EXH

 CAS No.: 2211116-16-2  Cat No.: BP-200039 4.5  

EXH is a potent and versatile E3 ligase ligand utilized in the design and development of PROTACs (Proteolysis Targeting Chimeras). As a critical component in targeted protein degradation research, EXH binds selectively to the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex, enabling researchers to recruit VHL for the ubiquitination and subsequent degradation of disease-relevant target proteins. This VHL ligand is frequently employed in constructing bifunctional molecules for therapeutic and research applications, promoting innovative solutions in cancer, neurodegenerative, and other proteinopathy-centered studies. Ideal for medicinal chemistry and drug discovery projects, EXH provides researchers with a robust tool for advancing next-generation protein degradation technologies.

EXH

Structure of 2211116-16-2

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Ligand for E3 Ligase
Molecular Formula
C24H31FN4O4S
Molecular Weight
490.59

* For research and manufacturing use only. Not for human or clinical use.

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Popular Publications Citing BOC Sciences Products
IUPACName
(2R,3R,4S)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-3-fluoro-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
Boiling Point
784.7±60.0 °C at 760 mmHg
Density
1.30±0.1 g/cm3
InChI Key
MNNVXLLCYGGFOQ-VNYTWHDVSA-N
InChI
InChI=1S/C24H31FN4O4S/c1-13-20(34-12-27-13)16-8-6-15(7-9-16)10-26-22(32)19-18(25)17(31)11-29(19)23(33)21(24(3,4)5)28-14(2)30/h6-9,12,17-19,21,31H,10-11H2,1-5H3,(H,26,32)(H,28,30)/t17-,18-,19-,21+/m0/s1
Canonical SMILES
CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)C3C(C(CN3C(=O)C(C(C)(C)C)NC(=O)C)O)F

Background Introduction

EXH is a next-generation ligand designed specifically for E3 ubiquitin ligase engagement, playing a pivotal role in the development of advanced PROTACs (Proteolysis Targeting Chimeras). E3 ligase ligands, such as EXH, enable researchers and drug developers to harness the ubiquitin-proteasome system for targeted protein degradation. By facilitating the recruitment of a selected E3 ligase, EXH provides new opportunities for the chemical biology and pharmaceutical industries, especially in expanding the range of druggable proteins.

Mechanism

The mechanism of EXH centers on its high-affinity binding to a specific E3 ubiquitin ligase. Upon incorporation into a PROTAC molecule, EXH acts as the E3 ligase-recruiting moiety. It brings the fused E3 ligase into close proximity with a target protein, which is simultaneously bound by the PROTAC's target ligand. This proximity enables the transfer of ubiquitin molecules from the E2 enzyme to the target protein, flagging it for recognition and degradation by the 26S proteasome. The chemical design of EXH allows for efficient linker attachment, facilitating modular assembly into bifunctional degraders.

Applications

EXH is widely utilized in:

• PROTAC synthesis and optimization, especially in systems requiring E3 ligase engagement beyond conventional ligases like CRBN or VHL.
• Structure-activity relationship (SAR) studies to explore E3 ligase selectivity and degradation efficiency in different cellular models.
• Drug discovery pipelines focusing on targeted protein degradation for undruggable or resistant protein targets.
• Development of tool compounds for elucidating ubiquitin-proteasome system biology and mechanisms of E3 ligase-mediated substrate recognition.
• Customizable conjugation strategies in both academic and commercial research projects aiming to expand the chemistry of protein degradation.
• High-purity compound verified by HPLC, NMR, and LC-MS
• Consistent batch-to-batch reproducibility with complete QC documentation
• Supplied with COA, MSDS, and analytical data for traceability
• Reliable global shipping with stability-guaranteed packaging
• Dedicated technical support and optional custom synthesis service
• Demonstrates strong binding affinity to CRBN, VHL, or other E3 ligases
• Enables stable E3 ligase recruitment for targeted protein degradation
• High affinity for VHL E3 ligase enables efficient target protein ubiquitination and degradation.
• Optimized molecular structure facilitates seamless integration into custom PROTAC design workflows.
1. Voluntary muscle and motor cortical activation during progressive exercise and passively induced hyperthermia
Julien D Périard, Ryan J Christian, Wade L Knez, Sébastien Racinais Exp Physiol. 2014 Jan;99(1):136-48.doi: 10.1113/expphysiol.2013.074583.Epub 2013 Sep 13.
This study examined whether central fatigue was exacerbated by an increase in muscle contractile speed caused by passive hyperthermia (PaH) and whether exercise-induced hyperthermia (ExH) combined with related peripheral fatigue influenced this response. The ExH was induced by cycling at 60% of maximal oxygen uptake in 38°C conditions and the PaH by sitting in a 48°C climate chamber. Ten men performed brief (≈ 5 s) and sustained (30 s) maximal voluntary isometric contractions (MVCs) of the knee extensors at baseline (CON, ~37.1°C) and during moderate (MOD, ≈ 38.5°C) and severe (SEV, ~39.5°C) hyperthermia. Motor nerve and transcranial magnetic stimulation were used to assess voluntary muscle and cortical activation level, along with contractile properties. Brief MVC force decreased to a similar extent during SEV-ExH (-8%) and SEV-PaH (-6%; P < 0.05 versus CON). Sustained MVC force also decreased during MOD-ExH (-10%), SEV-ExH (-13%) and SEV-PaH (-7%; P < 0.01 versus CON). Motor nerve and cortical activation were reduced on reaching MOD (≈ 3%) and SEV (≈ 5%) ExH and PaH during the brief and sustained MVCs (P < 0.01 versus CON). Peak twitch force decreased on reaching SEV-ExH and SEV-PaH (P < 0.05 versus CON). Following transcranial magnetic stimulation, during the brief and sustained MVCs the peak muscle relaxation rate increased in ExH and PaH (P < 0.01 versus CON). The increase was greatest during the sustained contraction in SEV-PaH (P < 0.01), but this did not exacerbate central fatigue relative to ExH. These results indicate that during fatiguing cycling exercise in the heat, quadriceps peak relaxation rate increases. However, the centrally mediated rate of activation appears sufficient to overcome even the largest increase in muscle relaxation rate, seen during SEV-PaH.
2. Effect of acute severe hypoxia on peripheral fatigue and endurance capacity in healthy humans
Lee M Romer, Hans C Haverkamp, Markus Amann, Andrew T Lovering, David F Pegelow, Jerome A Dempsey Am J Physiol Regul Integr Comp Physiol. 2007 Jan;292(1):R598-606.doi: 10.1152/ajpregu.00269.2006.Epub 2006 Sep 7.
We hypothesized that severe hypoxia limits exercise performance via decreased contractility of limb locomotor muscles. Nine male subjects [mean +/- SE maximum O(2) uptake (Vo(2 max)) = 56.5 +/- 2.7 ml x kg(-1) x min(-1)] cycled at > or =90% Vo(2 max) to exhaustion in normoxia [NORM-EXH; inspired O(2) fraction (Fi(O(2))) = 0.21, arterial O(2) saturation (Sp(O(2))) = 93 +/- 1%] and hypoxia (HYPOX-EXH; Fi(O(2)) = 0.13, Sp(O(2)) = 76 +/- 1%). The subjects also exercised in normoxia for a time equal to that achieved in hypoxia (NORM-CTRL; Sp(O(2)) = 96 +/- 1%). Quadriceps twitch force, in response to supramaximal single (nonpotentiated and potentiated 1 Hz) and paired magnetic stimuli of the femoral nerve (10-100 Hz), was assessed pre- and at 2.5, 35, and 70 min postexercise. Hypoxia exacerbated exercise-induced peripheral fatigue, as evidenced by a greater decrease in potentiated twitch force in HYPOX-EXH vs. NORM-CTRL (-39 +/- 4 vs. -24 +/- 3%, P < 0.01). Time to exhaustion was reduced by more than two-thirds in HYPOX-EXH vs. NORM-EXH (4.2 +/- 0.5 vs. 13.4 +/- 0.8 min, P < 0.01); however, peripheral fatigue was not different in HYPOX-EXH vs. NORM-EXH (-34 +/- 4 vs. -39 +/- 4%, P > 0.05). Blood lactate concentration and perceptions of limb discomfort were higher throughout HYPOX-EXH vs. NORM-CTRL but were not different at end-exercise in HYPOX-EXH vs. NORM-EXH. We conclude that severe hypoxia exacerbates peripheral fatigue of limb locomotor muscles and that this effect may contribute, in part, to the early termination of exercise.
3. Effects of morning versus evening combined strength and endurance training on physical performance, muscle hypertrophy, and serum hormone concentrations
Maria Küüsmaa, Moritz Schumann, Milan Sedliak, William J Kraemer, Robert U Newton, Jari-Pekka Malinen, Kai Nyman, Arja Häkkinen, Keijo Häkkinen Appl Physiol Nutr Metab. 2016 Dec;41(12):1285-1294.doi: 10.1139/apnm-2016-0271.
This study investigated the effects of 24 weeks of morning versus evening same-session combined strength (S) and endurance (E) training on physical performance, muscle hypertrophy, and resting serum testosterone and cortisol diurnal concentrations. Forty-two young men were matched and assigned to a morning (m) or evening (e) E + S or S + E group (mE + S, n = 9; mS + E, n = 9; eE + S, n = 12; and eS + E, n = 12). Participants were tested for dynamic leg press 1-repetition maximum (1RM) and time to exhaustion (Texh) during an incremental cycle ergometer test both in the morning and evening, cross-sectional area (CSA) of vastus lateralis and diurnal serum testosterone and cortisol concentrations (0730 h; 0930 h; 1630 h; 1830 h). All groups similarly increased 1RM in the morning (14%-19%; p < 0.001) and evening (18%-24%; p < 0.001). CSA increased in all groups by week 24 (12%-20%, p < 0.01); however, during the training weeks 13-24 the evening groups gained more muscle mass (time-of-day main effect; p < 0.05). Texh increased in all groups in the morning (16%-28%; p < 0.01) and evening (18%-27%; p < 0.001), however, a main effect for the exercise order, in favor of E + S, was observed on both testing times (p < 0.051). Diurnal rhythms in testosterone and cortisol remained statistically unaltered by the training order or time. The present results indicate that combined strength and endurance training in the evening may lead to larger gains in muscle mass, while the E + S training order might be more beneficial for endurance performance development. However, training order and time seem to influence the magnitude of adaptations only when the training period exceeded 12 weeks.

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Tip: Chemical formula is case sensitive. C22H30N4O c22h30n40
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