SCR7 pyrazine | CAS#14892-97-8 | NHEJ inhibitor

MedKoo Cat#: 563572 | Name: SCR7 pyrazine

Description:

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

SCR7 pyrazine is an inhibitor of nonhomologous end-joining (NHEJ), enhancing CRISPR-Cas9-mediated homology-directed repair (HDR) in vitro.

Chemical Structure

SCR7 pyrazine

CAS#14892-97-8

Theoretical Analysis

MedKoo Cat#: 563572

Name: SCR7 pyrazine

CAS#: 14892-97-8

Chemical Formula: C18H12N4OS

Exact Mass: 332.0700

Molecular Weight: 332.38

Elemental Analysis: C, 65.05; H, 3.64; N, 16.86; O, 4.81; S, 9.65

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 6,150.00	2 Weeks

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Synonym

SCR7 pyrazine; SCR-7 pyrazine; SCR 7 pyrazine;

IUPAC/Chemical Name

2,3-Dihydro-6,7-diphenyl-2-thioxo-4(1H)-pteridinone

InChi Key

GSRTWXVBHGOUBU-UHFFFAOYSA-N

InChi Code

InChI=1S/C18H12N4OS/c23-17-15-16(21-18(24)22-17)20-14(12-9-5-2-6-10-12)13(19-15)11-7-3-1-4-8-11/h1-10H,(H2,20,21,22,23,24)

SMILES Code

O=C1NC(NC2=NC(C3=CC=CC=C3)=C(C4=CC=CC=C4)N=C12)=S

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

2933598000

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

SCR7 is a specific DNA Ligase IV inhibitor, which blocks nonhomologous end-joining (NHEJ).

In vitro activity:

NHEJ inhibitors could be used in conjunction with standard therapy (etoposide and cisplatin) for colon cancer treatments. In a LoVo human colorectal adenocarcinoma cell line, the combination of SCR7 and NU7441 synergistically increased the cytotoxicity of cisplatin and etoposide, but the effect of SCR7 was more pronounced. SCR7 and NU7441 also significantly increased etoposide. Reference: Mol Biol Rep. 2021 Jan;48(1):709-720. https://pubmed.ncbi.nlm.nih.gov/33389482/

In vivo activity:

SCR7 was found to be effective in increasing oligonucleotide-based knock-in improved genome-editing via oviductal nucleic acids (i-GONAD) delivery in rats. These findings will help advance in situ genome editing. Reference: BMC Biotechnol. 2021 Nov 1;21(1):63. https://pubmed.ncbi.nlm.nih.gov/34724929/

	Solvent	mg/mL	mM
Solubility
	DMSO	33.4	100.00
	Ethanol	6.7	20.00

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 332.38 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. Kopa P, Macieja A, Pastwa E, Majsterek I, Poplawski T. DNA double-strand breaks repair inhibitors potentiates the combined effect of VP-16 and CDDP in human colorectal adenocarcinoma (LoVo) cells. Mol Biol Rep. 2021 Jan;48(1):709-720. doi: 10.1007/s11033-020-06124-9. Epub 2021 Jan 2. PMID: 33389482. 2. Vartak SV, Swarup HA, Gopalakrishnan V, Gopinatha VK, Ropars V, Nambiar M, John F, Kothanahally SKS, Kumari R, Kumari N, Ray U, Radha G, Dinesh D, Pandey M, Ananda H, Karki SS, Srivastava M, Charbonnier JB, Choudhary B, Mantelingu K, Raghavan SC. Autocyclized and oxidized forms of SCR7 induce cancer cell death by inhibiting nonhomologous DNA end joining in a Ligase IV dependent manner. FEBS J. 2018 Nov;285(21):3959-3976. doi: 10.1111/febs.14661. Epub 2018 Oct 8. PMID: 30230716. 3. Aoshima T, Kobayashi Y, Takagi H, Iijima K, Sato M, Takabayashi S. Modification of improved-genome editing via oviductal nucleic acids delivery (i-GONAD)-mediated knock-in in rats. BMC Biotechnol. 2021 Nov 1;21(1):63. doi: 10.1186/s12896-021-00723-5. PMID: 34724929; PMCID: PMC8561937. 4. Gopalakrishnan V, Sharma S, Ray U, Manjunath M, Lakshmanan D, Vartak SV, Gopinatha VK, Srivastava M, Kempegowda M, Choudhary B, Raghavan SC. SCR7, an inhibitor of NHEJ can sensitize tumor cells to ionization radiation. Mol Carcinog. 2021 Sep;60(9):627-643. doi: 10.1002/mc.23329. Epub 2021 Jun 30. PMID: 34192388.

In vitro protocol:

In vivo protocol:

1. Aoshima T, Kobayashi Y, Takagi H, Iijima K, Sato M, Takabayashi S. Modification of improved-genome editing via oviductal nucleic acids delivery (i-GONAD)-mediated knock-in in rats. BMC Biotechnol. 2021 Nov 1;21(1):63. doi: 10.1186/s12896-021-00723-5. PMID: 34724929; PMCID: PMC8561937. 2. Gopalakrishnan V, Sharma S, Ray U, Manjunath M, Lakshmanan D, Vartak SV, Gopinatha VK, Srivastava M, Kempegowda M, Choudhary B, Raghavan SC. SCR7, an inhibitor of NHEJ can sensitize tumor cells to ionization radiation. Mol Carcinog. 2021 Sep;60(9):627-643. doi: 10.1002/mc.23329. Epub 2021 Jun 30. PMID: 34192388.

1: Gerlach M, Kraft T, Brenner B, Petersen B, Niemann H, Montag J. Efficient Knock-in of a Point Mutation in Porcine Fibroblasts Using the CRISPR/Cas9-GMNN Fusion Gene. Genes (Basel). 2018 Jun 13;9(6). pii: E296. doi: 10.3390/genes9060296. PubMed PMID: 29899280; PubMed Central PMCID: PMC6027509. 2: Geerlings MJ, Volokhina EB, de Jong EK, van de Kar N, Pauper M, Hoyng CB, van den Heuvel LP, den Hollander AI. Genotype-phenotype correlations of low-frequency variants in the complement system in renal disease and age-related macular degeneration. Clin Genet. 2018 Jun 11. doi: 10.1111/cge.13392. [Epub ahead of print] PubMed PMID: 29888403. 3: Hu Z, Shi Z, Guo X, Jiang B, Wang G, Luo D, Chen Y, Zhu YS. Ligase IV inhibitor SCR7 enhances gene editing directed by CRISPR-Cas9 and ssODN in human cancer cells. Cell Biosci. 2018 Feb 19;8:12. doi: 10.1186/s13578-018-0200-z. eCollection 2018. PubMed PMID: 29468011; PubMed Central PMCID: PMC5819182. 4: Shao S, Ren C, Liu Z, Bai Y, Chen Z, Wei Z, Wang X, Zhang Z, Xu K. Enhancing CRISPR/Cas9-mediated homology-directed repair in mammalian cells by expressing Saccharomyces cerevisiae Rad52. Int J Biochem Cell Biol. 2017 Nov;92:43-52. doi: 10.1016/j.biocel.2017.09.012. Epub 2017 Sep 18. PubMed PMID: 28928041. 5: Li G, Zhang X, Zhong C, Mo J, Quan R, Yang J, Liu D, Li Z, Yang H, Wu Z. Small molecules enhance CRISPR/Cas9-mediated homology-directed genome editing in primary cells. Sci Rep. 2017 Aug 21;7(1):8943. doi: 10.1038/s41598-017-09306-x. PubMed PMID: 28827551; PubMed Central PMCID: PMC5566437. 6: Darwish S, Parang K, Marshall J, Goebel DJ, Tiwari R. Efficient synthesis of CN2097 using in situ activation of sulfhydryl group. Tetrahedron Lett. 2017 Aug 2;58(31):3053-3056. doi: 10.1016/j.tetlet.2017.06.066. Epub 2017 Jun 23. PubMed PMID: 28824209; PubMed Central PMCID: PMC5557301. 7: Lin C, Li H, Hao M, Xiong D, Luo Y, Huang C, Yuan Q, Zhang J, Xia N. Increasing the Efficiency of CRISPR/Cas9-mediated Precise Genome Editing of HSV-1 Virus in Human Cells. Sci Rep. 2016 Oct 7;6:34531. doi: 10.1038/srep34531. PubMed PMID: 27713537; PubMed Central PMCID: PMC5054376. 8: Gkotzamanidou M, Terpos E, Bamia C, Munshi NC, Dimopoulos MA, Souliotis VL. DNA repair of myeloma plasma cells correlates with clinical outcome: the effect of the nonhomologous end-joining inhibitor SCR7. Blood. 2016 Sep 1;128(9):1214-25. doi: 10.1182/blood-2016-01-691618. Epub 2016 Jul 21. PubMed PMID: 27443291; PubMed Central PMCID: PMC5524533. 9: Greco GE, Matsumoto Y, Brooks RC, Lu Z, Lieber MR, Tomkinson AE. SCR7 is neither a selective nor a potent inhibitor of human DNA ligase IV. DNA Repair (Amst). 2016 Jul;43:18-23. doi: 10.1016/j.dnarep.2016.04.004. Epub 2016 May 7. PubMed PMID: 27235626; PubMed Central PMCID: PMC5042453. 10: Ma Y, Chen W, Zhang X, Yu L, Dong W, Pan S, Gao S, Huang X, Zhang L. Increasing the efficiency of CRISPR/Cas9-mediated precise genome editing in rats by inhibiting NHEJ and using Cas9 protein. RNA Biol. 2016 Jul 2;13(7):605-12. doi: 10.1080/15476286.2016.1185591. Epub 2016 May 10. PubMed PMID: 27163284; PubMed Central PMCID: PMC4962809. 11: Liu M, Wang Y, Wang F, Xia M, Liu Y, Chen Y, Zhao MH. Interaction of uromodulin and complement factor H enhances C3b inactivation. J Cell Mol Med. 2016 Oct;20(10):1821-8. doi: 10.1111/jcmm.12872. Epub 2016 Apr 26. PubMed PMID: 27113631; PubMed Central PMCID: PMC5020621. 12: Wang FM, Song D, Pang Y, Song Y, Yu F, Zhao MH. The dysfunctions of complement factor H in lupus nephritis. Lupus. 2016 Oct;25(12):1328-40. doi: 10.1177/0961203316642307. Epub 2016 Apr 11. PubMed PMID: 27068115. 13: Yang D, Scavuzzo MA, Chmielowiec J, Sharp R, Bajic A, Borowiak M. Enrichment of G2/M cell cycle phase in human pluripotent stem cells enhances HDR-mediated gene repair with customizable endonucleases. Sci Rep. 2016 Feb 18;6:21264. doi: 10.1038/srep21264. PubMed PMID: 26887909; PubMed Central PMCID: PMC4757933. 14: Song J, Yang D, Xu J, Zhu T, Chen YE, Zhang J. RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency. Nat Commun. 2016 Jan 28;7:10548. doi: 10.1038/ncomms10548. PubMed PMID: 26817820; PubMed Central PMCID: PMC4738357. 15: Vartak SV, Raghavan SC. Inhibition of nonhomologous end joining to increase the specificity of CRISPR/Cas9 genome editing. FEBS J. 2015 Nov;282(22):4289-94. doi: 10.1111/febs.13416. Epub 2015 Sep 9. Review. PubMed PMID: 26290158. 16: Chu VT, Weber T, Wefers B, Wurst W, Sander S, Rajewsky K, Kühn R. Increasing the efficiency of homology-directed repair for CRISPR-Cas9-induced precise gene editing in mammalian cells. Nat Biotechnol. 2015 May;33(5):543-8. doi: 10.1038/nbt.3198. Epub 2015 Mar 24. PubMed PMID: 25803306. 17: Maruyama T, Dougan SK, Truttmann MC, Bilate AM, Ingram JR, Ploegh HL. Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. Nat Biotechnol. 2015 May;33(5):538-42. doi: 10.1038/nbt.3190. Epub 2015 Mar 23. Erratum in: Nat Biotechnol. 2016 Feb;34(2):210. PubMed PMID: 25798939; PubMed Central PMCID: PMC4618510. 18: John F, George J, Srivastava M, Hassan PA, Aswal VK, Karki SS, Raghavan SC. Pluronic copolymer encapsulated SCR7 as a potential anticancer agent. Faraday Discuss. 2015;177:155-61. doi: 10.1039/c4fd00176a. PubMed PMID: 25608025. 19: John F, George J, Vartak SV, Srivastava M, Hassan PA, Aswal VK, Karki SS, Raghavan SC. Enhanced efficacy of pluronic copolymer micelle encapsulated SCR7 against cancer cell proliferation. Macromol Biosci. 2015 Apr;15(4):521-34. doi: 10.1002/mabi.201400480. Epub 2014 Dec 16. PubMed PMID: 25515310. 20: Wyatt MK, Tsai JY, Mishra S, Campos M, Jaworski C, Fariss RN, Bernstein SL, Wistow G. Interaction of complement factor h and fibulin3 in age-related macular degeneration. PLoS One. 2013 Jun 28;8(6):e68088. doi: 10.1371/journal.pone.0068088. Print 2013. PubMed PMID: 23840815; PubMed Central PMCID: PMC3696004.

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