SGC707 | CAS#1687736-54-4 | PRMT3 inhibitor

MedKoo Cat#: 407283 | Name: SGC707

Description:

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

SGC707 is a potent, selective and cell-active allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3). SGC707 is a potent PRMT3 inhibitor (IC50 =31±2 nM, KD =53±2 nM) with outstanding selectivity (selective against 31 other methyltransferases and more than 250 non-epigenetic targets). The mechanism of action studies and crystal structure of the PRMT3-SGC707 complex confirm the allosteric inhibition mode. Importantly, SGC707 engages PRMT3 and potently inhibits its methyltransferase activity in cells. It is also bioavailable and suitable for animal studies. This well-characterized chemical probe is an excellent tool to further study the role of PRMT3 in health and disease.

Chemical Structure

SGC707

CAS#1687736-54-4

Theoretical Analysis

MedKoo Cat#: 407283

Name: SGC707

CAS#: 1687736-54-4

Chemical Formula: C16H18N4O2

Exact Mass: 298.1430

Molecular Weight: 298.35

Elemental Analysis: C, 64.41; H, 6.08; N, 18.78; O, 10.73

Price and Availability

Size	Price	Availability
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 850.00	Ready to ship
500mg	USD 1,750.00	Ready to ship
1g	USD 2,850.00	Ready to ship

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Related CAS #

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Synonym

SGC707; SGC-707; SGC 707.

IUPAC/Chemical Name

N-6-isoquinolinyl-N'-[2-oxo-2-(1-pyrrolidinyl)ethyl]-urea

InChi Key

DMIDPTCQPIJYFE-UHFFFAOYSA-N

InChi Code

InChI=1S/C16H18N4O2/c21-15(20-7-1-2-8-20)11-18-16(22)19-14-4-3-13-10-17-6-5-12(13)9-14/h3-6,9-10H,1-2,7-8,11H2,(H2,18,19,22)

SMILES Code

O=C(NCC(N1CCCC1)=O)NC2=CC3=C(C=NC=C3)C=C2

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C20R07B15

QC Data

View QC data: current batch, Lot#C20R07B15

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SGC707 is a first-in-class PRMT3 chemical probe which is a potent, selective, and cell-active allosteric inhibitor of PRMT3 with IC50 of 31 nM.

In vitro activity:

SGC707 effectively inhibits PRMT3 methyltransferase activity in cells, exhibits bioavailability, and is suitable for animal studies, making it a valuable tool for studying the role of PRMT3 in health and disease. SGC707 demonstrated remarkable potency (IC50 = 31±2 nM) and selectivity against other methyltransferases and non-epigenetic targets. The mechanism of action involves allosteric inhibition, confirmed by crystal structure studies. Reference: Angew Chem Int Ed Engl. 2015 Apr 20; 54(17): 5166–5170. https://pubmed.ncbi.nlm.nih.gov/25728001/

In vivo activity:

PRMT3 inhibition by SGC707 in hyperlipidemic mice reduces hepatic steatosis, lowers plasma triglyceride levels, and virtually eliminates atherosclerotic lesions. SGC707-treated mice showed decreased liver triglyceride stores, lower plasma triglycerides, and increased levels of taurine-conjugated bile acids with enhanced TGR5 signaling. However, there were adverse effects such as severe pruritus and scratching-associated skin lesions, leading to early study termination. Reference: Sci Rep. 2022 Jan 10;12(1):483. https://pubmed.ncbi.nlm.nih.gov/35013582/

	Solvent	mg/mL	mM
Solubility
	DMSO	54.0	181.12
	Ethanol	32.0	107.26

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 298.35 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. Kaniskan HÜ, Szewczyk MM, Yu Z, Eram MS, Yang X, Schmidt K, Luo X, Dai M, He F, Zang I, Lin Y, Kennedy S, Li F, Dobrovetsky E, Dong A, Smil D, Min SJ, Landon M, Lin-Jones J, Huang XP, Roth BL, Schapira M, Atadja P, Barsyte-Lovejoy D, Arrowsmith CH, Brown PJ, Zhao K, Jin J, Vedadi M. A potent, selective and cell-active allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3). Angew Chem Int Ed Engl. 2015 Apr 20;54(17):5166-70. doi: 10.1002/anie.201412154. Epub 2015 Feb 27. PMID: 25728001; PMCID: PMC4400258. 2. Min Z, Xiaomeng L, Zheng L, Yangge D, Xuejiao L, Longwei L, Xiao Z, Yunsong L, Ping Z, Yongsheng Z. Asymmetrical methyltransferase PRMT3 regulates human mesenchymal stem cell osteogenesis via miR-3648. Cell Death Dis. 2019 Aug 5;10(8):581. doi: 10.1038/s41419-019-1815-7. PMID: 31378783; PMCID: PMC6680051. 3. de Jong LM, Zhang Z, den Hartog Y, Sijsenaar TJP, Martins Cardoso R, Manson ML, Hankemeier T, Lindenburg PW, Salvatori DCF, Van Eck M, Hoekstra M. PRMT3 inhibitor SGC707 reduces triglyceride levels and induces pruritus in Western-type diet-fed LDL receptor knockout mice. Sci Rep. 2022 Jan 10;12(1):483. doi: 10.1038/s41598-021-04524-w. PMID: 35013582; PMCID: PMC8748717. 4. Hoekstra M, Nahon JE, de Jong LM, Kröner MJ, de Leeuw LR, Van Eck M. Inhibition of PRMT3 activity reduces hepatic steatosis without altering atherosclerosis susceptibility in apoE knockout mice. Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1402-1409. doi: 10.1016/j.bbadis.2019.02.012. Epub 2019 Feb 15. PMID: 30776415.

In vitro protocol:

In vivo protocol:

1. de Jong LM, Zhang Z, den Hartog Y, Sijsenaar TJP, Martins Cardoso R, Manson ML, Hankemeier T, Lindenburg PW, Salvatori DCF, Van Eck M, Hoekstra M. PRMT3 inhibitor SGC707 reduces triglyceride levels and induces pruritus in Western-type diet-fed LDL receptor knockout mice. Sci Rep. 2022 Jan 10;12(1):483. doi: 10.1038/s41598-021-04524-w. PMID: 35013582; PMCID: PMC8748717. 2. Hoekstra M, Nahon JE, de Jong LM, Kröner MJ, de Leeuw LR, Van Eck M. Inhibition of PRMT3 activity reduces hepatic steatosis without altering atherosclerosis susceptibility in apoE knockout mice. Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1402-1409. doi: 10.1016/j.bbadis.2019.02.012. Epub 2019 Feb 15. PMID: 30776415.

1: Zou W, Li M, Wan S, Ma J, Lian L, Luo G, Zhou Y, Li J, Zhou B. Discovery of PRMT3 Degrader for the Treatment of Acute Leukemia. Adv Sci (Weinh). 2024 Oct;11(38):e2405963. doi: 10.1002/advs.202405963. Epub 2024 Aug 9. PMID: 39120042; PMCID: PMC11481256. 2: Xiong Z, Cao J, Xiu M, Li A, Li X, Zhang Y, Zeng Q, Hu Y, Yang Y, Wu H. Chicken PRMT3 facilitates IBDV replication. Poult Sci. 2024 Sep;103(9):103989. doi: 10.1016/j.psj.2024.103989. Epub 2024 Jun 17. PMID: 38981362; PMCID: PMC11279246. 3: Zhou G, Zhang C, Peng H, Su X, Huang Q, Zhao Z, Zhao G. PRMT3 methylates HIF-1α to enhance the vascular calcification induced by chronic kidney disease. Mol Med. 2024 Jan 10;30(1):8. doi: 10.1186/s10020-023-00759-7. PMID: 38200452; PMCID: PMC10782741. 4: Wang Y, Wang C, Guan X, Ma Y, Zhang S, Li F, Yin Y, Sun Z, Chen X, Yin H. PRMT3-Mediated Arginine Methylation of METTL14 Promotes Malignant Progression and Treatment Resistance in Endometrial Carcinoma. Adv Sci (Weinh). 2023 Dec;10(36):e2303812. doi: 10.1002/advs.202303812. Epub 2023 Nov 16. PMID: 37973560; PMCID: PMC10754120. 5: Zhu J, Li X, Cai X, Zhou Z, Liao Q, Liu X, Wang J, Xiao W. Asymmetric arginine dimethylation of cytosolic RNA and DNA sensors by PRMT3 attenuates antiviral innate immunity. Proc Natl Acad Sci U S A. 2023 Sep 5;120(36):e2214956120. doi: 10.1073/pnas.2214956120. Epub 2023 Aug 28. PMID: 37639603; PMCID: PMC10483634. 6: Liao Y, Luo Z, Lin Y, Chen H, Chen T, Xu L, Orgurek S, Berry K, Dzieciatkowska M, Reisz JA, D'Alessandro A, Zhou W, Lu QR. PRMT3 drives glioblastoma progression by enhancing HIF1A and glycolytic metabolism. Cell Death Dis. 2022 Nov 9;13(11):943. doi: 10.1038/s41419-022-05389-1. PMID: 36351894; PMCID: PMC9646854. 7: Lei Y, Han P, Chen Y, Wang H, Wang S, Wang M, Liu J, Yan W, Tian D, Liu M. Protein arginine methyltransferase 3 promotes glycolysis and hepatocellular carcinoma growth by enhancing arginine methylation of lactate dehydrogenase A. Clin Transl Med. 2022 Jan;12(1):e686. doi: 10.1002/ctm2.686. PMID: 35090076; PMCID: PMC8797063. 8: de Jong LM, Zhang Z, den Hartog Y, Sijsenaar TJP, Martins Cardoso R, Manson ML, Hankemeier T, Lindenburg PW, Salvatori DCF, Van Eck M, Hoekstra M. PRMT3 inhibitor SGC707 reduces triglyceride levels and induces pruritus in Western- type diet-fed LDL receptor knockout mice. Sci Rep. 2022 Jan 10;12(1):483. doi: 10.1038/s41598-021-04524-w. PMID: 35013582; PMCID: PMC8748717. 9: Hao F, Tang LC, Sun JX, Li WX, Zhao Y, Xu XH, Jin LP. Decreased nitric oxide content mediated by asymmetrical dimethylarginine and protein l-arginine methyltransferase 3 in macrophages induces trophoblast apoptosis: a potential cause of recurrent miscarriage. Hum Reprod. 2021 Nov 18;36(12):3049-3061. doi: 10.1093/humrep/deab225. PMID: 34647126. 10: Zhu J, Liu X, Cai X, Ouyang G, Zha H, Zhou Z, Liao Q, Wang J, Xiao W. Zebrafish prmt3 negatively regulates antiviral responses. FASEB J. 2020 Aug;34(8):10212-10227. doi: 10.1096/fj.201902569R. Epub 2020 Jul 8. PMID: 32643209. 11: Min Z, Xiaomeng L, Zheng L, Yangge D, Xuejiao L, Longwei L, Xiao Z, Yunsong L, Ping Z, Yongsheng Z. Asymmetrical methyltransferase PRMT3 regulates human mesenchymal stem cell osteogenesis via miR-3648. Cell Death Dis. 2019 Aug 5;10(8):581. doi: 10.1038/s41419-019-1815-7. PMID: 31378783; PMCID: PMC6680051. 12: Hoekstra M, Nahon JE, de Jong LM, Kröner MJ, de Leeuw LR, Van Eck M. Inhibition of PRMT3 activity reduces hepatic steatosis without altering atherosclerosis susceptibility in apoE knockout mice. Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1402-1409. doi: 10.1016/j.bbadis.2019.02.012. Epub 2019 Feb 15. PMID: 30776415. 13: Nahon JE, Groeneveldt C, Geerling JJ, van Eck M, Hoekstra M. Inhibition of protein arginine methyltransferase 3 activity selectively impairs liver X receptor-driven transcription of hepatic lipogenic genes in vivo. Br J Pharmacol. 2018 Aug;175(15):3175-3183. doi: 10.1111/bph.14361. Epub 2018 Jun 15. PMID: 29774529; PMCID: PMC6031883. 14: Kaniskan HÜ, Szewczyk MM, Yu Z, Eram MS, Yang X, Schmidt K, Luo X, Dai M, He F, Zang I, Lin Y, Kennedy S, Li F, Dobrovetsky E, Dong A, Smil D, Min SJ, Landon M, Lin-Jones J, Huang XP, Roth BL, Schapira M, Atadja P, Barsyte-Lovejoy D, Arrowsmith CH, Brown PJ, Zhao K, Jin J, Vedadi M. A potent, selective and cell- active allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3). Angew Chem Int Ed Engl. 2015 Apr 20;54(17):5166-70. doi: 10.1002/anie.201412154. Epub 2015 Feb 27. PMID: 25728001; PMCID: PMC4400258.