T-5224 | CAS#530141-72-1 | AP-1 Inhibitor

MedKoo Cat#: 206216 | Name: T-5224

Description:

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

T-5224 is a selective inhibitor of c-Fos/activator protein-1. T-5224 ameliorates liver injury and improves survival through decreasing production of proinflammatory cytokines and chemokines in endotoxemic mice. T-5224 has been investigated in phase II human clinical trials. T-5224 may be a promising new treatment for septic kidney injury. Activator protein 1 (AP-1) is a pivotal transcription factor that regulates a wide range of cellular processes including proliferation, apoptosis, differentiation, survival, cell migration, and transformation.

Chemical Structure

T-5224

CAS#530141-72-1

Theoretical Analysis

MedKoo Cat#: 206216

Name: T-5224

CAS#: 530141-72-1

Chemical Formula: C29H27NO8

Exact Mass: 517.1737

Molecular Weight: 517.53

Elemental Analysis: C, 67.30; H, 5.26; N, 2.71; O, 24.73

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 300.00	Ready to ship
50mg	USD 550.00	Ready to ship
100mg	USD 950.00	Ready to ship
200mg	USD 1,750.00	Ready to ship

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Related CAS #

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Synonym

T5224, T-5224, T 5224

IUPAC/Chemical Name

3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxybenzo[d]isoxazol-6-yl)methoxy)phenyl)propanoic acid

InChi Key

DALCQQSLNPLQFZ-UHFFFAOYSA-N

InChi Code

InChI=1S/C29H27NO8/c31-24-15-21(37-20-3-1-2-4-20)8-10-22(24)28(34)19-6-11-25(18(14-19)7-12-27(32)33)36-16-17-5-9-23-26(13-17)38-30-29(23)35/h5-6,8-11,13-15,20,31H,1-4,7,12,16H2,(H,30,35)(H,32,33)

SMILES Code

O=C(O)CCC1=CC(C(C2=CC=C(OC3CCCC3)C=C2O)=O)=CC=C1OCC4=CC5=C(C=C4)C(O)=NO5

Appearance

White to off-white crystalline solid

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#N7L08C11

QC Data

View QC data: current batch, Lot#N7L08C11

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

T-5224 is a transcription factor c-Fos/activator protein (AP)-1 inhibitor.

In vitro activity:

T-5224, was newly generated from a cyclic disulfide decapeptide designed by 3D pharmacophore modeling based on the X-ray crystal structure of the basic region–leucine zipper domain of the AP-1–DNA complex. IL-1β treatment of human NP cells significantly increased the expression of c-Fos mRNA in human NP cells, and the levels of c-Fos in the nucleus increased with time (Fig. 1a–c). Further, the levels of MMP-3, MMP-13, ADAMTS-5 and IL-1β mRNAs were significantly increased by IL-1β treatment and significantly decreased by T-5224 in a dose-dependent manner (Fig. 1d). Inhibition of the IL-1β induced up-regulation of MMP-3 and -13 by T-5224 was apparent in immunofluorescence staining (Fig. 1e). Reference: Sci Rep. 2017; 7: 16983. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717052/

In vivo activity:

HMGB-1 is a late mediator of lethal systemic inflammation in animal models of cytokine-mediated sepsis. Activated macrophages release HMGB-1 after a lag of 12–18 h. Serum HMGB-1 concentration 18 h after LPS injection was significantly higher than that of controls (Table 1), and oral administration of T-5224 immediately after LPS injection inhibited serum HMGB-1 increases. Survival rates at 72 h post-LPS injection were 40 % (Fig. 1). However, in mice treated with T-5224, survival rates at the corresponding time point after LPS injection increased to 80 % (Fig. 1, P < 0.01). Reference: J Intensive Care. 2015; 3: 49. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647501/

	Solvent	mg/mL	mM
Solubility
	DMSO	30.5	58.93
	DMSO:PBS (pH 7.2) (1:2)	0.3	0.64
	DMF	30.0	57.97

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 517.53 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. Makino H, Seki S, Yahara Y, Shiozawa S, Aikawa Y, Motomura H, Nogami M, Watanabe K, Sainoh T, Ito H, Tsumaki N, Kawaguchi Y, Yamazaki M, Kimura T. A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain. Sci Rep. 2017 Dec 5;7(1):16983. doi: 10.1038/s41598-017-17289-y. PMID: 29208967; PMCID: PMC5717052. 2. Avouac J, Palumbo K, Tomcik M, Zerr P, Dees C, Horn A, Maurer B, Akhmetshina A, Beyer C, Sadowski A, Schneider H, Shiozawa S, Distler O, Schett G, Allanore Y, Distler JH. Inhibition of activator protein 1 signaling abrogates transforming growth factor β-mediated activation of fibroblasts and prevents experimental fibrosis. Arthritis Rheum. 2012 May;64(5):1642-52. doi: 10.1002/art.33501. PMID: 22139817. 3. Kamide D, Yamashita T, Araki K, Tomifuji M, Tanaka Y, Tanaka S, Shiozawa S, Shiotani A. Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model. Cancer Sci. 2016 May;107(5):666-73. doi: 10.1111/cas.12914. Epub 2016 Apr 26. PMID: 26918517; PMCID: PMC4970834. 4. Ishida M, Ueki M, Morishita J, Ueno M, Shiozawa S, Maekawa N. T-5224, a selective inhibitor of c-Fos/activator protein-1, improves survival by inhibiting serum high mobility group box-1 in lethal lipopolysaccharide-induced acute kidney injury model. J Intensive Care. 2015 Nov 14;3:49. doi: 10.1186/s40560-015-0115-2. PMID: 26579229; PMCID: PMC4647501.

In vitro protocol:

In vivo protocol:

1. Kamide D, Yamashita T, Araki K, Tomifuji M, Tanaka Y, Tanaka S, Shiozawa S, Shiotani A. Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model. Cancer Sci. 2016 May;107(5):666-73. doi: 10.1111/cas.12914. Epub 2016 Apr 26. PMID: 26918517; PMCID: PMC4970834. 2. Ishida M, Ueki M, Morishita J, Ueno M, Shiozawa S, Maekawa N. T-5224, a selective inhibitor of c-Fos/activator protein-1, improves survival by inhibiting serum high mobility group box-1 in lethal lipopolysaccharide-induced acute kidney injury model. J Intensive Care. 2015 Nov 14;3:49. doi: 10.1186/s40560-015-0115-2. PMID: 26579229; PMCID: PMC4647501.

1: Tang S, Liu J, Li F, Yan Y, Long X, Fu Y. AP-1 inhibitor induces ferroptosis via the PI3K/AKT pathway in multiple myeloma cells. Heliyon. 2024 Jul 10;10(14):e34397. doi: 10.1016/j.heliyon.2024.e34397. PMID: 39104494; PMCID: PMC11298940. 2: Khanal P, Patil VS, Bhattacharya K, Shrivastava AK, Bhandare VV. Exploring the globoid cell leukodystrophy protein network and therapeutic interventions. Sci Rep. 2024 Aug 5;14(1):18067. doi: 10.1038/s41598-024-66437-8. PMID: 39103379; PMCID: PMC11300594. 3: Zaman SU, Pagare PP, Huang B, Rilee G, Ma Z, Zhang Y, Li J. Novel PROTAC probes targeting FOSL1 degradation to eliminate head and neck squamous cell carcinoma cancer stem cells. Bioorg Chem. 2024 Oct;151:107613. doi: 10.1016/j.bioorg.2024.107613. Epub 2024 Jul 9. PMID: 39002513; PMCID: PMC11365795. 4: Khan AW, Aziz M, Sourris KC, Lee MKS, Dai A, Watson AMD, Maxwell S, Sharma A, Zhou Y, Cooper ME, Calkin AC, Murphy AJ, Baratchi S, Jandeleit-Dahm KAM. The Role of Activator Protein-1 Complex in Diabetes-Associated Atherosclerosis: Insights From Single-Cell RNA Sequencing. Diabetes. 2024 Sep 1;73(9):1495-1512. doi: 10.2337/db23-0167. PMID: 38905153. 5: Wang H, Ma C, Liu C, Sun L, Wang Y, Xue J, Zhao B, Dong W. The c-Fos/AP-1 inhibitor inhibits sulfur mustard-induced chondrogenesis impairment in zebrafish larvae. Chemosphere. 2024 Jul;359:142299. doi: 10.1016/j.chemosphere.2024.142299. Epub 2024 May 16. PMID: 38761826. 6: Zhang Z, Liu D, Lv R, Zhao H, Li T, Huang Y, Tian Z, Gao X, Luo P, Li X. FBL Promotes LPS-Induced Neuroinflammation by Activating the NF-κB Signaling Pathway. J Inflamm Res. 2024 Apr 11;17:2217-2231. doi: 10.2147/JIR.S451049. PMID: 38623466; PMCID: PMC11018134. 7: Sasakura M, Urakami H, Tachibana K, Ikeda K, Hasui KI, Matsuda Y, Sunagawa K, Ennishi D, Tomida S, Morizane S. Topical application of activator protein-1 inhibitor T-5224 suppresses inflammation and improves skin barrier function in a murine atopic dermatitis-like dermatitis. Allergol Int. 2024 Apr;73(2):323-331. doi: 10.1016/j.alit.2023.12.006. Epub 2024 Feb 12. PMID: 38350816. 8: Guo Z, Zhu Y, Xiao H, Dai R, Yang W, Xue W, Zhang X, Hao B, Liao S. Integration of ATAC-seq and RNA-seq identifies MX1-mediated AP-1 transcriptional regulation as a therapeutic target for Down syndrome. Biol Res. 2023 Dec 9;56(1):67. doi: 10.1186/s40659-023-00474-x. PMID: 38066591; PMCID: PMC10709892. 9: Watanabe N, Tamai R, Kiyoura Y. Alendronate augments lipid A‑induced IL‑1β release by ASC‑deficient RAW264 cells via AP‑1 activation. Exp Ther Med. 2023 Oct 26;26(6):577. doi: 10.3892/etm.2023.12276. PMID: 38023354; PMCID: PMC10655061. 10: Luo Y, Luo J, An P, Zhao Y, Zhao W, Fang Z, Xia Y, Zhu L, Xu T, Zhang X, Zhou S, Yang M, Li J, Zhu J, Liu Y, Li H, Gong M, Liu Y, Han J, Guo H, Zhang H, Jiang W, Ren F. The activator protein-1 complex governs a vascular degenerative transcriptional programme in smooth muscle cells to trigger aortic dissection and rupture. Eur Heart J. 2024 Jan 27;45(4):287-305. doi: 10.1093/eurheartj/ehad534. PMID: 37992083. 11: Yuan J, Li G, Zhong F, Liao J, Zeng Z, Ouyang S, Xie H, Deng Z, Tang H, Ou X. SALL1 promotes proliferation and metastasis and activates phosphorylation of p65 and JUN in colorectal cancer cells. Pathol Res Pract. 2023 Oct;250:154827. doi: 10.1016/j.prp.2023.154827. Epub 2023 Sep 20. PMID: 37741137. 12: Tang S, Zhang F, Li J, Dong H, Yang Q, Liu J, Fu Y. The selective activator protein-1 inhibitor T-5224 regulates the IRF4/MYC axis and exerts cooperative antimyeloma activity with bortezomib. Chem Biol Interact. 2023 Oct 1;384:110687. doi: 10.1016/j.cbi.2023.110687. Epub 2023 Aug 31. PMID: 37657595. 13: Luo Y, Kang J, Luo J, Yan Z, Li S, Lu Z, Song Y, Zhang X, Yang J, Liu A. Hepatocytic AP-1 and STAT3 contribute to chemotaxis in alphanaphthylisothiocyanate-induced cholestatic liver injury. Toxicol Lett. 2023 Jan 15;373:184-193. doi: 10.1016/j.toxlet.2022.11.020. Epub 2022 Nov 29. PMID: 36460194. 14: Zhao S, Li B, Zhao R, Pan Z, Zhang S, Qiu W, Guo Q, Qi Y, Gao Z, Fan Y, Xu H, Li M, Zhang J, Wang H, Xu J, Wang S, Wang Q, Qiu J, Deng L, Guo X, Zhang P, Xue H, Li G. Hypoxia-induced circADAMTS6 in a TDP43-dependent manner accelerates glioblastoma progression via ANXA2/ NF-κB pathway. Oncogene. 2023 Jan;42(2):138-153. doi: 10.1038/s41388-022-02542-0. Epub 2022 Nov 17. PMID: 36396726. 15: Oh KK, Adnan M, Cho DH. New Insight into Drugs to Alleviate Atopic March via Network Pharmacology-Based Analysis. Curr Issues Mol Biol. 2022 May 18;44(5):2257-2274. doi: 10.3390/cimb44050153. PMID: 35678682; PMCID: PMC9164039. 16: Zhang H, Pei L, Ouyang Z, Wang H, Chen X, Jiang K, Huang S, Jiang R, Xiang Y, Wei K. AP-1 activation mediates post-natal cardiomyocyte maturation. Cardiovasc Res. 2023 Mar 31;119(2):536-550. doi: 10.1093/cvr/cvac088. PMID: 35640820. 17: Li X, Zhou B, Yang H, Yang X, Zhao Z, Pan Z, Liao X, Jian W, Liu Y, Lu H, Xue Q, Luo Y, Yu B, Huang H, Ma D, Liu Z. Phosphorylation at Ser 727 Increases STAT3 Interaction with PKCε Regulating Neuron-Glia Crosstalk via IL-6-Mediated Hyperalgesia In Vivo and In Vitro. Mediators Inflamm. 2022 Jan 28;2022:2782080. doi: 10.1155/2022/2782080. PMID: 35125963; PMCID: PMC8816592. 18: Zhou L, Xue C, Chen Z, Jiang W, He S, Zhang X. c-Fos is a mechanosensor that regulates inflammatory responses and lung barrier dysfunction during ventilator- induced acute lung injury. BMC Pulm Med. 2022 Jan 6;22(1):9. doi: 10.1186/s12890-021-01801-2. PMID: 34986829; PMCID: PMC8734268. 19: Hao Q, Li J, Zhang Q, Xu F, Xie B, Lu H, Wu X, Zhou X. Single-cell transcriptomes reveal heterogeneity of high-grade serous ovarian carcinoma. Clin Transl Med. 2021 Aug;11(8):e500. doi: 10.1002/ctm2.500. PMID: 34459128; PMCID: PMC8335963. 20: de la Peña JB, Kunder N, Lou TF, Chase R, Stanowick A, Barragan-Iglesias P, Pancrazio JJ, Campbell ZT. A role for translational regulation by S6 kinase and a downstream target in inflammatory pain. Br J Pharmacol. 2021 Dec;178(23):4675-4690. doi: 10.1111/bph.15646. Epub 2021 Sep 12. PMID: 34355805; PMCID: PMC9169231.