Emixustat HCl
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MedKoo CAT#: 319694

CAS#: 1141934-97-5 (HCl)

Description: Emixustat, also known as ACU-4429, is a visual cycle modulator in development for the potential treatment of GA associated with dry AMD. Emixustat is a nonretinoid compound with a unique mode of action in the retinal pigment epithelium, where it modulates the biosynthesis of visual chromophore through its effect on retinal pigment epithelium-specific 65 kDa protein isomerase.

Chemical Structure

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Emixustat HCl
CAS# 1141934-97-5 (HCl)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 319694
Name: Emixustat HCl
CAS#: 1141934-97-5 (HCl)
Chemical Formula: C16H26ClNO2
Exact Mass: 0.00
Molecular Weight: 299.839
Elemental Analysis: C, 64.09; H, 8.74; Cl, 11.82; N, 4.67; O, 10.67

Price and Availability

Size Price Availability Quantity
5mg USD 450 2 Weeks
10mg USD 800 2 Weeks
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Related CAS #: 1141934-97-5 (HCl)   1141777-14-1 (free base)  

Synonym: ACU-4429; ACU 4429; ACU4429; ACU 4429 HCl; ACU 4429 hydrochloride; Emixustat; Emixustat HCl; Emixustat hydrochloride;

IUPAC/Chemical Name: (1R)-3-Amino-1-(3-(cyclohexylmethoxy)phenyl)propan-1-ol hydrochloride

InChi Key: BPZWRYOUJMDQSY-PKLMIRHRSA-N

InChi Code: InChI=1S/C16H25NO2.ClH/c17-10-9-16(18)14-7-4-8-15(11-14)19-12-13-5-2-1-3-6-13;/h4,7-8,11,13,16,18H,1-3,5-6,9-10,12,17H2;1H/t16-;/m1./s1

SMILES Code: O[C@@H](C1=CC=CC(OCC2CCCCC2)=C1)CCN.[H]Cl

Appearance: Solid powder

Purity: >98% (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, not in water

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
Instruction:
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Biological target: Emixustat hydrochloride strongly inhibits 11-cis-retinol production with IC50 values of 232 ± 3 nM.
In vitro activity: The production 11-cis-retinol (11-cis-ROL) was measured by HPLC (Fig 2A). The data showed a concentration-dependent reduction of 11-cis-ROL production (i.e., inhibition of RPE65 isomerase activity) by emixustat. Reference: PLoS One. 2015; 10(5): e0124940. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430241/
In vivo activity: In vehicle-treated animals, cation channel activity increased in the dark. Emixustat treatment reduced cation channel activity; activity was comparable to vehicle-treated controls in light conditions. In vehicle-treated rats, minimum retinal oxygen tension decreased as the retina recovered from a photobleach, indicating that more oxygen was being consumed. Emixustat treatment prevented the decrease in oxygen pressure after photobleach. Reference: Invest Ophthalmol Vis Sci. 2019 Nov 1;60(14):4924-4930. https://pubmed.ncbi.nlm.nih.gov/31770432/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 44.0 146.75

Preparing Stock Solutions

The following data is based on the product molecular weight 299.84 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.

Recalculate based on batch purity %
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. Bavik C, Henry SH, Zhang Y, Mitts K, McGinn T, Budzynski E, Pashko A, Lieu KL, Zhong S, Blumberg B, Kuksa V, Orme M, Scott I, Fawzi A, Kubota R. 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. Kubota R, Calkins DJ, Henry SH, Linsenmeier RA. Emixustat Reduces Metabolic Demand of Dark Activity in the Retina. Invest Ophthalmol Vis Sci. 2019 Nov 1;60(14):4924-4930. doi: 10.1167/iovs.19-28194. PMID: 31770432. 3. Zhang J, Kiser PD, Badiee M, Palczewska G, Dong Z, Golczak M, Tochtrop GP, Palczewski K. Molecular pharmacodynamics of emixustat in protection against retinal degeneration. J Clin Invest. 2015 Jul 1;125(7):2781-94. doi: 10.1172/JCI80950. Epub 2015 Jun 15. PMID: 26075817; PMCID: PMC4563688.
In vitro protocol: 1. Bavik C, Henry SH, Zhang Y, Mitts K, McGinn T, Budzynski E, Pashko A, Lieu KL, Zhong S, Blumberg B, Kuksa V, Orme M, Scott I, Fawzi A, Kubota R. 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.
In vivo protocol: 1. Kubota R, Calkins DJ, Henry SH, Linsenmeier RA. Emixustat Reduces Metabolic Demand of Dark Activity in the Retina. Invest Ophthalmol Vis Sci. 2019 Nov 1;60(14):4924-4930. doi: 10.1167/iovs.19-28194. PMID: 31770432. 2. Zhang J, Kiser PD, Badiee M, Palczewska G, Dong Z, Golczak M, Tochtrop GP, Palczewski K. Molecular pharmacodynamics of emixustat in protection against retinal degeneration. J Clin Invest. 2015 Jul 1;125(7):2781-94. doi: 10.1172/JCI80950. Epub 2015 Jun 15. PMID: 26075817; PMCID: PMC4563688.

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1: Jack LS, Sadiq MA, Do DV, Nguyen QD. Emixustat and Lampalizumab: Potential Therapeutic Options for Geographic Atrophy. Dev Ophthalmol. 2016;55:302-9. doi: 10.1159/000438954. Epub 2015 Oct 26. PMID: 26501510.


2: Kubota R, Calkins DJ, Henry SH, Linsenmeier RA. Emixustat Reduces Metabolic Demand of Dark Activity in the Retina. Invest Ophthalmol Vis Sci. 2019 Nov 1;60(14):4924-4930. doi: 10.1167/iovs.19-28194. PMID: 31770432.


3: Podoll T, Geisler L, Parys MV, Hanson G, Reid MJ. Validation and reproducibility of an LC-MS/MS method for emixustat and its three deaminated metabolites in human plasma. Bioanalysis. 2018 Nov 1;10(22):1803-1817. doi: 10.4155/bio-2018-0159. Epub 2018 Oct 16. PMID: 30325202.


4: Kubota R, Jhaveri C, Koester JM, Gregory JK. Effects of emixustat hydrochloride in patients with proliferative diabetic retinopathy: a randomized, placebo-controlled phase 2 study. Graefes Arch Clin Exp Ophthalmol. 2021 Feb;259(2):369-378. doi: 10.1007/s00417-020-04899-y. Epub 2020 Aug 27. PMID: 32852613; PMCID: PMC7843479.


5: Rosenfeld PJ, Dugel PU, Holz FG, Heier JS, Pearlman JA, Novack RL, Csaky KG, Koester JM, Gregory JK, Kubota R. Emixustat Hydrochloride for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Clinical Trial. Ophthalmology. 2018 Oct;125(10):1556-1567. doi: 10.1016/j.ophtha.2018.03.059. Epub 2018 Apr 30. Erratum in: Ophthalmology. 2019 Mar;126(3):471-472. PMID: 29716784.


6: Reid MJ, Eyre R, Podoll T. Oxidative Deamination of Emixustat by Human Vascular Adhesion Protein-1/Semicarbazide-Sensitive Amine Oxidase. Drug Metab Dispos. 2019 May;47(5):504-515. doi: 10.1124/dmd.118.085811. Epub 2019 Feb 20. PMID: 30787099.


7: Fitzsimmons ME, Sun G, Kuksa V, Reid MJ. Disposition, profiling and identification of emixustat and its metabolites in humans. Xenobiotica. 2018 Jun;48(6):592-604. doi: 10.1080/00498254.2017.1350889. Epub 2017 Jul 28. PMID: 28678597.


8: Zhang J, Kiser PD, Badiee M, Palczewska G, Dong Z, Golczak M, Tochtrop GP, Palczewski K. Molecular pharmacodynamics of emixustat in protection against retinal degeneration. J Clin Invest. 2015 Jul 1;125(7):2781-94. doi: 10.1172/JCI80950. Epub 2015 Jun 15. PMID: 26075817; PMCID: PMC4563688.


9: Kubota R, Birch DG, Gregory JK, Koester JM. Randomised study evaluating the pharmacodynamics of emixustat hydrochloride in subjects with macular atrophy secondary to Stargardt disease. Br J Ophthalmol. 2022 Mar;106(3):403-408. doi: 10.1136/bjophthalmol-2020-317712. Epub 2020 Nov 19. PMID: 33214244; PMCID: PMC8867285.


10: Miao Z, Farnham JG, Hanson G, Podoll T, Reid MJ. Bioanalysis of emixustat (ACU-4429) in whole blood collected with volumetric absorptive microsampling by LC-MS/MS. Bioanalysis. 2015;7(16):2071-83. doi: 10.4155/bio.15.125. PMID: 26327186.


11: Kubota R, Al-Fayoumi S, Mallikaarjun S, Patil S, Bavik C, Chandler JW. 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.


12: Blum E, Zhang J, Zaluski J, Einstein DE, Korshin EE, Kubas A, Gruzman A, Tochtrop GP, Kiser PD, Palczewski K. Rational Alteration of Pharmacokinetics of Chiral Fluorinated and Deuterated Derivatives of Emixustat for Retinal Therapy. J Med Chem. 2021 Jun 24;64(12):8287-8302. doi: 10.1021/acs.jmedchem.1c00279. Epub 2021 Jun 3. PMID: 34081480; PMCID: PMC8381290.


13: Kubota R, Gregory J, Henry S, Mata NL. Pharmacotherapy for metabolic and cellular stress in degenerative retinal diseases. Drug Discov Today. 2020 Feb;25(2):292-304. doi: 10.1016/j.drudis.2019.11.013. Epub 2019 Dec 3. PMID: 31809750.


14: Blum E, Zhang J, Korshin E, Palczewski K, Gruzman A. Development of chiral fluorinated alkyl derivatives of emixustat as drug candidates for the treatment of retinal degenerative diseases. Bioorg Med Chem Lett. 2020 Sep 15;30(18):127421. doi: 10.1016/j.bmcl.2020.127421. Epub 2020 Jul 18. PMID: 32717613; PMCID: PMC7494577.


15: Dugel PU, Novack RL, Csaky KG, Richmond PP, Birch DG, Kubota R. Phase ii, randomized, placebo-controlled, 90-day study of emixustat hydrochloride in geographic atrophy associated with dry age-related macular degeneration. Retina. 2015 Jun;35(6):1173-83. doi: 10.1097/IAE.0000000000000606. PMID: 25932553; PMCID: PMC4452434.


16: Bavik C, Henry SH, Zhang Y, Mitts K, McGinn T, Budzynski E, Pashko A, Lieu KL, Zhong S, Blumberg B, Kuksa V, Orme M, Scott I, Fawzi A, Kubota R. 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.


17: Hussain RM, Ciulla TA, Berrocal AM, Gregori NZ, Flynn HW Jr, Lam BL. Stargardt macular dystrophy and evolving therapies. Expert Opin Biol Ther. 2018 Oct;18(10):1049-1059. doi: 10.1080/14712598.2018.1513486. Epub 2018 Sep 10. PMID: 30129371.


18: Hussain RM, Gregori NZ, Ciulla TA, Lam BL. Pharmacotherapy of retinal disease with visual cycle modulators. Expert Opin Pharmacother. 2018 Apr;19(5):471-481. doi: 10.1080/14656566.2018.1448060. Epub 2018 Mar 15. PMID: 29542350.


19: Kiser PD, Zhang J, Badiee M, Kinoshita J, Peachey NS, Tochtrop GP, Palczewski K. Rational Tuning of Visual Cycle Modulator Pharmacodynamics. J Pharmacol Exp Ther. 2017 Jul;362(1):131-145. doi: 10.1124/jpet.117.240721. Epub 2017 May 5. PMID: 28476927; PMCID: PMC5490204.


20: Dreffs A, Lin CM, Liu X, Shanmugam S, Abcouwer SF, Kern TS, Antonetti DA. 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.