SH-4-54 | CAS#1456632-40-8 | STAT inhibitor

MedKoo Cat#: 406797 | Name: SH-4-54

Description:

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

SH-4-54 is a potent STAT inhibitor with KD of 300 nM and 464 nM for STAT3 and STAT5, respectively. SH-4-54 potently kills glioblastoma brain cancer stem cells (BTSCs) and effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets at low nM concentrations. Moreover, in vivo,SH-4-54 exhibited blood-brain barrier permeability, potently controlled glioma tumor growth, and inhibited pSTAT3 in vivo.

Chemical Structure

SH-4-54

CAS#1456632-40-8

Theoretical Analysis

MedKoo Cat#: 406797

Name: SH-4-54

CAS#: 1456632-40-8

Chemical Formula: C29H27F5N2O5S

Exact Mass: 610.1561

Molecular Weight: 610.60

Elemental Analysis: C, 57.05; H, 4.46; F, 15.56; N, 4.59; O, 13.10; S, 5.25

Price and Availability

Size	Price	Availability
5mg	USD 300.00	2 Weeks
10mg	USD 500.00	2 Weeks
25mg	USD 800.00	2 Weeks

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Synonym

SH-4-54; SH 4-54; SH4-54; SH-454; SH 454; SH454.

IUPAC/Chemical Name

4-(N-(4-cyclohexylbenzyl)-2-((2,3,4,5,6-pentafluoro-N-methylphenyl)sulfonamido)acetamido)benzoic acid

InChi Key

VFPYGNNOSJWBHF-UHFFFAOYSA-N

InChi Code

InChI=1S/C29H27F5N2O5S/c1-35(42(40,41)28-26(33)24(31)23(30)25(32)27(28)34)16-22(37)36(21-13-11-20(12-14-21)29(38)39)15-17-7-9-19(10-8-17)18-5-3-2-4-6-18/h7-14,18H,2-6,15-16H2,1H3,(H,38,39)

SMILES Code

O=C(O)C1=CC=C(N(CC2=CC=C(C3CCCCC3)C=C2)C(CN(C)S(=O)(C4=C(F)C(F)=C(F)C(F)=C4F)=O)=O)C=C1

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, DMF, and ethanol

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#A23M02B09

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SH-4-54 is an inhibitor of signal transducer and activator of transcription 3 (STAT3; IC50 = 4.7 μM for STAT3 homodimer DNA binding activity). It selectively inhibits STAT3 homodimer over STAT1 and STAT5 homodimer and STAT3:STAT1 heterodimer DNA binding in EGF-stimulated NIH3T3/hEGFR nuclear extracts containing activated STAT1, STAT3, and STAT5 and decreases STAT3 iNOS, Survivin, and Bcl-2 promoter occupancy in MDA-MB-231 cells. SH-4-54 inhibits growth of glioma, breast, and prostate cancer cell lines that express constitutively active STAT3 (IC50s = 1-7.4, 3.8-4.5, and 5.3-5.8 μM, respectively). In vivo, SH-4-54 (3 mg/kg per day) inhibits tumor growth in the U251MG glioma and MDA-MB-231 breast cancer mouse xenograft models.

In vitro activity:

To be determined

In vivo activity:

The results of this study offer preclinical proof of concept for SH5-07 and SH4-54 as candidates for further development as cancer therapeutics. In mouse xenograft models of glioma and breast cancer, administration of SH5-07 or SH4-54 effectively inhibited tumor growth. Reference: Cancer Res. 2016 Feb 1;76(3):652-63. https://pubmed.ncbi.nlm.nih.gov/26088127/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	49.13
	DMSO	30.0	49.13
	Ethanol	20.0	32.75

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 610.60 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. Yue P, Lopez-Tapia F, Paladino D, Li Y, Chen CH, Namanja AT, Hilliard T, Chen Y, Tius MA, Turkson J. Hydroxamic Acid and Benzoic Acid-Based STAT3 Inhibitors Suppress Human Glioma and Breast Cancer Phenotypes In Vitro and In Vivo. Cancer Res. 2016 Feb 1;76(3):652-63. doi: 10.1158/0008-5472.CAN-14-3558. Epub 2015 Jun 18. PMID: 26088127; PMCID: PMC4684502.

In vitro protocol:

To be determined

In vivo protocol:

1: Haftchenary S, Luchman HA, Jouk AO, Veloso AJ, Page BD, Cheng XR, Dawson SS, Grinshtein N, Shahani VM, Kerman K, Kaplan DR, Griffin C, Aman AM, Al-Awar R, Weiss S, Gunning PT. Potent Targeting of the STAT3 Protein in Brain Cancer Stem Cells: A Promising Route for Treating Glioblastoma. ACS Med Chem Lett. 2013 Sep 8;4(11):1102-7. doi: 10.1021/ml4003138. PMID: 24900612; PMCID: PMC4027491. 2: Arpin CC, Mac S, Jiang Y, Cheng H, Grimard M, Page BD, Kamocka MM, Haftchenary S, Su H, Ball DP, Rosa DA, Lai PS, Gómez-Biagi RF, Ali AM, Rana R, Hanenberg H, Kerman K, McElyea KC, Sandusky GE, Gunning PT, Fishel ML. Applying Small Molecule Signal Transducer and Activator of Transcription-3 (STAT3) Protein Inhibitors as Pancreatic Cancer Therapeutics. Mol Cancer Ther. 2016 May;15(5):794-805. doi: 10.1158/1535-7163.MCT-15-0003. Epub 2016 Feb 12. PMID: 26873728; PMCID: PMC4873422. 3: Linher-Melville K, Nashed MG, Ungard RG, Haftchenary S, Rosa DA, Gunning PT, Singh G. Chronic Inhibition of STAT3/STAT5 in Treatment-Resistant Human Breast Cancer Cell Subtypes: Convergence on the ROS/SUMO Pathway and Its Effects on xCT Expression and System xc- Activity. PLoS One. 2016 Aug 11;11(8):e0161202. doi: 10.1371/journal.pone.0161202. PMID: 27513743; PMCID: PMC4981357. 4: Swerev TM, Wirth T, Ushmorov A. Activation of oncogenic pathways in classical Hodgkin lymphoma by decitabine: A rationale for combination with small molecular weight inhibitors. Int J Oncol. 2017 Feb;50(2):555-566. doi: 10.3892/ijo.2016.3827. Epub 2016 Dec 30. PMID: 28035374. 5: Cheng Y, Hao Y, Zhang A, Hu C, Jiang X, Wu Q, Xu X. Persistent STAT5-mediated ROS production and involvement of aberrant p53 apoptotic signaling in the resistance of chronic myeloid leukemia to imatinib. Int J Mol Med. 2018 Jan;41(1):455-463. doi: 10.3892/ijmm.2017.3205. Epub 2017 Oct 20. PMID: 29115375. 6: Herrera-Perez RM, Voytik-Harbin SL, Sarkaria JN, Pollok KE, Fishel ML, Rickus JL. Presence of stromal cells in a bioengineered tumor microenvironment alters glioblastoma migration and response to STAT3 inhibition. PLoS One. 2018 Mar 22;13(3):e0194183. doi: 10.1371/journal.pone.0194183. PMID: 29566069; PMCID: PMC5863989. 7: Cummins CB, Wang X, Nunez Lopez O, Graham G, Tie HY, Zhou J, Radhakrishnan RS. Luteolin-Mediated Inhibition of Hepatic Stellate Cell Activation via Suppression of the STAT3 Pathway. Int J Mol Sci. 2018 May 24;19(6):1567. doi: 10.3390/ijms19061567. PMID: 29795016; PMCID: PMC6032316. 8: Memarzadeh K, Savage DJ, Bean AJ. Low UBE4B expression increases sensitivity of chemoresistant neuroblastoma cells to EGFR and STAT5 inhibition. Cancer Biol Ther. 2019;20(12):1416-1429. doi: 10.1080/15384047.2019.1647049. Epub 2019 Sep 1. PMID: 31475882; PMCID: PMC6804809. 9: Hindupur SV, Schmid SC, Koch JA, Youssef A, Baur EM, Wang D, Horn T, Slotta- Huspenina J, Gschwend JE, Holm PS, Nawroth R. STAT3/5 Inhibitors Suppress Proliferation in Bladder Cancer and Enhance Oncolytic Adenovirus Therapy. Int J Mol Sci. 2020 Feb 7;21(3):1106. doi: 10.3390/ijms21031106. PMID: 32046095; PMCID: PMC7043223. 10: Zhu M, Yang M, Yang Q, Liu W, Geng H, Pan L, Wang L, Ge R, Ji L, Cui S, Li Z. Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6/JAK2/STAT3/MMP-9 Pathway. Biomed Res Int. 2020 Jan 23;2020:9204708. doi: 10.1155/2020/9204708. PMID: 32047820; PMCID: PMC7003287. 11: Cui P, Wei F, Hou J, Su Y, Wang J, Wang S. STAT3 inhibition induced temozolomide-resistant glioblastoma apoptosis via triggering mitochondrial STAT3 translocation and respiratory chain dysfunction. Cell Signal. 2020 Jul;71:109598. doi: 10.1016/j.cellsig.2020.109598. Epub 2020 Mar 9. PMID: 32165236. 12: Ji X, Guo X, Wang Y, Li X, Li H. Rab18 Regulates Proliferation, Invasion and Cisplatin Sensitivity Through STAT3 Signaling in Head and Neck Squamous Cell Carcinoma. Onco Targets Ther. 2020 May 13;13:4123-4134. doi: 10.2147/OTT.S238503. PMID: 32494165; PMCID: PMC7231766. 13: Wang C, Li L, Li M, Shen X, Liu Y, Wang S. Inactivated STAT5 pathway underlies a novel inhibitory role of EBF1 in chronic lymphocytic leukemia. Exp Cell Res. 2021 Jan 1;398(1):112371. doi: 10.1016/j.yexcr.2020.112371. Epub 2020 Nov 11. Erratum in: Exp Cell Res. 2021 Mar 1;400(1):112469. doi: 10.1016/j.yexcr.2020.112469. PMID: 33188849. 14: Jia ZX, Lu XZ, He JY, Cai XH, Qin W, Han WM, Zhou M, Xu W. [Mechanism of Anti Apoptosis and Immune Evasion in Drug-Resistant Leukemia Cells Mediated by STAT3]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Dec;28(6):1796-1803. Chinese. doi: 10.19746/j.cnki.issn.1009-2137.2020.06.002. PMID: 33283701. 15: Qin L, Qiao C, Sheen V, Wang Y, Lu J. DNMT3L promotes neural differentiation by enhancing STAT1 and STAT3 phosphorylation independent of DNA methylation. Prog Neurobiol. 2021 Jun;201:102028. doi: 10.1016/j.pneurobio.2021.102028. Epub 2021 Feb 23. PMID: 33636226. 16: Zhang Y, Yuan P, Ma X, Deng Q, Gao J, Yang J, Zhang T, Zhang C, Zhang W. Deletion of Smooth Muscle Lethal Giant Larvae 1 Promotes Neointimal Hyperplasia in Mice. Front Pharmacol. 2022 Jan 24;13:834296. doi: 10.3389/fphar.2022.834296. PMID: 35140622; PMCID: PMC8819082. 17: Sun Y, Dong Y, Liu X, Zhang Y, Bai H, Duan J, Tian Z, Yan X, Wang J, Wang Z. Blockade of STAT3/IL-4 overcomes EGFR T790M-cis-L792F-induced resistance to osimertinib via suppressing M2 macrophages polarization. EBioMedicine. 2022 Sep;83:104200. doi: 10.1016/j.ebiom.2022.104200. Epub 2022 Aug 3. PMID: 35932642; PMCID: PMC9358434. 18: Yin L, Xu J, Wu W, Niu M, Li Z, Zhu F, Xu K. Dual inhibition of STAT3 and STAT5 may overcome imatinib resistance in chronic myeloid leukemia. Hematology. 2023 Dec;28(1):2224625. doi: 10.1080/16078454.2023.2224625. PMID: 37345979. 19: Yu D, Wang S, Wang J, Zhang K, Niu Z, Lin N. EZH2-STAT3 signaling pathway regulates GSDMD-mediated pyroptosis in glioblastoma. Cell Death Discov. 2024 Jul 28;10(1):341. doi: 10.1038/s41420-024-02105-0. PMID: 39069522; PMCID: PMC11284224.