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Merck
CN

SML4012

Sigma-Aldrich

VHL Binder 30

≥97% (HPLC)

Synonym(s):

(2S,4R)-1-((S)-2-(1-Fluorocyclopropane-1-carboxamido)-3,3-di-methylbutanoyl)-4-hydroxy-N-((S)-1-(2-methyl-4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide, VHL Binder Compound 30, von Hippel−Lindau (VHL) Inhibitor Compound 30

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About This Item

Empirical Formula (Hill Notation):
C28H37FN4O4S
CAS Number:
Molecular Weight:
544.68
UNSPSC Code:
12352200
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Quality Level

Assay

≥97% (HPLC)

form

powder

color

white to beige

solubility

DMSO: 2 mg/mL, clear

storage temp.

-10 to -25°C

SMILES string

C[C@H](NC([C@@H]1C[C@@H](O)CN1C([C@@H](NC(C2(F)CC2)=O)C(C)(C)C)=O)=O)C3=C(C=C(C=C3)C4=C(N=CS4)C)C

InChI

1S/C28H37FN4O4S/c1-15-11-18(22-17(3)30-14-38-22)7-8-20(15)16(2)31-24(35)21-12-19(34)13-33(21)25(36)23(27(4,5)6)32-26(37)28(29)9-10-28/h7-8,11,14,16,19,21,23,34H,9-10,12-13H2,1-6H3,(H,31,35)(H,32,37)/t16-,19+,21-,23+/m0/s1

InChI key

NBHYPBDUODSQHJ-DTPUHQDNSA-N

Biochem/physiol Actions

Binds to the VHL protein with high-affinity and efficiently disrupts VHL-HIF-α interaction.



VHL Binder 30 (VHL Binder, Compound 30) is a highly potent, efficacious von Hippel−Lindau (VHL) E3 ubiquitin ligase binder with greater cell permeability, higher binding affinity (Kd = 37 & 25 nM by fluorescence polarization and surface plasmon resonance, respectively) and superior ability to induce Hypoxia-inducible factor-1α (HIF-1α) transcriptional activity (% of HIF-1α stabilization levels at 50 µM for 2 hr = 182 & 224 in HeLa & HEK293 cells; HIF-1α-OH stabilization at 50 µM for 2 hr = 263, 208 in HeLa & HEK293 cells, respectively; VH298 as the reference ligand VH298).

Storage Class Code

11 - Combustible Solids

WGK

WGK 3

Flash Point(F)

Not applicable

Flash Point(C)

Not applicable

Regulatory Information

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Lan Phuong Vu et al.
Journal of medicinal chemistry, 66(18), 12776-12811 (2023-09-14)
Hypoxia-inducible factor-1α (HIF-1α) constitutes the principal mediator of cellular adaptation to hypoxia in humans. The HIF-1α protein level and activity are tightly regulated by the ubiquitin E3 ligase von Hippel-Lindau (VHL). Here, we performed a structure-guided and bioactivity-driven design of

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