PAI-039


Catalog No. size PriceQuantity
M6425-2 2mg solid $120
M6425-10 10mg solid $482

Description

Cas:393105-53-8

Product Information

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 Formula: C24H16F3NO4

 

Exact Mass: 439.10314

 

Molecular Weight: 439.38

 

Elemental Analysis: C, 65.60; H, 3.67; F, 12.97; N, 3.19; O, 14.57

 

Synonym:

 

Tiplaxtinin

PAI039

PAI-039

PAI 039

 

Chemical Name: 2-(1-benzyl-5-(4-(trifluoromethoxy)phenyl)-1H-indol-3-yl)-2-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

 

 

Technical Data:

 

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

 

In Vitro:

Tiplaxtinin (PAI-039), a small-molecule inhibitor of PAI-1 activity, on the urothelial cell lines. A significant inhibition in cellular proliferation is noted in T24 cells treated with Tiplaxtinin with the documentation of a favorable IC50 value of 43.7±6.3 μM and in UM-UC-14 cells 52.8±1.6 μM whereas the benign cell line, UROtsa, is noted to have a higher IC50 value of 70.3±0.1 μM. Notably, IC50 values of Tiplaxtinin in detached cells, 19.7±3.8 μM in T24, 44.5±6.5 μM in UM-UC-14, and 31.6±6.1 μM in UROtsa, are significantly lower than the IC50 values calculated for cells cultured in the presence of Tiplaxtinin under attached condition.

 

In Vivo:

In the vena cava protocol, Tiplaxtinin (PAI-039) pretreatment significantly reduces thrombus weight at Tiplaxtinin doses of 3, 10 and 30 mg/kg. When Tiplaxtinin is dosed in a treatment paradigm 4 h after stable arterial and venous thrombosis, a significant reduction in thrombus weight is observed 24 h later at Tiplaxtinin doses of 3, 10 and 30 mg/kg. Tiplaxtinin (PAI-039) is administered by oral gavage to athymic mice bearing human bladder cancer cell line T24 xenografts and human cervical cancer HeLa cell xenografts. The subcutaneous tumor growth of both T24 and HeLa cell xenografts treated with Tiplaxtinin is markedly reduced compared with untreated controls. Specifically, at the end of the study, control T24 xenografts are noted to be 1,150±302 mm3 compared with 593±328 mm3 for T24 xenograft tumors treated with 5 mg/kg Tiplaxtinin (P<0.0001) and 627±248 mm3 for T24 xenografts treated with 20 mg/kg (P<0.0001). Tiplaxtinin (1, 3, and 10 mg/kg) is subjected to electrolytic injury of the coronary artery. Tiplaxtinin (PAI-039) causes prolongation in time to coronary occlusion (control, 31.7±6.3 min; 3 mg/kg Tiplaxtinin, 66.0±6.4 min; 10 mg/kg, 56.7±7.4 min; n=5-6; p<0.05) and a reduced thrombus weight (control, 7.6±1.5 mg; 10 mg/kg Tiplaxtinin, 3.6±1.0 mg; p<0.05).

 

 

References

 

  1. Rebalka IA, Raleigh MJ, D'Souza DM, Coleman SK, Rebalka AN, Hawke TJ. Inhibition of PAI-1 via PAI-039 improves dermal wound closure in diabetes mellitus. Diabetes. 2015 Mar 9. pii: db141174. [Epub ahead of print] PubMed PMID: 25754958.

 

  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. PubMed PMID: 18624980.

 

  1. Hennan JK, Elokdah H, Leal M, Ji A, Friedrichs GS, Morgan GA, Swillo RE, Antrilli TM, Hreha A, Crandall DL. Evaluation of PAI-039 [{1-benzyl-5-[4-(trifluoromethoxy)phenyl]-1H-indol-3-yl}(oxo)acetic acid], a novel plasminogen activator inhibitor-1 inhibitor, in a canine model of coronary artery thrombosis. J Pharmacol Exp Ther. 2005 Aug;314(2):710-6. Epub 2005 Apr 28. PubMed PMID: 15860572.

 

Products are for research use only. Not for human use.

Payment & Security

American Express Apple Pay Diners Club Discover Elo Google Pay JCB Mastercard PayPal Shop Pay Venmo Visa

Your payment information is processed securely. We do not store credit card details nor have access to your credit card information.

Estimate shipping

You may also like

Recently viewed