Netarsudil free base | CAS#1254032-66-0 |

MedKoo Cat#: 573248 | Name: Netarsudil free base

Description:

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

Netarsudil, also known as AR-11324, is a Rho-associated protein kinase inhibitor. Netarsudil is potential useful for treating glaucoma and/or reducing intraocular pressure. Netarsudil Increases Outflow Facility in Human Eyes Through Multiple Mechanisms. Netarsudil inhibited kinases ROCK1 and ROCK2 with a Ki of 1 nM each, disrupted actin stress fibers and focal adhesions in TM cells with IC50s of 79 and 16 nM, respectively, and blocked the profibrotic effects of TGF-β2 in HTM cells. Netarsudil produced large reductions in IOP in rabbits and monkeys that were sustained for at least 24 h after once daily dosing, with transient, mild hyperemia observed as the only adverse effect.

Chemical Structure

Netarsudil free base

CAS#1254032-66-0 (free base)

Theoretical Analysis

MedKoo Cat#: 573248

Name: Netarsudil free base

CAS#: 1254032-66-0 (free base)

Chemical Formula: C28H27N3O3

Exact Mass: 453.2052

Molecular Weight: 453.54

Elemental Analysis: C, 74.15; H, 6.00; N, 9.27; O, 10.58

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.

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Related CAS #

1422144-42-0 (mesylate) 1254032-66-0 (free base) 1253952-02-1 (HCl)

Synonym

AR-13324; AR13324; AR 13324; Netarsudil free base

IUPAC/Chemical Name

Benzoic acid, 2,4-dimethyl-, (4-((1S)-1-(aminomethyl)-2-(6-isoquinolinylamino)-2-oxoethyl)phenyl)methyl ester

InChi Key

OURRXQUGYQRVML-AREMUKBSSA-N

InChi Code

InChI=1S/C28H27N3O3/c1-18-3-10-25(19(2)13-18)28(33)34-17-20-4-6-21(7-5-20)26(15-29)27(32)31-24-9-8-23-16-30-12-11-22(23)14-24/h3-14,16,26H,15,17,29H2,1-2H3,(H,31,32)/t26-/m1/s1

SMILES Code

O=C(OCC1=CC=C([C@@H](CN)C(NC2=CC3=C(C=NC=C3)C=C2)=O)C=C1)C4=CC=C(C)C=C4C

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

>3 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

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 453.54 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.

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

1: Ploysangam P, Patel SP. A Case Report Illustrating the Postoperative Course of Descemetorhexis without Endothelial Keratoplasty with Topical Netarsudil Therapy. Case Rep Ophthalmol Med. 2019 Oct 13;2019:6139026. doi: 10.1155/2019/6139026. eCollection 2019. PubMed PMID: 31737390; PubMed Central PMCID: PMC6815562. 2: Mehran NA, Sinha S, Razeghinejad R. New glaucoma medications: latanoprostene bunod, netarsudil, and fixed combination netarsudil-latanoprost. Eye (Lond). 2019 Nov 6. doi: 10.1038/s41433-019-0671-0. [Epub ahead of print] Review. PubMed PMID: 31695162. 3: Sinha S, Lee D, Kolomeyer NN, Myers JS, Razeghinejad R. Fixed combination netarsudil-latanoprost for the treatment of glaucoma and ocular hypertension. Expert Opin Pharmacother. 2019 Oct 30:1-7. doi: 10.1080/14656566.2019.1685499. [Epub ahead of print] PubMed PMID: 31663782. 4: Radell JE, Serle JB. Netarsudil/latanoprost fixed-dose combination for the treatment of open-angle glaucoma or ocular hypertension. Drugs Today (Barc). 2019 Sep;55(9):563-574. doi: 10.1358/dot.2019.55.9.3039670. PubMed PMID: 31584573. 5: Asrani S, Robin AL, Serle JB, Lewis RA, Usner DW, Kopczynski CC, Heah T; MERCURY-1 Study Group. Netarsudil/Latanoprost Fixed-Dose Combination for Elevated Intraocular Pressure: Three-Month Data from a Randomized Phase 3 Trial. Am J Ophthalmol. 2019 Nov;207:248-257. doi: 10.1016/j.ajo.2019.06.016. Epub 2019 Jun 21. PubMed PMID: 31229466. 6: Khouri AS, Serle JB, Bacharach J, Usner DW, Lewis RA, Braswell P, Kopczynski CC, Heah T; Rocket-4 Study Group. Once-Daily Netarsudil Versus Twice-Daily Timolol in Patients With Elevated Intraocular Pressure: The Randomized Phase 3 ROCKET-4 Study. Am J Ophthalmol. 2019 Aug;204:97-104. doi: 10.1016/j.ajo.2019.03.002. Epub 2019 Mar 9. PubMed PMID: 30862500. 7: Kahook MY, Serle JB, Mah FS, Kim T, Raizman MB, Heah T, Ramirez-Davis N, Kopczynski CC, Usner DW, Novack GD; ROCKET-2 Study Group. Long-term Safety and Ocular Hypotensive Efficacy Evaluation of Netarsudil Ophthalmic Solution: Rho Kinase Elevated IOP Treatment Trial (ROCKET-2). Am J Ophthalmol. 2019 Apr;200:130-137. doi: 10.1016/j.ajo.2019.01.003. Epub 2019 Jan 15. PubMed PMID: 30653957. 8: Dasso L, Al-Khaled T, Sonty S, Aref AA. Profile of netarsudil ophthalmic solution and its potential in the treatment of open-angle glaucoma: evidence to date. Clin Ophthalmol. 2018 Oct 4;12:1939-1944. doi: 10.2147/OPTH.S154001. eCollection 2018. Review. PubMed PMID: 30323550; PubMed Central PMCID: PMC6177382. 9: Fernandez MM. Reticular Epithelial Edema in Edematous Corneas Treated with Netarsudil. Ophthalmology. 2018 Nov;125(11):1709. doi: 10.1016/j.ophtha.2018.08.004. PubMed PMID: 30318038. 10: Kopczynski CC, Heah T. Netarsudil ophthalmic solution 0.02% for the treatment of patients with open-angle glaucoma or ocular hypertension. Drugs Today (Barc). 2018 Aug;54(8):467-478. doi: 10.1358/dot.2018.54.8.2849627. Review. PubMed PMID: 30209441. 11: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK513055/ PubMed PMID: 30000985. 12: Kazemi A, McLaren JW, Kopczynski CC, Heah TG, Novack GD, Sit AJ. The Effects of Netarsudil Ophthalmic Solution on Aqueous Humor Dynamics in a Randomized Study in Humans. J Ocul Pharmacol Ther. 2018 Jun;34(5):380-386. doi: 10.1089/jop.2017.0138. Epub 2018 Feb 22. PubMed PMID: 29469601; PubMed Central PMCID: PMC5995263. 13: Hoy SM. Netarsudil Ophthalmic Solution 0.02%: First Global Approval. Drugs. 2018 Mar;78(3):389-396. doi: 10.1007/s40265-018-0877-7. Review. PubMed PMID: 29453668. 14: Serle JB, Katz LJ, McLaurin E, Heah T, Ramirez-Davis N, Usner DW, Novack GD, Kopczynski CC; ROCKET-1 and ROCKET-2 Study Groups. Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2). Am J Ophthalmol. 2018 Feb;186:116-127. doi: 10.1016/j.ajo.2017.11.019. Epub 2017 Dec 1. PubMed PMID: 29199013. 15: Lin CW, Sherman B, Moore LA, Laethem CL, Lu DW, Pattabiraman PP, Rao PV, deLong MA, Kopczynski CC. Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma. J Ocul Pharmacol Ther. 2018 Jan/Feb;34(1-2):40-51. doi: 10.1089/jop.2017.0023. Epub 2017 Jun 13. PubMed PMID: 28609185; PubMed Central PMCID: PMC5963640. 16: Ren R, Li G, Le TD, Kopczynski C, Stamer WD, Gong H. Netarsudil Increases Outflow Facility in Human Eyes Through Multiple Mechanisms. Invest Ophthalmol Vis Sci. 2016 Nov 1;57(14):6197-6209. doi: 10.1167/iovs.16-20189. PubMed PMID: 27842161; PubMed Central PMCID: PMC5114035. 17: Li G, Mukherjee D, Navarro I, Ashpole NE, Sherwood JM, Chang J, Overby DR, Yuan F, Gonzalez P, Kopczynski CC, Farsiu S, Stamer WD. Visualization of conventional outflow tissue responses to netarsudil in living mouse eyes. Eur J Pharmacol. 2016 Sep 15;787:20-31. doi: 10.1016/j.ejphar.2016.04.002. Epub 2016 Apr 13. PubMed PMID: 27085895; PubMed Central PMCID: PMC5014700. 18: Sturdivant JM, Royalty SM, Lin CW, Moore LA, Yingling JD, Laethem CL, Sherman B, Heintzelman GR, Kopczynski CC, deLong MA. Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma. Bioorg Med Chem Lett. 2016 May 15;26(10):2475-2480. doi: 10.1016/j.bmcl.2016.03.104. Epub 2016 Apr 1. PubMed PMID: 27072905.