Netarsudil Mesylate

We are open as normal during COVID-19 pandemic. Order online, same day shipping out from North Carolina, USA

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

MedKoo CAT#: 525747

CAS#: 1422144-42-0 (mesylate)

Description: 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.


Price and Availability

Size Price Shipping out time Quantity
Inquire bulk and customized quantity

Pricing updated 2020-10-31. Prices are subject to change without notice.

Netarsudil Mesylate is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote


Chemical Structure

img

Theoretical Analysis

MedKoo Cat#: 525747
Name: Netarsudil Mesylate
CAS#: 1422144-42-0 (mesylate)
Chemical Formula: C30H35N3O9S2
Exact Mass: 645.18147
Molecular Weight: 645.742
Elemental Analysis: C, 55.80; H, 5.46; N, 6.51; O, 22.30; S, 9.93


Related CAS #: 1422144-42-0 (mesylate)   1254032-66-0 (free base)   1253952-02-1 (HCl)    

Synonym: AR-13324; AR13324; AR 13324; Netarsudil Mesylate; Rhopressa;

IUPAC/Chemical Name: (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dimethanesulfonate

InChi Key: QQDRLKRHJOAQDC-FBHGDYMESA-N

InChi Code: InChI=1S/C28H27N3O3.2CH4O3S/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;2*1-5(2,3)4/h3-14,16,26H,15,17,29H2,1-2H3,(H,31,32);2*1H3,(H,2,3,4)/t26-;;/m1../s1

SMILES Code: CS(=O)(O)=O.CS(=O)(O)=O.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


Technical Data

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


Additional Information

Rho-associated protein kinase (ROCK) is a kinase belonging to the AGC (PKA/ PKG/PKC) family of serine-threonine kinases. It is involved mainly in regulating the shape and movement of cells by acting on the cytoskeleton. ROCK signaling plays an important role in many diseases including diabetes, neurodegenerative diseases such as Parkinson´s disease and amyotrophic lateral sclerosis, pulmonary hypertension and cancer. It has been shown to be involved in causing tissue thickening and stiffening around tumours in a mouse model of skin cancer, principally by increasing the amount of collagen in the tissue around the tumour.


References

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.