SU-9516 | CAS#377090-84-1 | CDK inhibitor

MedKoo Cat#: 531313 | Name: SU-9516

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Description:

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

SU-9516 is a 3-substituted indolinone CDK inhibitor with IC50 of 22 nM, 40 nM, and 200 nM for CDK2, CDK1, and CDK4, respectively.

Chemical Structure

SU-9516

CAS#377090-84-1

Theoretical Analysis

MedKoo Cat#: 531313

Name: SU-9516

CAS#: 377090-84-1

Chemical Formula: C13H11N3O2

Exact Mass: 241.0851

Molecular Weight: 241.25

Elemental Analysis: C, 64.72; H, 4.60; N, 17.42; O, 13.26

Price and Availability

Size	Price	Availability
5mg	USD 300.00	2 weeks
10mg	USD 500.00	2 weeks
25mg	USD 750.00	2 weeks

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Related CAS #

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Synonym

SU-9516; SU 9516; SU9516.

IUPAC/Chemical Name

(Z)-3-((1H-imidazol-5-yl)methylene)-5-methoxyindolin-2-one

InChi Key

QNUKRWAIZMBVCU-WCIBSUBMSA-N

InChi Code

InChI=1S/C13H11N3O2/c1-18-9-2-3-12-10(5-9)11(13(17)16-12)4-8-6-14-7-15-8/h2-7H,1H3,(H,14,15)(H,16,17)/b11-4-

SMILES Code

O=C1NC2=C(C=C(OC)C=C2)/C1=C/C3=CN=CN3

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

Instruction

View handling instruction

Biological target:

SU-9516 is a potent inhibitor of several CDKs with selectivity for Cdk2 (IC50s = 22, 40, and 200 nM for Cdk2/cyclin A, Cdk1/cyclin B, and Cdk4/cyclin D1). It does not inhibit PKC, p38, PDGFR, or EGFR (IC50s = >10 µM).

In vitro activity:

This study provides a rationale for clinical use of Bcl-2 family inhibitors, such as SU-9516, in combination with CDK2 inhibitors for treatment of Mcl-1-dependent colorectal tumors associated with expression of Bcl-2, Bcl-XL and Bcl-w proteins. Caco-2 and HT29 cells that are relatively resistant to ABT-737 are also partially sensitive to SU-9516, which increased sensitivity of Caco-2 but not HT29 cells to ABT-737. Treatment of HT29 cells with SU-9516 is associated with decreased expression of p53. Reference: Gen Physiol Biophys. 2017 Dec;36(5):539-547. https://pubmed.ncbi.nlm.nih.gov/29372687/

In vivo activity:

This study demonstrates that SU-9516 has potential for the treatment of Duchenne muscular dystrophy (DMD). In a mouse model of DMD, oral administration of SU-9516 increased α7β1 integrin in skeletal muscle, ameliorated pathology, and improved muscle function. These improvements were mediated through SU-9516 inhibitory actions on the p65-NF-κB pro-inflammatory and Ste20-related proline alanine rich kinase (SPAK)/OSR1 signaling pathways. Reference: Mol Ther. 2017 Jun 7;25(6):1395-1407. https://pubmed.ncbi.nlm.nih.gov/28391962/

	Solvent	mg/mL	mM
Solubility
	DMF	5.0	20.73
	DMSO	5.0	20.73
	DMSO:PBS (pH 7.2) (1:1)	0.5	2.07

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 241.25 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. Štefaniková A, Klačanová K, Pilchová I, Hatok J, Račay P. Cyclin-dependent kinase 2 inhibitor SU9516 increases sensitivity of colorectal carcinoma cells Caco-2 but not HT29 to BH3 mimetic ABT-737. Gen Physiol Biophys. 2017 Dec;36(5):539-547. doi: 10.4149/gpb_2017030. PMID: 29372687. 2. Uchiyama H, Sowa Y, Wakada M, Yogosawa M, Nakanishi R, Horinaka M, Shimazaki C, Taniwaki M, Sakai T. Cyclin-dependent kinase inhibitor SU9516 enhances sensitivity to methotrexate in human T-cell leukemia Jurkat cells. Cancer Sci. 2010 Mar;101(3):728-34. doi: 10.1111/j.1349-7006.2009.01449.x. Epub 2009 Nov 27. PMID: 20059476. 3. Guo Q, Jin L, Zhu HY, Li XC, Zhang YC, Xing XX, Zhang GL, Xuan MF, Luo QR, Luo ZB, Wang JX, Kang JD, Yin XJ. CDK inhibitor SU9516 induces tetraploid blastocyst formation from parthenogenetically activated porcine embryos. Biotechnol Lett. 2017 Jul;39(7):951-957. doi: 10.1007/s10529-017-2321-6. Epub 2017 Mar 17. PMID: 28315059. 4. Sarathy A, Wuebbles RD, Fontelonga TM, Tarchione AR, Mathews Griner LA, Heredia DJ, Nunes AM, Duan S, Brewer PD, Van Ry T, Hennig GW, Gould TW, Dulcey AE, Wang A, Xu X, Chen CZ, Hu X, Zheng W, Southall N, Ferrer M, Marugan J, Burkin DJ. SU9516 Increases α7β1 Integrin and Ameliorates Disease Progression in the mdx Mouse Model of Duchenne Muscular Dystrophy. Mol Ther. 2017 Jun 7;25(6):1395-1407. doi: 10.1016/j.ymthe.2017.03.022. Epub 2017 Apr 5. PMID: 28391962; PMCID: PMC5474963.

In vitro protocol:

In vivo protocol:

1. Guo Q, Jin L, Zhu HY, Li XC, Zhang YC, Xing XX, Zhang GL, Xuan MF, Luo QR, Luo ZB, Wang JX, Kang JD, Yin XJ. CDK inhibitor SU9516 induces tetraploid blastocyst formation from parthenogenetically activated porcine embryos. Biotechnol Lett. 2017 Jul;39(7):951-957. doi: 10.1007/s10529-017-2321-6. Epub 2017 Mar 17. PMID: 28315059. 2. Sarathy A, Wuebbles RD, Fontelonga TM, Tarchione AR, Mathews Griner LA, Heredia DJ, Nunes AM, Duan S, Brewer PD, Van Ry T, Hennig GW, Gould TW, Dulcey AE, Wang A, Xu X, Chen CZ, Hu X, Zheng W, Southall N, Ferrer M, Marugan J, Burkin DJ. SU9516 Increases α7β1 Integrin and Ameliorates Disease Progression in the mdx Mouse Model of Duchenne Muscular Dystrophy. Mol Ther. 2017 Jun 7;25(6):1395-1407. doi: 10.1016/j.ymthe.2017.03.022. Epub 2017 Apr 5. PMID: 28391962; PMCID: PMC5474963.

1: Štefaniková A, Klačanová K, Pilchová I, Hatok J, Račay P. Cyclin-dependent kinase 2 inhibitor SU9516 increases sensitivity of colorectal carcinoma cells Caco-2 but not HT29 to BH3 mimetic ABT-737. Gen Physiol Biophys. 2017 Dec;36(5):539-547. doi: 10.4149/gpb_2017030. PMID: 29372687. 2: Sarathy A, Wuebbles RD, Fontelonga TM, Tarchione AR, Mathews Griner LA, Heredia DJ, Nunes AM, Duan S, Brewer PD, Van Ry T, Hennig GW, Gould TW, Dulcey AE, Wang A, Xu X, Chen CZ, Hu X, Zheng W, Southall N, Ferrer M, Marugan J, Burkin DJ. SU9516 Increases α7β1 Integrin and Ameliorates Disease Progression in the mdx Mouse Model of Duchenne Muscular Dystrophy. Mol Ther. 2017 Jun 7;25(6):1395-1407. doi: 10.1016/j.ymthe.2017.03.022. Epub 2017 Apr 5. PMID: 28391962; PMCID: PMC5474963. 3: Guo Q, Jin L, Zhu HY, Li XC, Zhang YC, Xing XX, Zhang GL, Xuan MF, Luo QR, Luo ZB, Wang JX, Kang JD, Yin XJ. CDK inhibitor SU9516 induces tetraploid blastocyst formation from parthenogenetically activated porcine embryos. Biotechnol Lett. 2017 Jul;39(7):951-957. doi: 10.1007/s10529-017-2321-6. Epub 2017 Mar 17. PMID: 28315059. 4: Arai K, Eguchi T, Rahman MM, Sakamoto R, Masuda N, Nakatsura T, Calderwood SK, Kozaki K, Itoh M. A Novel High-Throughput 3D Screening System for EMT Inhibitors: A Pilot Screening Discovered the EMT Inhibitory Activity of CDK2 Inhibitor SU9516. PLoS One. 2016 Sep 13;11(9):e0162394. doi: 10.1371/journal.pone.0162394. PMID: 27622654; PMCID: PMC5021355. 5: Opyrchal M, Salisbury JL, Iankov I, Goetz MP, McCubrey J, Gambino MW, Malatino L, Puccia G, Ingle JN, Galanis E, D'Assoro AB. Inhibition of Cdk2 kinase activity selectively targets the CD44⁺/CD24⁻/Low stem-like subpopulation and restores chemosensitivity of SUM149PT triple-negative breast cancer cells. Int J Oncol. 2014 Sep;45(3):1193-9. doi: 10.3892/ijo.2014.2523. Epub 2014 Jun 25. PMID: 24970653; PMCID: PMC4121417. 6: Betzi S, Alam R, Martin M, Lubbers DJ, Han H, Jakkaraj SR, Georg GI, Schönbrunn E. Discovery of a potential allosteric ligand binding site in CDK2. ACS Chem Biol. 2011 May 20;6(5):492-501. doi: 10.1021/cb100410m. Epub 2011 Feb 22. PMID: 21291269; PMCID: PMC3098941. 7: Uchiyama H, Sowa Y, Wakada M, Yogosawa M, Nakanishi R, Horinaka M, Shimazaki C, Taniwaki M, Sakai T. Cyclin-dependent kinase inhibitor SU9516 enhances sensitivity to methotrexate in human T-cell leukemia Jurkat cells. Cancer Sci. 2010 Mar;101(3):728-34. doi: 10.1111/j.1349-7006.2009.01449.x. Epub 2009 Nov 27. PMID: 20059476; PMCID: PMC11158204. 8: Xiong X, Zhang Y, Gao X, Dong Z, Li L, Ji C, Fu L, Luo X, Liu H, Mei C. B5, a novel pyrrole-substituted indolinone, exerts potent antitumor efficacy through G2/M cell cycle arrest. Invest New Drugs. 2010 Feb;28(1):26-34. doi: 10.1007/s10637-008-9211-7. Epub 2009 Jan 13. PMID: 19139818. 9: Takagi K, Sowa Y, Cevik OM, Nakanishi R, Sakai T. CDK inhibitor enhances the sensitivity to 5-fluorouracil in colorectal cancer cells. Int J Oncol. 2008 May;32(5):1105-10. PMID: 18425338. 10: Heady L, Fernandez-Serra M, Mancera RL, Joyce S, Venkitaraman AR, Artacho E, Skylaris CK, Ciacchi LC, Payne MC. Novel structural features of CDK inhibition revealed by an ab initio computational method combined with dynamic simulations. J Med Chem. 2006 Aug 24;49(17):5141-53. doi: 10.1021/jm060190+. PMID: 16913703. 11: Gao N, Kramer L, Rahmani M, Dent P, Grant S. The three-substituted indolinone cyclin-dependent kinase 2 inhibitor 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516) kills human leukemia cells via down-regulation of Mcl-1 through a transcriptional mechanism. Mol Pharmacol. 2006 Aug;70(2):645-55. doi: 10.1124/mol.106.024505. Epub 2006 May 3. PMID: 16672643. 12: Collins I, Garrett MD. Targeting the cell division cycle in cancer: CDK and cell cycle checkpoint kinase inhibitors. Curr Opin Pharmacol. 2005 Aug;5(4):366-73. doi: 10.1016/j.coph.2005.04.009. PMID: 15964238. 13: Tsonis PA, Madhavan M, Call MK, Gainer S, Rice A, Del Rio-Tsonis K. Effects of a CDK inhibitor on lens regeneration. Wound Repair Regen. 2004 Jan- Feb;12(1):24-9. doi: 10.1111/j.1067-1927.2004.012107.x. PMID: 14974961. 14: Moshinsky DJ, Bellamacina CR, Boisvert DC, Huang P, Hui T, Jancarik J, Kim SH, Rice AG. SU9516: biochemical analysis of cdk inhibition and crystal structure in complex with cdk2. Biochem Biophys Res Commun. 2003 Oct 24;310(3):1026-31. doi: 10.1016/j.bbrc.2003.09.114. PMID: 14550307. 15: Yu B, Lane ME, Wadler S. SU9516, a cyclin-dependent kinase 2 inhibitor, promotes accumulation of high molecular weight E2F complexes in human colon carcinoma cells. Biochem Pharmacol. 2002 Oct 1;64(7):1091-100. doi: 10.1016/s0006-2952(02)01264-9. PMID: 12234612. 16: Lane ME, Yu B, Rice A, Lipson KE, Liang C, Sun L, Tang C, McMahon G, Pestell RG, Wadler S. A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells. Cancer Res. 2001 Aug 15;61(16):6170-7. PMID: 11507069.