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MedKoo Cat#: 326929 | Name: Ranirestat
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Ranirestat, also known as AS-3201 and SX-3201, is an aldose reductase inhibitor being developed for the treatment of diabetic neuropathy.

Chemical Structure

Ranirestat
Ranirestat
CAS#147254-64-6

Theoretical Analysis

MedKoo Cat#: 326929

Name: Ranirestat

CAS#: 147254-64-6

Chemical Formula: C17H11BrFN3O4

Exact Mass: 418.9917

Molecular Weight: 420.19

Elemental Analysis: C, 48.59; H, 2.64; Br, 19.02; F, 4.52; N, 10.00; O, 15.23

Price and Availability

Size Price Availability Quantity
5mg USD 350.00
10mg USD 650.00
25mg USD 1,250.00
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Related CAS #
No Data
Synonym
AS-3201; AS3201; AS 3201; SX-3201; SX3201; SX 3201; Ranirestat.
IUPAC/Chemical Name
(R)-2'-(4-bromo-2-fluorobenzyl)-1'H-spiro[pyrrolidine-3,4'-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetraone
InChi Key
QCVNMNYRNIMDKV-QGZVFWFLSA-N
InChi Code
InChI=1S/C17H11BrFN3O4/c18-10-4-3-9(11(19)6-10)8-21-14(24)12-2-1-5-22(12)17(16(21)26)7-13(23)20-15(17)25/h1-6H,7-8H2,(H,20,23,25)/t17-/m1/s1
SMILES Code
O=C(N(CC1=CC=C(Br)C=C1F)C2=O)C3=CC=CN3[C@]2(C4)C(NC4=O)=O
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
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
Certificate of Analysis
View CoA: current batch, Lot#S20G01M31
Safety Data Sheet (SDS)
View Safety Data Sheet (SDS)
Instruction
View handling instruction
Biological target:
Ranirestat is a potent and orally active aldose reductase inhibitor with IC50s of 11 nM and 15 nM for rat lens AR and recombinant human AR, respectively, and a Ki of 0.38 nM for recombinant human AR.
In vitro activity:
The findings of this study show that UGT2B, a UDP-glucuronosyltransferases isoform, specifically utilizes UDP-glucose but not UDP-glucuronic acid as a sugar donor for the conjugation of AS-3201 in human liver microsomes. Reference: Biochem Pharmacol. 2004 Apr 1;67(7):1269-78. https://pubmed.ncbi.nlm.nih.gov/15013842/
In vivo activity:
Ranirestat improved the peripheral nervous dysfunctions in rats with advanced diabetic polyneuropathy. Ranirestat could have potential for regeneration in the peripheral nervous system of diabetic rats. Reference: J Diabetes Res. 2019 Nov 18;2019:2756020. https://pubmed.ncbi.nlm.nih.gov/31828158/
Solvent mg/mL mM
Solubility
DMSO 20.0 47.60
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 420.19 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. Toide K, Terauchi Y, Fujii T, Yamazaki H, Kamataki T. Uridine diphosphate sugar-selective conjugation of an aldose reductase inhibitor (AS-3201) by UDP-glucuronosyltransferase 2B subfamily in human liver microsomes. Biochem Pharmacol. 2004 Apr 1;67(7):1269-78. doi: 10.1016/j.bcp.2003.11.010. PMID: 15013842. 2. Negoro T, Murata M, Ueda S, Fujitani B, Ono Y, Kuromiya A, Komiya M, Suzuki K, Matsumoto J. Novel, highly potent aldose reductase inhibitors: (R)-(-)-2-(4-bromo-2-fluorobenzyl)-1,2,3,4- tetrahydropyrrolo[1,2-a]pyrazine -4-spiro-3'-pyrrolidine-1,2',3,5'-tetrone (AS-3201) and its congeners. J Med Chem. 1998 Oct 8;41(21):4118-29. doi: 10.1021/jm9802968. PMID: 9767647. 3. Asano S, Himeno T, Hayami T, Motegi M, Inoue R, Nakai-Shimoda H, Miura-Yura E, Morishita Y, Kondo M, Tsunekawa S, Kato Y, Kato K, Naruse K, Nakamura J, Kamiya H. Ranirestat Improved Nerve Conduction Velocities, Sensory Perception, and Intraepidermal Nerve Fiber Density in Rats with Overt Diabetic Polyneuropathy. J Diabetes Res. 2019 Nov 18;2019:2756020. doi: 10.1155/2019/2756020. PMID: 31828158; PMCID: PMC6885776. 4. Sekiguchi K, Kohara N, Baba M, Komori T, Naito Y, Imai T, Satoh J, Yamaguchi Y, Hamatani T; Ranirestat Group. Aldose reductase inhibitor ranirestat significantly improves nerve conduction velocity in diabetic polyneuropathy: A randomized double-blind placebo-controlled study in Japan. J Diabetes Investig. 2019 Mar;10(2):466-474. doi: 10.1111/jdi.12890. Epub 2018 Aug 9. PMID: 29975462; PMCID: PMC6400176.
In vitro protocol:
1. Toide K, Terauchi Y, Fujii T, Yamazaki H, Kamataki T. Uridine diphosphate sugar-selective conjugation of an aldose reductase inhibitor (AS-3201) by UDP-glucuronosyltransferase 2B subfamily in human liver microsomes. Biochem Pharmacol. 2004 Apr 1;67(7):1269-78. doi: 10.1016/j.bcp.2003.11.010. PMID: 15013842. 2. Negoro T, Murata M, Ueda S, Fujitani B, Ono Y, Kuromiya A, Komiya M, Suzuki K, Matsumoto J. Novel, highly potent aldose reductase inhibitors: (R)-(-)-2-(4-bromo-2-fluorobenzyl)-1,2,3,4- tetrahydropyrrolo[1,2-a]pyrazine -4-spiro-3'-pyrrolidine-1,2',3,5'-tetrone (AS-3201) and its congeners. J Med Chem. 1998 Oct 8;41(21):4118-29. doi: 10.1021/jm9802968. PMID: 9767647.
In vivo protocol:
1. Asano S, Himeno T, Hayami T, Motegi M, Inoue R, Nakai-Shimoda H, Miura-Yura E, Morishita Y, Kondo M, Tsunekawa S, Kato Y, Kato K, Naruse K, Nakamura J, Kamiya H. Ranirestat Improved Nerve Conduction Velocities, Sensory Perception, and Intraepidermal Nerve Fiber Density in Rats with Overt Diabetic Polyneuropathy. J Diabetes Res. 2019 Nov 18;2019:2756020. doi: 10.1155/2019/2756020. PMID: 31828158; PMCID: PMC6885776. 2. Sekiguchi K, Kohara N, Baba M, Komori T, Naito Y, Imai T, Satoh J, Yamaguchi Y, Hamatani T; Ranirestat Group. Aldose reductase inhibitor ranirestat significantly improves nerve conduction velocity in diabetic polyneuropathy: A randomized double-blind placebo-controlled study in Japan. J Diabetes Investig. 2019 Mar;10(2):466-474. doi: 10.1111/jdi.12890. Epub 2018 Aug 9. PMID: 29975462; PMCID: PMC6400176.
1: Bajraktari-Sylejmani G, Oster JS, Burhenne J, Haefeli WE, Sauter M, Weiss J. In vitro evaluation of the reductive carbonyl idarubicin metabolism to evaluate inhibitors of the formation of cardiotoxic idarubicinol via carbonyl and aldo- keto reductases. Arch Toxicol. 2024 Mar;98(3):807-820. doi: 10.1007/s00204-023-03661-7. Epub 2024 Jan 4. PMID: 38175295; PMCID: PMC10861747. 2: Balogun FO, Singh K, Rampadarath A, Akoonjee A, Naidoo K, Sabiu S. Cheminformatics identification of modulators of key carbohydrate-metabolizing enzymes from C. cujete for type-2 diabetes mellitus intervention. J Diabetes Metab Disord. 2023 Jul 1;22(2):1299-1317. doi: 10.1007/s40200-023-01249-7. PMID: 37969920; PMCID: PMC10638353. 3: Dutta D, Mohindra R, Kumar M, Kumar A, Sharma M. Ranirestat Improves Electrophysiologic but not Clinical Measures of Diabetic Polyneuropathy: A Meta- Analysis. Indian J Endocrinol Metab. 2022 Sep-Oct;26(5):399-406. doi: 10.4103/ijem.ijem_242_22. Epub 2022 Nov 22. PMID: 36618527; PMCID: PMC9815196. 4: Yako H, Niimi N, Kato A, Takaku S, Tatsumi Y, Nishito Y, Kato K, Sango K. Role of pyruvate in maintaining cell viability and energy production under high- glucose conditions. Sci Rep. 2021 Sep 23;11(1):18910. doi: 10.1038/s41598-021-98082-w. PMID: 34556698; PMCID: PMC8460646. 5: Joshi MB, Ahamed R, Hegde M, Nair AS, Ramachandra L, Satyamoorthy K. Glucose induces metabolic reprogramming in neutrophils during type 2 diabetes to form constitutive extracellular traps and decreased responsiveness to lipopolysaccharides. Biochim Biophys Acta Mol Basis Dis. 2020 Dec 1;1866(12):165940. doi: 10.1016/j.bbadis.2020.165940. Epub 2020 Aug 20. PMID: 32827651. 6: Itou M, Fujita T, Inoue K, Uchida N, Takagaki T, Ishii D, Kakuyama H. Pharmacokinetics and Safety of Ranirestat in Patients With Hepatic Impairment. J Clin Pharmacol. 2020 Oct;60(10):1397-1403. doi: 10.1002/jcph.1636. Epub 2020 May 21. PMID: 32437025. 7: Asano S, Himeno T, Hayami T, Motegi M, Inoue R, Nakai-Shimoda H, Miura-Yura E, Morishita Y, Kondo M, Tsunekawa S, Kato Y, Kato K, Naruse K, Nakamura J, Kamiya H. Ranirestat Improved Nerve Conduction Velocities, Sensory Perception, and Intraepidermal Nerve Fiber Density in Rats with Overt Diabetic Polyneuropathy. J Diabetes Res. 2019 Nov 18;2019:2756020. doi: 10.1155/2019/2756020. PMID: 31828158; PMCID: PMC6885776. 8: Yamamura ET, Tsuzaki K, Kita S. A novel method of producing the key intermediate ASI-2 of ranirestat using a porcine liver esterase (PLE) substitute enzyme. Biosci Biotechnol Biochem. 2019 Jun;83(6):1124-1135. doi: 10.1080/09168451.2019.1580139. Epub 2019 Feb 20. PMID: 30782084. 9: Sekiguchi K, Kohara N, Baba M, Komori T, Naito Y, Imai T, Satoh J, Yamaguchi Y, Hamatani T; Ranirestat Group. Aldose reductase inhibitor ranirestat significantly improves nerve conduction velocity in diabetic polyneuropathy: A randomized double-blind placebo-controlled study in Japan. J Diabetes Investig. 2019 Mar;10(2):466-474. doi: 10.1111/jdi.12890. Epub 2018 Aug 9. PMID: 29975462; PMCID: PMC6400176. 10: Ishibashi Y, Matsui T, Matsumoto T, Kato H, Yamagishi S. Ranirestat has a stronger inhibitory activity on aldose reductase and suppresses inflammatory reactions in high glucose-exposed endothelial cells. Diab Vasc Dis Res. 2016 Jul;13(4):312-5. doi: 10.1177/1479164116640220. Epub 2016 Apr 29. PMID: 27190083. 11: Miyoshi A, Yamada M, Shida H, Nakazawa D, Kusunoki Y, Nakamura A, Miyoshi H, Tomaru U, Atsumi T, Ishizu A. Circulating Neutrophil Extracellular Trap Levels in Well-Controlled Type 2 Diabetes and Pathway Involved in Their Formation Induced by High-Dose Glucose. Pathobiology. 2016;83(5):243-51. doi: 10.1159/000444881. Epub 2016 May 18. PMID: 27189166. 12: Satoh J, Kohara N, Sekiguchi K, Yamaguchi Y. Effect of Ranirestat on Sensory and Motor Nerve Function in Japanese Patients with Diabetic Polyneuropathy: A Randomized Double-Blind Placebo-Controlled Study. J Diabetes Res. 2016;2016:5383797. doi: 10.1155/2016/5383797. Epub 2016 Jan 10. PMID: 26881251; PMCID: PMC4736957. 13: Antony P, Vijayan R. Identification of Novel Aldose Reductase Inhibitors from Spices: A Molecular Docking and Simulation Study. PLoS One. 2015 Sep 18;10(9):e0138186. doi: 10.1371/journal.pone.0138186. PMID: 26384019; PMCID: PMC4575143. 14: Grewal AS, Bhardwaj S, Pandita D, Lather V, Sekhon BS. Updates on Aldose Reductase Inhibitors for Management of Diabetic Complications and Non-diabetic Diseases. Mini Rev Med Chem. 2016;16(2):120-62. doi: 10.2174/1389557515666150909143737. PMID: 26349493. 15: Polydefkis M, Arezzo J, Nash M, Bril V, Shaibani A, Gordon RJ, Bradshaw KL, Junor RW; Ranirestat Study Group. Safety and efficacy of ranirestat in patients with mild-to-moderate diabetic sensorimotor polyneuropathy. J Peripher Nerv Syst. 2015 Dec;20(4):363-71. doi: 10.1111/jns.12138. PMID: 26313450. 16: Toyoda F, Tanaka Y, Ota A, Shimmura M, Kinoshita N, Takano H, Matsumoto T, Tsuji J, Kakehashi A. Effect of ranirestat, a new aldose reductase inhibitor, on diabetic retinopathy in SDT rats. J Diabetes Res. 2014;2014:672590. doi: 10.1155/2014/672590. Epub 2014 Aug 25. PMID: 25215304; PMCID: PMC4158328. 17: Giannoukakis N. Evaluation of ranirestat for the treatment of diabetic neuropathy. Expert Opin Drug Metab Toxicol. 2014 Jul;10(7):1051-9. doi: 10.1517/17425255.2014.916277. Epub 2014 Apr 30. PMID: 24785785. 18: Kadam A, Dawane B, Pawar M, Shegokar H, Patil K, Meshram R, Gacche R. Development of novel pyrazolone derivatives as inhibitors of aldose reductase: an eco-friendly one-pot synthesis, experimental screening and in silico analysis. Bioorg Chem. 2014 Apr;53:67-74. doi: 10.1016/j.bioorg.2014.02.002. Epub 2014 Feb 19. PMID: 24607578. 19: Hosseini A, Abdollahi M. Diabetic neuropathy and oxidative stress: therapeutic perspectives. Oxid Med Cell Longev. 2013;2013:168039. doi: 10.1155/2013/168039. Epub 2013 Apr 24. PMID: 23738033; PMCID: PMC3655656. 20: Ota A, Kakehashi A, Toyoda F, Kinoshita N, Shinmura M, Takano H, Obata H, Matsumoto T, Tsuji J, Dobashi Y, Fujimoto WY, Kawakami M, Kanazawa Y. Effects of long-term treatment with ranirestat, a potent aldose reductase inhibitor, on diabetic cataract and neuropathy in spontaneously diabetic torii rats. J Diabetes Res. 2013;2013:175901. doi: 10.1155/2013/175901. Epub 2013 Mar 13. PMID: 23671855; PMCID: PMC3647549.