TM-5275 sodium | CAS#1103926-82-4 | PAI-1 inhibitor

MedKoo Cat#: 523107 | Name: TM-5275 sodium

Description:

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

TM 5275 sodium salt is an orally bioavailable plasminogen activator inhibitor-1 (PAI-1) inhibitor.

Chemical Structure

TM-5275 sodium

CAS#1103926-82-4 (sodium)

Theoretical Analysis

MedKoo Cat#: 523107

Name: TM-5275 sodium

CAS#: 1103926-82-4 (sodium)

Chemical Formula: C28H27ClN3NaO5

Exact Mass: 543.1537

Molecular Weight: 543.98

Elemental Analysis: C, 61.82; H, 5.00; Cl, 6.52; N, 7.72; Na, 4.23; O, 14.71

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 650.00	Ready to ship
200mg	USD 1,050.00	Ready to ship
500mg	USD 1,950.00	Ready to ship
1g	USD 2,950.00	Ready to ship
2g	USD 5,250.00	Ready to ship

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Related CAS #

1103928-13-7 (free acid) 1103926-82-4 (sodium)

Synonym

TM5275 sodium salt; TM-5275 sodium salt; TM 5275 sodium salt.

IUPAC/Chemical Name

5-Chloro-2-[[2-[2-[4-(Diphenylmethyl)-1-piperazinyl]-2-oxoethoxy]acetyl]amino]benzoic acid sodium salt

InChi Key

JSHSGBIWNPQCQZ-UHFFFAOYSA-M

InChi Code

InChI=1S/C28H28ClN3O5.Na/c29-22-11-12-24(23(17-22)28(35)36)30-25(33)18-37-19-26(34)31-13-15-32(16-14-31)27(20-7-3-1-4-8-20)21-9-5-2-6-10-21;/h1-12,17,27H,13-16,18-19H2,(H,30,33)(H,35,36);/q;+1/p-1

SMILES Code

O=C([O-])C1=CC(Cl)=CC=C1NC(COCC(N2CCN(C(C3=CC=CC=C3)C4=CC=CC=C4)CC2)=O)=O.[Na+]

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#A21T08K04

QC Data

View QC data: current batch, Lot#A21T08K04

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

TM5275 is an inhibitor of plasminogen activator inhibitor 1 (PAI-1; IC50 = 6.95 µM).

In vitro activity:

LPS-treated macrophages were adopted as an in vitro model of endotoxin-induced inflammation during sepsis. Experiments were carried out using primary mouse peritoneal macrophages and the murine macrophage cell line RAW264.7, to elucidate the mechanisms by which HDAC2 modulates endotoxin-induced inflammation. Results revealed that PAI-1, TNF, and MIP-2 expression were inhibited by theophylline, an HDAC2 enhancer, in a RAW macrophage cell line, following LPS-induced inflammation. Thus, HDAC2 plays an important role in immune defense by regulating the expression of inflammatory genes via the c-Jun/PAI-1 pathway. During LPS-induced inflammation, overexpression of HDAC2 was found to inhibit PAI-1, TNF, and MIP-2 expression. Following LPS stimulation, HDAC2 knockdown increased nuclear translocation and DNA binding of c-Jun to the PAI-1 gene promoter, thereby activating PAI-1 gene transcription. Furthermore, inhibition of PAI-1 by TM5275 alone or in combination with theophylline notably suppressed TNF and MIP-2 expression. HDAC2 can attenuate lipopolysaccharide-induced inflammation by regulating c-Jun and PAI-1 expression in macrophages. Reference:Fang WF, Chen YM, Lin CY, Huang HL, Yeh H, Chang YT, Huang KT, Lin MC. Histone deacetylase 2 (HDAC2) attenuates lipopolysaccharide (LPS)-induced inflammation by regulating PAI-1 expression. J Inflamm (Lond). 2018 Jan 10;15:3. doi: 10.1186/s12950-018-0179-6. PMID: 29344006; PMCID: PMC5763578.

In vivo activity:

The current study was designed to explicate the effect of TM5275, an oral PAI‑1 inhibitor, on MetS‑related hepatic fibrogenesis. The in vivo antifibrotic effect of orally administered TM5275 was investigated in two different rat MetS models. Fischer 344 rats received a choline‑deficient L‑amino‑acid‑defined diet for 12 weeks to induce steatohepatitis with development of severe hepatic fibrosis. Otsuka Long‑Evans Tokushima Fatty rats, used to model congenital diabetes, underwent intraperitoneal injection of porcine serum for 6 weeks to induce hepatic fibrosis under diabetic conditions. In each experimental model, TM5275 markedly ameliorated the development of hepatic fibrosis and suppressed the proliferation of activated hepatic stellate cells (HSCs). Additionally, the hepatic production of tumor growth factor (TGF)‑β1 and total collagen was suppressed. In vitro assays revealed that TGF‑β1 stimulated the upregulation of Serpine1 mRNA expression, which was inhibited by TM5275 treatment in cultured HSC‑T6 cells, a rat HSC cell line. Furthermore, TM5275 substantially attenuated the TGF‑β1‑stimulated proliferative and fibrogenic activity of HSCs by inhibiting AKT phosphorylation. Collectively, TM5275 demonstrated an antifibrotic effect on liver fibrosis in different rat MetS models, suppressing TGF‑β1‑induced HSC proliferation and collagen synthesis. Thus, PAI‑1 inhibitors may serve as effective future therapeutic agents against NASH‑based hepatic fibrosis. Reference: Noguchi R, Kaji K, Namisaki T, Moriya K, Kawaratani H, Kitade M, Takaya H, Aihara Y, Douhara A, Asada K, Nishimura N, Miyata T, Yoshiji H. Novel oral plasminogen activator inhibitor‑1 inhibitor TM5275 attenuates hepatic fibrosis under metabolic syndrome via suppression of activated hepatic stellate cells in rats. Mol Med Rep. 2020 Oct;22(4):2948-2956. doi: 10.3892/mmr.2020.11360. Epub 2020 Jul 28. PMID: 32945412; PMCID: PMC7453658.

	Solvent	mg/mL	mM
Solubility
	DMSO	20.0	36.77
	DMF:PBS (pH 7.2) (1:8)	0.1	0.20
	DMF	33.0	60.66

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 543.98 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:

Fang WF, Chen YM, Lin CY, Huang HL, Yeh H, Chang YT, Huang KT, Lin MC. Histone deacetylase 2 (HDAC2) attenuates lipopolysaccharide (LPS)-induced inflammation by regulating PAI-1 expression. J Inflamm (Lond). 2018 Jan 10;15:3. doi: 10.1186/s12950-018-0179-6. PMID: 29344006; PMCID: PMC5763578.

In vitro protocol:

In vivo protocol:

Noguchi R, Kaji K, Namisaki T, Moriya K, Kawaratani H, Kitade M, Takaya H, Aihara Y, Douhara A, Asada K, Nishimura N, Miyata T, Yoshiji H. Novel oral plasminogen activator inhibitor‑1 inhibitor TM5275 attenuates hepatic fibrosis under metabolic syndrome via suppression of activated hepatic stellate cells in rats. Mol Med Rep. 2020 Oct;22(4):2948-2956. doi: 10.3892/mmr.2020.11360. Epub 2020 Jul 28. PMID: 32945412; PMCID: PMC7453658.

Sharma M, Shetty SS, Radhakrishnan R. Oral Submucous Fibrosis as an Overhealing Wound: Implications in Malignant Transformation. Recent Pat Anticancer Drug Discov. 2018;13(3):272-291. doi: 10.2174/1574892813666180227103147. PMID: 29485009.