Tiplasinin | CAS# 393105-53-8 | inhibitor of plasminogen activator inhibitor-1

MedKoo Cat#: 414736 | Name: Tiplasinin free acid

Description:

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

Tiplaxtinin, also known as PAI-039, is a novel plasminogen activator inhibitor-1 (PAI-1) inhibitor. The pharmacokinetic profile of PAI-039 indicated an oral bioavailability of 43 +/- 15.3% and a plasma half-life of 6.2 +/- 1.3 h. PAI-039 is an orally active prothrombolytic drug that inhibits PAI-1 and accelerates fibrinolysis while maintaining normal coagulation in a model of coronary occlusion . PAI-039 exerts antithrombotic efficacy in rat models of arterial and venous vascular injury without effecting platelet aggregation. PAI-039 as a novel therapeutic may improve diabetic wound closure.

Chemical Structure

Tiplasinin free acid

CAS#393105-53-8 (free acid)

Theoretical Analysis

MedKoo Cat#: 414736

Name: Tiplasinin free acid

CAS#: 393105-53-8 (free acid)

Chemical Formula: C24H16F3NO4

Exact Mass: 439.1031

Molecular Weight: 439.39

Elemental Analysis: C, 65.61; H, 3.67; F, 12.97; N, 3.19; O, 14.56

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,350.00	2 Weeks
500mg	USD 2,850.00	2 Weeks
1g	USD 3,850.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Related CAS #

393105-53-8 (free acid) Tiplaxtinin sodium

Synonym

Tiplasinin; PAI039; PAI 039; PAI-039; Tiplaxtinin

IUPAC/Chemical Name

(1-benzyl-5-(4-(trifluoromethoxy)phenyl)-1H-indol-3-yl)oxoacetic acid

InChi Key

ODXQFEWQSHNQNI-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H16F3NO4/c25-24(26,27)32-18-9-6-16(7-10-18)17-8-11-21-19(12-17)20(22(29)23(30)31)14-28(21)13-15-4-2-1-3-5-15/h1-12,14H,13H2,(H,30,31)

SMILES Code

O=C(O)C(C1=CN(CC2=CC=CC=C2)C3=C1C=C(C4=CC=C(OC(F)(F)F)C=C4)C=C3)=O

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

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

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

Instruction

View handling instruction

Biological target:

Tiplasinin is an efficacious inhibitor of plasminogen activator inhibitor-1 (PAI-1) with IC50 of 2.7 μM.

In vitro activity:

To study the interaction between FtsZ and tiplaxtinin, S. aureus FtsZ proteins were cloned, overexpressed, and purified, and some biochemical assays were employed. The results show that tiplaxtinin is able to enhance FtsZ polymerization in a concentration-dependent manner, which is similar to the reported FtsZ-targeting compounds.Methicillin was used in this assay as a non-FtsZ-targeting control antibiotic and it does not influence FtsZ polymerization. The impact of tiplaxtinin on FtsZ polymer formation was further visualized by using transmission electron microscopy (TEM). Moreover, the effect of tiplaxtinin on the GTPase activity of FtsZ was studied. The results show that tiplaxtinin decreases the rate of GTP hydrolysis of FtsZ in a concentration-dependent manner. The result indicates that tiplaxtinin inhibits the rate of GTP hydrolysis of FtsZ, which may be due to the disruption of the assembly of FtsZ. Furthermore, tiplaxtinin displays potent antibacterial activity against Gram-positive pathogenic bacteria including drug-resistant strains: MRSA and VREF. Reference: Medchemcomm. 2017 Aug 22;8(10):1909-1913. https://pubmed.ncbi.nlm.nih.gov/30108711/

In vivo activity:

To assess efficacy in a thrombosis prevention paradigm, PAI-039 was administered orally 90 min before injury (1-30 mg kg(-1)). To assess efficacy in a thrombosis treatment paradigm, vascular injury and stable thrombus formation were followed 4 h later by recovery and PAI-039 administration. PAI-039 prevented carotid artery occlusion in 20, 68 and 60% of animals pretreated with 0.3, 1.0 and 3.0 mg kg(-1), respectively. Time to occlusive thrombosis was increased from 18.2 +/- 4.6 min in controls to 32.5 +/- 8.7 (P = ns), 46.1 +/- 7.0 (P < 0.05), and 41.6 +/- 11.3 min (P < 0.05) in the respective PAI-039 treatment groups. In the vena cava protocol, PAI-039 pretreatment significantly reduced thrombus weight at PAI-039 doses of 3, 10 and 30 mg kg(-1). When PAI-039 was dosed in a treatment paradigm 4 h after stable arterial and venous thrombosis, a significant reduction in thrombus weight was observed 24 h later at PAI-039 doses of 3, 10 and 30 mg kg(-1). PAI-039 (10, 30 and 100 mg kg(-1)) had no effect on platelet aggregation in response to ADP or collagen and was not associated with increased bleeding or prolonged prothrombin time. In animals bearing no vascular injury, PAI-039 had no effect on circulating, low-levels of PAI-1 activity. In contrast, circulating PAI-1 activity increased 5-fold following the induction of vascular injury, which was completely neutralized by PAI-039. In conclusion, PAI-039 exerts antithrombotic efficacy in rat models of arterial and venous vascular injury without effecting platelet aggregation. Reference: J Thromb Haemost. 2008 Sep;6(9):1558-64. https://pubmed.ncbi.nlm.nih.gov/18624980/

	Solvent	mg/mL	mM
Solubility
	DMSO	71.0	161.59

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 439.39 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:

https://pubmed.ncbi.nlm.nih.gov/30108711/ 3. . Hennan JK, Morgan GA, Swillo RE, Antrilli TM, Mugford C, Vlasuk GP, Gardell SJ, Crandall DL. Effect of tiplaxtinin (PAI-039), an orally bioavailable PAI-1 antagonist, in a rat model of thrombosis. J Thromb Haemost. 2008 Sep;6(9):1558-64. doi: 10.1111/j.1538-7836.2008.03063.x. Epub 2008 Jul 4. PMID: 18624980. 4. . Lijnen HR, Alessi MC, Frederix L, Collen D, Juhan-Vague I. Tiplaxtinin impairs nutritionally induced obesity in mice. Thromb Haemost. 2006 Dec;96(6):731-7. PMID: 17139366.

In vitro protocol:

https://pubmed.ncbi.nlm.nih.gov/30108711/

In vivo protocol:

1. Hennan JK, Morgan GA, Swillo RE, Antrilli TM, Mugford C, Vlasuk GP, Gardell SJ, Crandall DL. Effect of tiplaxtinin (PAI-039), an orally bioavailable PAI-1 antagonist, in a rat model of thrombosis. J Thromb Haemost. 2008 Sep;6(9):1558-64. doi: 10.1111/j.1538-7836.2008.03063.x. Epub 2008 Jul 4. PMID: 18624980. 2. Lijnen HR, Alessi MC, Frederix L, Collen D, Juhan-Vague I. Tiplaxtinin impairs nutritionally induced obesity in mice. Thromb Haemost. 2006 Dec;96(6):731-7. PMID: 17139366.

1: Ahmad A, Ahad A, Rao AQ, Husnain T. Molecular docking based screening of neem-derived compounds with the NS1 protein of Influenza virus. Bioinformation. 2015 Jul 31;11(7):359-65. doi: 10.6026/97320630011359. PMID: 26339153; PMCID: PMC4546996. Jin J, Liu Y, Tang Q, Yan X, Jiang M, Zhao X, Chen J, Jin C, Ou Q, Zhao J. Bioinformatics-integrated screening of systemic sclerosis-specific expressed markers to identify therapeutic targets. Front Immunol. 2023 Mar 30;14:1125183. doi: 10.3389/fimmu.2023.1125183. PMID: 37063926; PMCID: PMC10098096.