish HIF-1alpha protein accumulation, indicating that LW8 degraded HIF-1alpha via regulation of VHL expression. In mice carrying xenografts of human colon cancer HCT116 cells, LW8 demonstrated strong anti-tumor efficacy in vivo and caused a decrease in HIF-1alpha expression in frozen-tissue immunohistochemical staining. These data suggest that LW8 may be valuable in the development of a HIF-1alpha inhibitor for cancer treatment. (source: Biochem Pharmacol. 2010 Oct 1;80(7):982-9.)

Product information

CAS Number: 934593-90-5

Molecular Weight: 435.51

Formula: C26H29NO5

Synonym:

CAY-10585

CAY10585

CAY 10585

LW6

LW-6

LW 6

Chemical Name: methyl 3-(2-(4-(adamantan-1-yl)phenoxy)acetamido)-4-hydroxybenzoate

Smiles: COC(=O)C1=CC(NC(=O)COC2C=CC(=CC=2)C23CC4CC(C2)CC(C3)C4)=C(O)C=C1

InChiKey: BJRPPNOJYFZSLY-UHFFFAOYSA-N

InChi: InChI=1S/C26H29NO5/c1-31-25(30)19-2-7-23(28)22(11-19)27-24(29)15-32-21-5-3-20(4-6-21)26-12-16-8-17(13-26)10-18(9-16)14-26/h2-7,11,16-18,28H,8-10,12-15H2,1H3,(H,27,29)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

LW6 affects the stability of the HIF-1α protein. LW6 promotes the degradation of wild type HIF-1α, but not of a DM-HIF-1α with modifications of P402A and P564A, at hydroxylation sites in the oxygen-dependent degradation domain. LW6 induces the expression of von Hippel-Lindau (VHL), which interacts with prolyl-hydroxylated HIF-1α for proteasomal degradation. In the presence of LW6, knockdown of VHL does not abolish HIF-1α protein accumulation, indicating that LW6 degraded HIF-1α via regulation of VHL expression. In MDCKII-BCRP cells overexpressing BCRP, LW6 enhances significantly the cellular accumulation of mitoxantrone, a BCRP substrate. LW6 also down-regulates BCRP expression at concentrations of 0.1-10 µM. LW6 inhibits the expression of HIF 1α induced by hypoxia in A549 cells at 20 µM, independently of the von Hippel Lindau protein. LW6 induces hypoxia selective apoptosis together with a reduction in the mitochondrial membrane potential.

References:

1. Liu XY, Wang BJ, Jiang CY, Liu SJ. Ornithinimicrobium pekingense sp. nov., isolated from activated sludge. Int J Syst Evol Microbiol. 2008 Jan;58(Pt 1):116-9. PubMed PMID: 18175694.
2. Whitehead L. Toward a trajectory of identity reconstruction in chronic fatigue syndrome/myalgic encephalomyelitis: a longitudinal qualitative study. Int J Nurs Stud. 2006 Nov;43(8):1023-31. Epub 2006 Mar 9. PubMed PMID: 16527282.

Products are for research use only. Not for human use.