RKI-1447 | CAS#1342278-01-6 | ROCK inhibitior

MedKoo Cat#: 406428 | Name: RKI-1447

Description:

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

RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer. RKI-1447 is a Type I kinase inhibitor that binds the ATP binding site through interactions with the hinge region and the DFG motif. RKI-1447 suppressed phosphorylation of the ROCK substrates MLC-2 and MYPT-1 in human cancer cells.

Chemical Structure

RKI-1447

CAS#1342278-01-6

Theoretical Analysis

MedKoo Cat#: 406428

Name: RKI-1447

CAS#: 1342278-01-6

Chemical Formula: C16H14N4O2S

Exact Mass: 326.0838

Molecular Weight: 326.37

Elemental Analysis: C, 58.88; H, 4.32; N, 17.17; O, 9.80; S, 9.82

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,650.00	2 Weeks
2g	USD 6,450.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

RKI-1447; RKI1447; RKI 1447. ROCK Inhibitor XIII.

IUPAC/Chemical Name

1-(3-Hydroxybenzyl)-3-(4-(pyridin-4-yl)thiazol-2-yl)urea

InChi Key

GDVRVPIXWXOKQO-UHFFFAOYSA-N

InChi Code

InChI=1S/C16H14N4O2S/c21-13-3-1-2-11(8-13)9-18-15(22)20-16-19-14(10-23-16)12-4-6-17-7-5-12/h1-8,10,21H,9H2,(H2,18,19,20,22)

SMILES Code

O=C(NC1=NC(C2=CC=NC=C2)=CS1)NCC3=CC=CC(O)=C3

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

Instruction

View handling instruction

Biological target:

RKI-1447 is a potent inhibitor of ROCK1 and ROCK2, with IC50 of 14.5 nM and 6.2 nM, respectively.

In vitro activity:

This study demonstrated that inhibition of ROCK signaling pathway by RKI-1447 could suppress colorectal carcinoma cell growth via cytoskeleton associated mitochondrial dysfunction and cellular bioenergetics disruption. These data suggest that RKI-1447 may be a drug candidate for the treatment of colorectal carcinoma cells. Reference: J Cell Physiol. 2020 Jan;235(1):254-266. https://pubmed.ncbi.nlm.nih.gov/31237697/

In vivo activity:

In a mouse model of nonalcoholic fatty liver disease, RKI-1447 inhibited ROCK and modulated insulin resistance, oxidative stress, and inflammation through the ROCK/TLR4/TBK1/IRF3 pathway. Reference: Med Sci Monit. 2020 Feb 6;26:e919220. https://pubmed.ncbi.nlm.nih.gov/32026851/

	Solvent	mg/mL	mM
Solubility
	DMSO	65.0	199.16

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 326.37 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

Formulation protocol:

1. Li L, Chen Q, Yu Y, Chen H, Lu M, Huang Y, Li P, Chang H. RKI-1447 suppresses colorectal carcinoma cell growth via disrupting cellular bioenergetics and mitochondrial dynamics. J Cell Physiol. 2020 Jan;235(1):254-266. doi: 10.1002/jcp.28965. Epub 2019 Jun 25. PMID: 31237697. 2. Wang J, Jiang W. The Effects of RKI-1447 in a Mouse Model of Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet and in HepG2 Human Hepatocellular Carcinoma Cells Treated with Oleic Acid. Med Sci Monit. 2020 Feb 6;26:e919220. doi: 10.12659/MSM.919220. PMID: 32026851; PMCID: PMC7020744. 3. Patel RA, Forinash KD, Pireddu R, Sun Y, Sun N, Martin MP, Schönbrunn E, Lawrence NJ, Sebti SM. RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer. Cancer Res. 2012 Oct 1;72(19):5025-34. doi: 10.1158/0008-5472.CAN-12-0954. Epub 2012 Jul 30. PMID: 22846914; PMCID: PMC3463757.

In vitro protocol:

In vivo protocol:

1. Wang J, Jiang W. The Effects of RKI-1447 in a Mouse Model of Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet and in HepG2 Human Hepatocellular Carcinoma Cells Treated with Oleic Acid. Med Sci Monit. 2020 Feb 6;26:e919220. doi: 10.12659/MSM.919220. PMID: 32026851; PMCID: PMC7020744. 2. Patel RA, Forinash KD, Pireddu R, Sun Y, Sun N, Martin MP, Schönbrunn E, Lawrence NJ, Sebti SM. RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer. Cancer Res. 2012 Oct 1;72(19):5025-34. doi: 10.1158/0008-5472.CAN-12-0954. Epub 2012 Jul 30. PMID: 22846914; PMCID: PMC3463757.

1: Pepich A, Tümmler C, Abu Ajamieh S, Treis D, Boje AS, Vellema Q, Tsea I, Åkerlund E, Seashore-Ludlow B, Shirazi Fard S, Kogner P, Johnsen JI, Wickström M. The ROCK-1/2 inhibitor RKI-1447 blocks N-MYC, promotes cell death, and emerges as a synergistic partner for BET inhibitors in neuroblastoma. Cancer Lett. 2024 Sep 20:217261. doi: 10.1016/j.canlet.2024.217261. Epub ahead of print. PMID: 39307412. 2: Su M, Fleischer T, Grosheva I, Horev MB, Olszewska M, Mattioli CC, Barr H, Plotnikov A, Carvalho S, Moskovich Y, Minden MD, Chapal-Ilani N, Wainstein A, Papapetrou EP, Dezorella N, Cheng T, Kaushansky N, Geiger B, Shlush LI. Targeting SRSF2 mutations in leukemia with RKI-1447: A strategy to impair cellular division and nuclear structure. iScience. 2024 Mar 6;27(4):109443. doi: 10.1016/j.isci.2024.109443. PMID: 38558935; PMCID: PMC10981050. 3: Djokovic N, Djuric A, Ruzic D, Srdic-Rajic T, Nikolic K. Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma. Pharmaceuticals (Basel). 2023 Feb 14;16(2):294. doi: 10.3390/ph16020294. PMID: 37259439; PMCID: PMC9964546. 4: Li H, Wang C, Jin Y, Cai Y, Sun H, Liu M. The integrative analysis of competitive endogenous RNA regulatory networks in osteoporosis. Sci Rep. 2022 Jun 9;12(1):9549. doi: 10.1038/s41598-022-13791-0. PMID: 35680981; PMCID: PMC9184474. 5: Ning L, Gao L, Zhang F, Li X, Wang T. Mechanical Stretch Induces Annulus Fibrosus Cell Senescence through Activation of the RhoA/ROCK Pathway. Biomed Res Int. 2021 Nov 19;2021:5321121. doi: 10.1155/2021/5321121. PMID: 34840974; PMCID: PMC8626192. 6: Jing H, Chen P, Hui T, Yu Z, Zhou J, Fei E, Wang S, Ren D, Lai X, Li B. Synapse-specific Lrp4 mRNA enrichment requires Lrp4/MuSK signaling, muscle activity and Wnt non-canonical pathway. Cell Biosci. 2021 Jun 5;11(1):105. doi: 10.1186/s13578-021-00619-z. PMID: 34090516; PMCID: PMC8180081. 7: de Sousa GR, Vieira GM, das Chagas PF, Pezuk JA, Brassesco MS. Should we keep rocking? Portraits from targeting Rho kinases in cancer. Pharmacol Res. 2020 Oct;160:105093. doi: 10.1016/j.phrs.2020.105093. Epub 2020 Jul 26. PMID: 32726671. 8: Wang J, Jiang W. The Effects of RKI-1447 in a Mouse Model of Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet and in HepG2 Human Hepatocellular Carcinoma Cells Treated with Oleic Acid. Med Sci Monit. 2020 Feb 6;26:e919220. doi: 10.12659/MSM.919220. PMID: 32026851; PMCID: PMC7020744. 9: Dyberg C, Andonova T, Olsen TK, Brodin B, Kool M, Kogner P, Johnsen JI, Wickström M. Inhibition of Rho-Associated Kinase Suppresses Medulloblastoma Growth. Cancers (Basel). 2019 Dec 26;12(1):73. doi: 10.3390/cancers12010073. PMID: 31888022; PMCID: PMC7016943. 10: Cornet C, Dyballa S, Terriente J, Di Giacomo V. ZeOncoTest: Refining and Automating the Zebrafish Xenograft Model for Drug Discovery in Cancer. Pharmaceuticals (Basel). 2019 Dec 24;13(1):1. doi: 10.3390/ph13010001. PMID: 31878274; PMCID: PMC7169390. 11: Guan Z, Baty JJ, Zhang S, Remedies CE, Inscho EW. Rho kinase inhibitors reduce voltage-dependent Ca2+ channel signaling in aortic and renal microvascular smooth muscle cells. Am J Physiol Renal Physiol. 2019 Nov 1;317(5):F1132-F1141. doi: 10.1152/ajprenal.00212.2018. Epub 2019 Aug 21. PMID: 31432708; PMCID: PMC6879933. 12: Li L, Chen Q, Yu Y, Chen H, Lu M, Huang Y, Li P, Chang H. RKI-1447 suppresses colorectal carcinoma cell growth via disrupting cellular bioenergetics and mitochondrial dynamics. J Cell Physiol. 2020 Jan;235(1):254-266. doi: 10.1002/jcp.28965. Epub 2019 Jun 25. PMID: 31237697. 13: Dang Y, Wang C, Shah P, Waxman S, Loewen RT, Loewen NA. RKI-1447, a Rho kinase inhibitor, causes ocular hypotension, actin stress fiber disruption, and increased phagocytosis. Graefes Arch Clin Exp Ophthalmol. 2019 Jan;257(1):101-109. doi: 10.1007/s00417-018-4175-6. Epub 2018 Nov 19. PMID: 30456419; PMCID: PMC7818579. 14: Tornin J, Hermida-Prado F, Padda RS, Gonzalez MV, Alvarez-Fernandez C, Rey V, Martinez-Cruzado L, Estupiñan O, Menendez ST, Fernandez-Nevado L, Astudillo A, Rodrigo JP, Lucien F, Kim Y, Leong HS, Garcia-Pedrero JM, Rodriguez R. FUS- CHOP Promotes Invasion in Myxoid Liposarcoma through a SRC/FAK/RHO/ROCK- Dependent Pathway. Neoplasia. 2018 Jan;20(1):44-56. doi: 10.1016/j.neo.2017.11.004. Epub 2017 Nov 28. PMID: 29190494; PMCID: PMC5747526. 15: Thompson JM, Nguyen QH, Singh M, Pavesic MW, Nesterenko I, Nelson LJ, Liao AC, Razorenova OV. Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma. Oncogene. 2017 Feb 23;36(8):1080-1089. doi: 10.1038/onc.2016.272. Epub 2016 Nov 14. PMID: 27841867; PMCID: PMC5323317. 16: Patel RA, Forinash KD, Pireddu R, Sun Y, Sun N, Martin MP, Schönbrunn E, Lawrence NJ, Sebti SM. RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer. Cancer Res. 2012 Oct 1;72(19):5025-34. doi: 10.1158/0008-5472.CAN-12-0954. Epub 2012 Jul 30. PMID: 22846914; PMCID: PMC3463757.