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Purity: =98.62%
2BAct is a novel, potent, highly selective, CNS-permeable, and orally bioactive eif2b (eukaryotic initiation factor 2B) activator with an EC50 of 33 nM, it prevents neurological defects caused by a chronic integrated stress response (ISR). The transcriptome and proteome of Vanishing White Matter (VWM) mice return to normal after receiving long-term 2BAct treatment, which also prevents all pathological indicators. The maladaptive stress response is eliminated in vivo by 2BAct, which increases the mutant eIF2B complex's residual activity. Therefore, 2BAct-like molecules may offer a viable therapeutic strategy for VWM and offer relief from the induction of chronic ISR in a range of disease contexts.
Targets |
eIF2
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ln Vitro |
Primary-generated fibrous voids from R191H exhibit a threefold increase in 2BAct activity (EC50=7.3 nM) and a lower GEF activity than WT voids [1].
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ln Vivo |
2BAct (300 μg 2BAct/g food; 21 weeks) normalizes body weight growth in VWM mice [1]. 2BAct protects motor impairments, myelin loss, and reactive neural network insomnia in VWM [1]. Residual activity of 2BAct in the near-term eIF2B complex removes maladaptive near-term responses [1].
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References |
[1]. Wong YL, et al. eIF2B activator prevents neurological defects caused by a chronic integrated stress response. Elife. 2019;8:e42940. Published 2019 Jan 9.
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Molecular Formula |
C19H16CLF3N4O3
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Molecular Weight |
440.803553581238
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Exact Mass |
440.09
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Elemental Analysis |
C, 51.77; H, 3.66; Cl, 8.04; F, 12.93; N, 12.71; O, 10.89
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CAS # |
2143542-28-1
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Related CAS # |
2143542-28-1
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Appearance |
Solid powder
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SMILES |
C1C2(CC1(C2)NC(=O)C3=NC=C(N=C3)C(F)F)NC(=O)COC4=CC(=C(C=C4)Cl)F
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InChi Key |
HYQJXXCYOYRNMP-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C19H16ClF3N4O3/c20-11-2-1-10(3-12(11)21)30-6-15(28)26-18-7-19(8-18,9-18)27-17(29)14-5-24-13(4-25-14)16(22)23/h1-5,16H,6-9H2,(H,26,28)(H,27,29)
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Chemical Name |
N-[3-[[2-(4-chloro-3-fluorophenoxy)acetyl]amino]-1-bicyclo[1.1.1]pentanyl]-5-(difluoromethyl)pyrazine-2-carboxamide
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Synonyms |
2BAct; 2B Act; 2B-Act
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO: ~250 mg/mL (~567.2 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.72 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.72 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.2686 mL | 11.3430 mL | 22.6860 mL | |
5 mM | 0.4537 mL | 2.2686 mL | 4.5372 mL | |
10 mM | 0.2269 mL | 1.1343 mL | 2.2686 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
2BAct is an eIF2B activator with similar potency to ISRIB. Elife . 2019 Jan 9:8:e42940. td> |
2BAct normalized body weight gain and prevented motor deficits in female R191H mice. Elife . 2019 Jan 9:8:e42940. td> |
The ISR is activated in the brain of R191H mice and its induction is prevented by 2BAct. Elife . 2019 Jan 9:8:e42940. td> |