VH 298|VH298;VH298|CAS 2097381-85-4

Cas No.:	2097381-85-4
Chemical Name:	(2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide
Synonyms:	VH298;VH298
SMILES:	C(C1(C(NC(C(C)(C)C)C(N2CC(O)CC2C(NCC2C=CC(C3SC=NC=3C)=CC=2)=O)=O)=O)CC1)#N
Formula:	C₂₇H₃₃N₅O₄S
M.Wt:	523.652
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Publication:	[1]. Frost J, et al. Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition. Nat Commun. 2016 Nov 4;7:13312.

Description:	VH-298 is a highly potent inhibitor of the VHL:HIF-α interaction with a Kd value of 80 to 90 nM, used in PROTAC technology.
Target:	Kd: 80 to 90 nM (VHL:HIF-α)[1]
In Vitro:	VH-298 is a potent, cell permeable and non-toxic chemical probe that triggers the hypoxic response by blocking the VHL. VH-298 is a highly potent inhibitor of the VHL:HIF-α interaction with Kd values of 90 and 80 nM in isothermal titration calorimetry and competitive fluorescence polarization assay. VH-298 binds with VHL complex very fast and dissociates slowly. VH-298 at 50 μM concentration exhibits negligible off-target effects in vitro against more than 100 tested cellular kinases, GPCRs and ion channels. VH-298 is cell permeable and not toxic to cells. The measured permeability of VH-298 is found to be 19.4 nm s -1. VH-298 induces concentration- and time-dependent on-target specific accumulation of hydroxylated HIF-α in human cell lines, including HeLa cancer cells and renal cell carcinoma 4 (RCC4) cells. VH-298 increases mRNA levels of EPO by 2.5-fold in RCC4-HA-VHL, but not in VHL-null RCC4-HA, indicating that pharmacological inhibition of VHL is able to stimulate endogenous EPO synthesis. VH-298 proves as effective as hypoxia in raising PHD2 and HK2 protein levels, however in HFF the BNIP3 protein level increases more with VH-298 treatment than hypoxia treatment[1].
Kinase Assay:	VH-298 is screened at 50 μM concentration against a panel of 50 kinases. The remaining kinase activity is recorded in the end of the assay. The data is reported as average % activity remaining of assay duplicates for each kinase tested[1].
Cell Assay:	Death of CTLs is analyzed by staining with 4′,6-diamidino-2-phenylindole (DAPI). Cells are plated in 96-well plates at 1×106 and treated with VHL inhibitors (VH-298) and respective non-binding cis-analogues for 24 h. Cells are spun down and resuspended in HBSS containing DAPI to identify dead and dying populations[1].
References:	[1]. Frost J, et al. Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition. Nat Commun. 2016 Nov 4;7:13312.

Cat. No.	Product name	Field of application
DC32733	VH032-linker 5	VH032-linker 5 is a derivative of the proteolysis-targeting chimera technology (PROTAC) for PROTAC research and development; by incorporating an E3 ligase ligand and an alkyl C4 linker with terminal carboxylic acid, it is ready for conjugation to a target protein ligand.
DC26169	MS1943	MS1943 is a first-in-class, orally bioavailable EZH2 selective degrader, with an IC50 of 120 nM. MS1943 significantly reduces EZH2 protein levels in numerous triple-negative breast cancer (TNBC) and other cancer and noncancerous cell lines.
DC26119	VHL ligand 2 hydrochloride	VHL ligand 2 hydrochloride) is the (S,R,S)-AHPC-based VHL ligand used in the recruitment of the von Hippel-Lindau (VHL) protein. (S,R,S)-AHPC-Me hydrochloride can be used to synthesize ARV-771, a von Hippel-Landau (VHL) E3 ligase-based BET PROTAC degrader.
DC21962	TL13-12	TL13-12 is a novel Anaplastic Lymphoma Kinase (ALK)-PROTAC developed through conjugation of TAE684 and the cereblon ligand pomalidomide.
DC26122	Pomalidomide-C2-NH2 hydrochloride	Pomalidomide-C2-NH2 hydrochloride is a synthesized E3 ligase ligand-linker conjugate that incorporates the Pomalidomide based cereblon ligand and a linker used in PROTAC technology.
DC21360	MZ1	MZ1 is a PROTAC that tethers JQ1 to a ligand for the E3 ubiquitin ligase VHL, triggers, induces degradation of the BET bromodomain BRD4.
DC21351	MS4078	MS4078 is a novel PROTAC (degrader) of ALK, potently decreases cellular levels of oncogenic active ALK fusion proteins in a concentration- and time-dependent manner in SU-DHL-1 lymphoma and NCI-H2228 lung cancer cells (DC50=11 nM).
DC12191	JQ-35-(S)	JQ-35, (S)- is an inhibitor of the Bromodomain and Extra-Terminal (BET) family bromodomain-containing proteins with potential antineoplastic activity.
DC20367	dTRIM24	dTRIM24 is a potent TRIM24 bromodomain inhibitor with IC50 of 217.8 nM (TRIM24 ligand displacement).
DC21893	dBET57	dBET57 is a novel BRD4 heterobifunctional small-molecule ligand (PROTAC), exhibits significant and selective degradation of BRD4 BD1 (DC50/5h=500 nM), but is inactive on BRD4 BD2..