Emixustat (ACU-4429) (Synonyms: ACU-4429) |
رقم الكتالوجGC31373 |
Emixustat (ACU-4429) ، مُعدِّل دورة بصري جديد ، هو مثبط لإيزوميراز الدورة المرئية بقيمة IC50 تبلغ 4.4 نانومتر في المختبر.
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Cas No.: 1141777-14-1
Sample solution is provided at 25 µL, 10mM.
Emixustat(ACU-4429) is a first in class small-molecule visual cycle modulator that inhibits the isomerase complex. As an inhibitor of visual cycle isomerase, the IC50 value is 4.4 nM[1].
Emixustat strongly inhibits 11-cis-retinol production with an IC50 value of 232±3 nM[2]. A concentration-dependent reduction of 11-cis-ROL production (i.e., inhibition of RPE65 isomerase activity) by emixustat(10-5 to 10-10 M)[1].
Emixustat(0.01-3.0 mg/kg; p.o) was found to reduce the production of visual chromophore (11-cis retinal) in wild-type mice following a single oral dose (ED50 = 0.18 mg/kg) [1]. In 40 subjects (mean age, 38 years) Emixustat (n = 30) (5, 10, 20, 30, or 40 mg; 14-day) was rapidly absorbed (median T(max), 3.0-5 hours) and readily eliminated (mean t(1/2), 4.6-7.9 hours), and mean C(max) generally increased in proportion to dose. Systemic adverse events were minimal[3]. Emixustat significantly abates permeability after Ischemia Reperfusion(IR) on vascular permeability in mice[4].
References:
[1]. Bavik C, Henry SH, et,al.Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity. PLoS One. 2015 May 13;10(5):e0124940. doi: 10.1371/journal.pone.0124940. PMID: 25970164; PMCID: PMC4430241.
[2]. Kiser PD, Zhang J, et,al.Catalytic mechanism of a retinoid isomerase essential for vertebrate vision. Nat Chem Biol. 2015 Jun;11(6):409-15. doi: 10.1038/nchembio.1799. Epub 2015 Apr 20. PMID: 25894083; PMCID: PMC4433804.
[3].Kubota R, Al-Fayoumi S, et,al. Phase 1, dose-ranging study of emixustat hydrochloride (ACU-4429), a novel visual cycle modulator, in healthy volunteers. Retina. 2014 Mar;34(3):603-9. doi: 10.1097/01.iae.0000434565.80060.f8. PMID: 24056528.
[4].Dreffs A, Lin CM, et,al. All-trans-Retinaldehyde Contributes to Retinal Vascular Permeability in Ischemia Reperfusion. Invest Ophthalmol Vis Sci. 2020 Jun 3;61(6):8. doi: 10.1167/iovs.61.6.8. PMID: 32492112; PMCID: PMC7415894.
Animal experiment [1]: |
|
Animal models |
BALB/c mice (8 weeks) |
Preparation method |
Dark-adapted (12 hours) BALB/c mice (8 weeks, n = 4/group) were orally dosed with emixustat (0.01-3.0 mg/kg) or vehicle (water). At 4 hours post-dose, animals were photobleached (5000 lux white light, 10 min) without anesthesia or mydriatics, returned to the dark for 2 hours, and then euthanized under red light. |
Dosage form |
0.01-3.0 mg/kg; p.o |
Applications |
Emixustat was found to reduce the production of visual chromophore (11-cis retinal) in wild-type mice following a single oral dose (ED50 = 0.18 mg/kg). |
References: [1]. Bavik C, Henry SH,et,al. Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity. PLoS One. 2015 May 13;10(5):e0124940. doi: 10.1371/journal.pone.0124940. PMID: 25970164; PMCID: PMC4430241. |
Cas No. | 1141777-14-1 | SDF | |
المرادفات | ACU-4429 | ||
Canonical SMILES | O[C@H](CCN)C1=CC(OCC2CCCCC2)=CC=C1 | ||
Formula | C16H25NO2 | M.Wt | 263.38 |
الذوبان | DMSO : ≥ 43 mg/mL (163.26 mM) | Storage | Store at -20°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
1 mM | 3.7968 mL | 18.984 mL | 37.968 mL |
5 mM | 0.7594 mL | 3.7968 mL | 7.5936 mL |
10 mM | 0.3797 mL | 1.8984 mL | 3.7968 mL |
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Quality Control & SDS
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- Purity: >98.50%
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