VH-298 | CAS#2097381-85-4 | VHL inhibitor

MedKoo Cat#: 530908 | Name: VH298

Description:

WARNING: This product is for research use only, not for human or veterinary use.

VH-298 is a potent VHL inhibitor that stabilizes HIF-α and elicits a hypoxic response via a different mechanism, that is the blockade of the VHL:HIF-α protein-protein interaction downstream of HIF-α hydroxylation by PHD enzymes. VH298 represents a high-quality chemical probe of the HIF signalling cascade and an attractive starting point to the development of potential new therapeutics targeting hypoxia signalling.

Chemical Structure

VH298

CAS#2097381-85-4

Theoretical Analysis

MedKoo Cat#: 530908

Name: VH298

CAS#: 2097381-85-4

Chemical Formula: C27H33N5O4S

Exact Mass: 523.2253

Molecular Weight: 523.65

Elemental Analysis: C, 61.93; H, 6.35; N, 13.37; O, 12.22; S, 6.12

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to Ship
25mg	USD 250.00	Ready to Ship
50mg	USD 450.00	Ready to Ship
100mg	USD 750.00	Ready to Ship
200mg	USD 1,250.00	Ready to Ship
500mg	USD 2,850.00	Ready to Ship

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Synonym

VH-298; VH 298; VH298.

IUPAC/Chemical Name

(2S,4R)-1-((S)-2-(1-cyanocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

InChi Key

NDVQUNZCNAMROD-RZUBCFFCSA-N

InChi Code

InChI=1S/C27H33N5O4S/c1-16-21(37-15-30-16)18-7-5-17(6-8-18)12-29-23(34)20-11-19(33)13-32(20)24(35)22(26(2,3)4)31-25(36)27(14-28)9-10-27/h5-8,15,19-20,22,33H,9-13H2,1-4H3,(H,29,34)(H,31,36)/t19-,20+,22-/m1/s1

SMILES Code

O=C([C@H]1N(C([C@@H](NC(C2(CC2)C#N)=O)C(C)(C)C)=O)C[C@H](O)C1)NCC3=CC=C(C4=C(C)N=CS4)C=C3

Appearance

Solid powder

Purity

>97% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#T22D09P30

QC Data

View QC data: current batch, Lot#T22D09P30

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

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.

In vitro activity:

VH298 increased the HIF-1α protein level in both the KO and WT groups and synchronously up-regulated IL-17 and GLUT1 expression in Th17 cells (Figure 6A). As expected, accumulation of HIF-1α partially restored Th17 cell differentiation in KO mice (Figure 6B). Moreover, expression of Rorγt also significantly increased upon VH298 stimulation (Figure 6C). Reference: Front Immunol. 2020 Aug 18;11:2040. https://pubmed.ncbi.nlm.nih.gov/32973810/

In vivo activity:

VH298-treated wounds in rats healed much faster than the PBS-treated wounds at postoperative days 7, 14, and 21, and no significant effect in the very early stage (3 days) was observed (Figure 3(a)). Reference: J Diabetes Res. 2019 Feb 17;2019:1897174. https://pubmed.ncbi.nlm.nih.gov/30911550/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	57.29
	DMSO	66.4	126.84
	Ethanol	60.8	116.09
	Ethanol:PBS (pH 7.2) (1:9)	0.1	0.19

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 523.65 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Zhang Q, Wang L, Jiang J, Lin S, Luo A, Zhao P, Tan W, Zhang M. Critical Role of AdipoR1 in Regulating Th17 Cell Differentiation Through Modulation of HIF-1α-Dependent Glycolysis. Front Immunol. 2020 Aug 18;11:2040. doi: 10.3389/fimmu.2020.02040. PMID: 32973810; PMCID: PMC7461876. 2. Soares P, Gadd MS, Frost J, Galdeano C, Ellis L, Epemolu O, Rocha S, Read KD, Ciulli A. Group-Based Optimization of Potent and Cell-Active Inhibitors of the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase: Structure-Activity Relationships Leading to the Chemical Probe (2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (VH298). J Med Chem. 2018 Jan 25;61(2):599-618. doi: 10.1021/acs.jmedchem.7b00675. Epub 2017 Sep 18. PMID: 28853884; PMCID: PMC5788404. 3. Qiu S, Jia Y, Sun Y, Han P, Xu J, Wen G, Chai Y. Von Hippel-Lindau (VHL) Protein Antagonist VH298 Improves Wound Healing in Streptozotocin-Induced Hyperglycaemic Rats by Activating Hypoxia-Inducible Factor- (HIF-) 1 Signalling. J Diabetes Res. 2019 Feb 17;2019:1897174. doi: 10.1155/2019/1897174. PMID: 30911550; PMCID: PMC6398031.

In vitro protocol:

In vivo protocol:

1. Qiu S, Jia Y, Sun Y, Han P, Xu J, Wen G, Chai Y. Von Hippel-Lindau (VHL) Protein Antagonist VH298 Improves Wound Healing in Streptozotocin-Induced Hyperglycaemic Rats by Activating Hypoxia-Inducible Factor- (HIF-) 1 Signalling. J Diabetes Res. 2019 Feb 17;2019:1897174. doi: 10.1155/2019/1897174. PMID: 30911550; PMCID: PMC6398031.

1: Wang Y, Cao Z, Wei Q, Ma K, Hu W, Huang Q, Su J, Li H, Zhang C, Fu X. VH298-loaded extracellular vesicles released from gelatin methacryloyl hydrogel facilitate diabetic wound healing by HIF-1α-mediated enhancement of angiogenesis. Acta Biomater. 2022 Jul 15;147:342-355. doi: 10.1016/j.actbio.2022.05.018. Epub 2022 May 16. PMID: 35580827. 2: Qiu S, Jia Y, Sun Y, Han P, Xu J, Wen G, Chai Y. Von Hippel-Lindau (VHL) Protein Antagonist VH298 Improves Wound Healing in Streptozotocin-Induced Hyperglycaemic Rats by Activating Hypoxia-Inducible Factor- (HIF-) 1 Signalling. J Diabetes Res. 2019 Feb 17;2019:1897174. doi: 10.1155/2019/1897174. PMID: 30911550; PMCID: PMC6398031. 3: Qiu S, Jia Y, Tang J, Liu X, Hu H, Wu T, Chai Y. Von Hippel-Lindau (VHL) protein antagonist, VH298, promotes functional activities of tendon-derived stem cells and accelerates healing of entheses in rats by inhibiting ubiquitination of hydroxy-HIF-1α. Biochem Biophys Res Commun. 2018 Nov 10;505(4):1063-1069. doi: 10.1016/j.bbrc.2018.09.172. Epub 2018 Oct 9. PMID: 30314704. 4: Soares P, Gadd MS, Frost J, Galdeano C, Ellis L, Epemolu O, Rocha S, Read KD, Ciulli A. Group-Based Optimization of Potent and Cell-Active Inhibitors of the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase: Structure-Activity Relationships Leading to the Chemical Probe (2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)- 3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2- carboxamide (VH298). J Med Chem. 2018 Jan 25;61(2):599-618. doi: 10.1021/acs.jmedchem.7b00675. Epub 2017 Sep 18. PMID: 28853884; PMCID: PMC5788404. 5: Qin X, Wu K, Zuo C, Lin M. The Expression and Role of Hypoxia-induced Factor-1α in Human Tenon's Capsule Fibroblasts under Hypoxia. Curr Eye Res. 2021 Mar;46(3):417-425. doi: 10.1080/02713683.2020.1805470. Epub 2020 Sep 16. PMID: 32767899. 6: Frost J, Rocha S, Ciulli A. Von Hippel-Lindau (VHL) small-molecule inhibitor binding increases stability and intracellular levels of VHL protein. J Biol Chem. 2021 Aug;297(2):100910. doi: 10.1016/j.jbc.2021.100910. Epub 2021 Jun 24. PMID: 34174286; PMCID: PMC8313594. 7: Frost J, Galdeano C, Soares P, Gadd MS, Grzes KM, Ellis L, Epemolu O, Shimamura S, Bantscheff M, Grandi P, Read KD, Cantrell DA, Rocha S, Ciulli A. Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition. Nat Commun. 2016 Nov 4;7:13312. doi: 10.1038/ncomms13312. PMID: 27811928; PMCID: PMC5097156. 8: Tovell H, Testa A, Maniaci C, Zhou H, Prescott AR, Macartney T, Ciulli A, Alessi DR. Rapid and Reversible Knockdown of Endogenously Tagged Endosomal Proteins via an Optimized HaloPROTAC Degrader. ACS Chem Biol. 2019 May 17;14(5):882-892. doi: 10.1021/acschembio.8b01016. Epub 2019 Apr 22. PMID: 30978004; PMCID: PMC6528276. 9: Frost J, Ciulli A, Rocha S. RNA-seq analysis of PHD and VHL inhibitors reveals differences and similarities to the hypoxia response. Wellcome Open Res. 2019 Jan 29;4:17. doi: 10.12688/wellcomeopenres.15044.1. PMID: 30801039; PMCID: PMC6376255. 10: Zhang Q, Wang L, Jiang J, Lin S, Luo A, Zhao P, Tan W, Zhang M. Critical Role of AdipoR1 in Regulating Th17 Cell Differentiation Through Modulation of HIF-1α-Dependent Glycolysis. Front Immunol. 2020 Aug 18;11:2040. doi: 10.3389/fimmu.2020.02040. PMID: 32973810; PMCID: PMC7461876.