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MedKoo Cat#: 326958 | Name: Ruboxistaurin HCl
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Description:

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

Ruboxistaurin, also known as LY-333531, is a PKC beta inhibitor potentially for the treatment of diabetic nephropathy and diabetic macular edema. Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-β1/Smad and GRAP pathways. Ruboxistaurin reduces oxidative stress and attenuates left ventricular hypertrophy and dysfunction in rats with streptozotocin-induced diabetes. Ruboxistaurin inhibits retinal neovascularization via suppression of phosphorylation of ERK1/2 and Akt.

Chemical Structure

Ruboxistaurin HCl
Ruboxistaurin HCl
CAS#169939-93-9 (HCl)

Theoretical Analysis

MedKoo Cat#: 326958

Name: Ruboxistaurin HCl

CAS#: 169939-93-9 (HCl)

Chemical Formula: C28H29ClN4O3

Exact Mass: 0.0000

Molecular Weight: 505.02

Elemental Analysis: C, 66.59; H, 5.79; Cl, 7.02; N, 11.09; O, 9.50

Price and Availability

Size Price Availability Quantity
1mg USD 90.00 Ready to ship
5mg USD 250.00 Ready to ship
10mg USD 400.00 Ready to ship
25mg USD 750.00 Ready to ship
50mg USD 1,250.00 Ready to ship
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Related CAS #
169939-94-0 (free base) 202260-21-7 (mesylate hydrate) 169939-93-9 (HCl) 192050-59-2 (mesylate)
Synonym
Ruboxistaurin; Ruboxistaurin hydrochloride, LY-333531; LY333531; LY 333531.
IUPAC/Chemical Name
(12E,32E,7S)-7-((dimethylamino)methyl)-22,25-dihydro-11H,21H,31H-6-oxa-1,3(3,1)-diindola-2(3,4)-pyrrolacyclononaphane-22,25-dione hydrochloride
InChi Key
NYQIEYDJYFVLPO-FERBBOLQSA-N
InChi Code
InChI=1S/C28H28N4O3.ClH/c1-30(2)15-18-11-12-31-16-21(19-7-3-5-9-23(19)31)25-26(28(34)29-27(25)33)22-17-32(13-14-35-18)24-10-6-4-8-20(22)24;/h3-10,16-18H,11-15H2,1-2H3,(H,29,33,34);1H/t18-;/m0./s1
SMILES Code
O=C1NC(C2=C1C3=CN(C4=CC=CC=C34)CC[C@@H](CN(C)C)OCCN5C=C2C6=CC=CC=C56)=O.[H]Cl
Appearance
Orange to red 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
Biological target:
Ruboxistaurin HCl is a β-specific protein kinase C inhibitor. It competitively and reversibly inhibits PKCβ1 and PKCβ2 with IC50 values of 4.7 and 5.9 nM respectively.
In vitro activity:
Ruboxistaurin is able to suppress monocyte adhesion to endothelial cells under hyperglycemic conditions even in a PKC beta-specific concentration. Reference: J Diabetes Sci Technol. 2007 Nov;1(6):929-35. https://pubmed.ncbi.nlm.nih.gov/19885168/
In vivo activity:
Ruboxistaurin can effectively alleviate anterior cruciate ligament transection-induced osteoarthritis. Ruboxistaurin inhibited osteoclast formation and resorption activity by suppressing the expressions of osteoclast-related genes and (PKCδ/MAPKs) signaling cascade. Ruboxistaurin may be a potential therapeutic agent for rescuing abnormal subchondral bone deterioration and cartilage degradation in OA and reverses the vicious cycle related to osteoarthritis. Reference: Biomed Pharmacother. 2020 Nov;131:110650. https://pubmed.ncbi.nlm.nih.gov/32882584/
Solvent mg/mL mM
Solubility
DMSO 6.7 13.21
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 505.02 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. Kunt T, Forst T, Kazda C, Harzer O, Engelbach M, Löbig M, Beyer J, Pfützner A. The beta-specific protein kinase C inhibitor ruboxistaurin (LY333531) suppresses glucose-induced adhesion of human monocytes to endothelial cells in vitro. J Diabetes Sci Technol. 2007 Nov;1(6):929-35. doi: 10.1177/193229680700100620. PMID: 19885168; PMCID: PMC2769672. 2. Bär L, Hase P, Föller M. PKC regulates the production of fibroblast growth factor 23 (FGF23). PLoS One. 2019 Mar 28;14(3):e0211309. doi: 10.1371/journal.pone.0211309. PMID: 30921339; PMCID: PMC6438472. 3. Pang C, Wen L, Lu X, Luo S, Qin H, Zhang X, Zhu B, Luo S. Ruboxistaurin maintains the bone mass of subchondral bone for blunting osteoarthritis progression by inhibition of osteoclastogenesis and bone resorption activity. Biomed Pharmacother. 2020 Nov;131:110650. doi: 10.1016/j.biopha.2020.110650. Epub 2020 Sep 1. PMID: 32882584. 4. Nonaka A, Kiryu J, Tsujikawa A, Yamashiro K, Miyamoto K, Nishiwaki H, Honda Y, Ogura Y. PKC-beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats. Invest Ophthalmol Vis Sci. 2000 Aug;41(9):2702-6. PMID: 10937586.
In vitro protocol:
1. Kunt T, Forst T, Kazda C, Harzer O, Engelbach M, Löbig M, Beyer J, Pfützner A. The beta-specific protein kinase C inhibitor ruboxistaurin (LY333531) suppresses glucose-induced adhesion of human monocytes to endothelial cells in vitro. J Diabetes Sci Technol. 2007 Nov;1(6):929-35. doi: 10.1177/193229680700100620. PMID: 19885168; PMCID: PMC2769672. 2. Bär L, Hase P, Föller M. PKC regulates the production of fibroblast growth factor 23 (FGF23). PLoS One. 2019 Mar 28;14(3):e0211309. doi: 10.1371/journal.pone.0211309. PMID: 30921339; PMCID: PMC6438472.
In vivo protocol:
1. Pang C, Wen L, Lu X, Luo S, Qin H, Zhang X, Zhu B, Luo S. Ruboxistaurin maintains the bone mass of subchondral bone for blunting osteoarthritis progression by inhibition of osteoclastogenesis and bone resorption activity. Biomed Pharmacother. 2020 Nov;131:110650. doi: 10.1016/j.biopha.2020.110650. Epub 2020 Sep 1. PMID: 32882584. 2. Nonaka A, Kiryu J, Tsujikawa A, Yamashiro K, Miyamoto K, Nishiwaki H, Honda Y, Ogura Y. PKC-beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal microcirculation of diabetic rats. Invest Ophthalmol Vis Sci. 2000 Aug;41(9):2702-6. PMID: 10937586.
1: Pang C, Wen L, Lu X, Luo S, Qin H, Zhang X, Zhu B, Luo S. Ruboxistaurin maintains the bone mass of subchondral bone for blunting osteoarthritis progression by inhibition of osteoclastogenesis and bone resorption activity. Biomed Pharmacother. 2020 Sep 1;131:110650. doi: 10.1016/j.biopha.2020.110650. Epub ahead of print. PMID: 32882584. 2: Zestos AG, Carpenter C, Kim Y, Low MJ, Kennedy RT, Gnegy ME. Ruboxistaurin Reduces Cocaine-Stimulated Increases in Extracellular Dopamine by Modifying Dopamine-Autoreceptor Activity. ACS Chem Neurosci. 2019 Apr 17;10(4):1960-1969. doi: 10.1021/acschemneuro.8b00259. Epub 2018 Nov 8. PMID: 30384585; PMCID: PMC6470047. 3: Lewin AH, Brieaddy L, Deschamps JR, Imler GH, Mascarella SW, Reddy PA, Carroll FI. Synthesis and Characterization of the Selective, Reversible PKCβ Inhibitor (9 S)-9-[(Dimethylamino)methyl]-6,7,10,11-tetrahydro-9 H,18 H-5,21:12,17-dimethenodibenzo[ e,k]pyrrolo[3,4- h][1,4,13]oxadiazacyclohexadecine-18,20(19 H)-dione, Ruboxistaurin (LY333531). ACS Chem Neurosci. 2019 Jan 16;10(1):246-251. doi: 10.1021/acschemneuro.8b00196. Epub 2018 Sep 11. PMID: 30156829. 4: Sharp TE 3rd, Kubo H, Berretta RM, Starosta T, Wallner M, Schena GJ, Hobby AR, Yu D, Trappanese DM, George JC, Molkentin JD, Houser SR. Protein Kinase C Inhibition With Ruboxistaurin Increases Contractility and Reduces Heart Size in a Swine Model of Heart Failure With Reduced Ejection Fraction. JACC Basic Transl Sci. 2017 Dec 25;2(6):669-683. doi: 10.1016/j.jacbts.2017.06.007. PMID: 30062182; PMCID: PMC6058945. 5: Al-Onazi AS, Al-Rasheed NM, Attia HA, Al-Rasheed NM, Ahmed RM, Al-Amin MA, Poizat C. Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-β1/Smad and GRAP pathways. J Pharm Pharmacol. 2016 Feb;68(2):219-32. doi: 10.1111/jphp.12504. Epub 2016 Jan 28. PMID: 26817709. 6: Deissler HL, Lang GE. The Protein Kinase C Inhibitor: Ruboxistaurin. Dev Ophthalmol. 2016;55:295-301. doi: 10.1159/000431204. Epub 2015 Oct 26. PMID: 26501476. 7: Tuttle KR, McGill JB, Bastyr EJ 3rd, Poi KK, Shahri N, Anderson PW. Effect of ruboxistaurin on albuminuria and estimated GFR in people with diabetic peripheral neuropathy: results from a randomized trial. Am J Kidney Dis. 2015 Apr;65(4):634-6. doi: 10.1053/j.ajkd.2014.11.024. Epub 2015 Jan 22. PMID: 25618186. 8: Bansal D, Badhan Y, Gudala K, Schifano F. Ruboxistaurin for the treatment of diabetic peripheral neuropathy: a systematic review of randomized clinical trials. Diabetes Metab J. 2013 Oct;37(5):375-84. doi: 10.4093/dmj.2013.37.5.375. Epub 2013 Oct 17. PMID: 24199167; PMCID: PMC3816139. 9: Sheetz MJ, Aiello LP, Davis MD, Danis R, Bek T, Cunha-Vaz J, Shahri N, Berg PH; MBDL and MBCU Study Groups. The effect of the oral PKC β inhibitor ruboxistaurin on vision loss in two phase 3 studies. Invest Ophthalmol Vis Sci. 2013 Mar 11;54(3):1750-7. doi: 10.1167/iovs.12-11055. PMID: 23404115. 10: Ladage D, Tilemann L, Ishikawa K, Correll RN, Kawase Y, Houser SR, Molkentin JD, Hajjar RJ. Inhibition of PKCα/β with ruboxistaurin antagonizes heart failure in pigs after myocardial infarction injury. Circ Res. 2011 Dec 9;109(12):1396-400. doi: 10.1161/CIRCRESAHA.111.255687. Epub 2011 Oct 13. PMID: 21998327; PMCID: PMC3237728. 11: Liu Y, Lei S, Gao X, Mao X, Wang T, Wong GT, Vanhoutte PM, Irwin MG, Xia Z. PKCβ inhibition with ruboxistaurin reduces oxidative stress and attenuates left ventricular hypertrophy and dysfunction in rats with streptozotocin-induced diabetes. Clin Sci (Lond). 2012 Feb;122(4):161-73. doi: 10.1042/CS20110176. PMID: 21892921. 12: Aiello LP, Vignati L, Sheetz MJ, Zhi X, Girach A, Davis MD, Wolka AM, Shahri N, Milton RC; PKC-DRS and PKC-DRS2 Study Groups. Oral protein kinase c β inhibition using ruboxistaurin: efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with diabetic retinopathy in the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study and the Protein Kinase C β Inhibitor- Diabetic Retinopathy Study 2. Retina. 2011 Nov;31(10):2084-94. doi: 10.1097/IAE.0b013e3182111669. PMID: 21862954. 13: Boyd A, Casselini C, Vinik E, Vinik A. Quality of life and objective measures of diabetic neuropathy in a prospective placebo-controlled trial of ruboxistaurin and topiramate. J Diabetes Sci Technol. 2011 May 1;5(3):714-22. doi: 10.1177/193229681100500326. PMID: 21722587; PMCID: PMC3192638. 14: Sheetz MJ, Aiello LP, Shahri N, Davis MD, Kles KA, Danis RP; Mbdv Study Group. Effect of ruboxistaurin (RBX) On visual acuity decline over a 6-year period with cessation and reinstitution of therapy: results of an open-label extension of the Protein Kinase C Diabetic Retinopathy Study 2 (PKC-DRS2). Retina. 2011 Jun;31(6):1053-9. doi: 10.1097/IAE.0b013e3181fe545f. PMID: 21386766. 15: Sahu AK, Majji AB. Effect of ruboxistaurin on the visual acuity decline associated with long-standing diabetic macular edema. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6890; author reply 6890-1. doi: 10.1167/iovs.09-4106. PMID: 21123772. 16: Danis RP, Sheetz MJ. Ruboxistaurin: PKC-beta inhibition for complications of diabetes. Expert Opin Pharmacother. 2009 Dec;10(17):2913-25. doi: 10.1517/14656560903401620. PMID: 19929710. 17: Nakamura S, Chikaraishi Y, Tsuruma K, Shimazawa M, Hara H. Ruboxistaurin, a PKCbeta inhibitor, inhibits retinal neovascularization via suppression of phosphorylation of ERK1/2 and Akt. Exp Eye Res. 2010 Jan;90(1):137-45. doi: 10.1016/j.exer.2009.09.022. Epub 2009 Oct 13. PMID: 19825373. 18: Connelly KA, Kelly DJ, Zhang Y, Prior DL, Advani A, Cox AJ, Thai K, Krum H, Gilbert RE. Inhibition of protein kinase C-beta by ruboxistaurin preserves cardiac function and reduces extracellular matrix production in diabetic cardiomyopathy. Circ Heart Fail. 2009 Mar;2(2):129-37. doi: 10.1161/CIRCHEARTFAILURE.108.765750. Epub 2009 Feb 10. PMID: 19808328. 19: Liu Q, Chen X, Macdonnell SM, Kranias EG, Lorenz JN, Leitges M, Houser SR, Molkentin JD. Protein kinase C{alpha}, but not PKC{beta} or PKC{gamma}, regulates contractility and heart failure susceptibility: implications for ruboxistaurin as a novel therapeutic approach. Circ Res. 2009 Jul 17;105(2):194-200. doi: 10.1161/CIRCRESAHA.109.195313. Epub 2009 Jun 25. PMID: 19556521; PMCID: PMC2749656. 20: Schwartz SG, Flynn HW Jr, Aiello LP. Ruboxistaurin mesilate hydrate for diabetic retinopathy. Drugs Today (Barc). 2009 Apr;45(4):269-74. doi: 10.1358/dot.2009.45.4.1354195. PMID: 19499092.