A4077-100mg | BIBR 953 (Dabigatran, Pradaxa) [211914-51-1] Clinisciences

Background

BIBR 953 is a potent, reversible, and direct inhibitor of thrombin with IC50 value of 9.3nM [1].

BIBR 953 shows a favorable selectivity profile and strong activity in vitro with a Ki value of 4.5nM. It also exhibits the best activity profile in vivo following administration to rats. BIBR 953 is designed to be converted into an orally active prodrug BIBR 1048 due to its highly polar, zwitterionic nature and poor oral absorption. BIBR 953 inhibits thrombin in a competitive fashion. This inhibition is rapid and reversible. BIBR 953 inhibits both clot-bound and free thrombin. BIBR 953 is demonstrated to have an anticoagulant efficacy both in vitro and ex vivo. Since thrombin can affect cell behavior and response in various tissue types via PAR signaling, BIBR 953 is found to be beneficial in many diseases including inflammation, infection, fibrosis and cancer. Clinical trials show that BIBR 953 is a highly effective anticoagulant with a good safety profile [1, 2].

References:
[1] Hauel NH, Nar H, Priepke H, Ries U, Stassen JM, Wienen W. Structure-based design of novel potent nonpeptide thrombin inhibitors. J Med Chem. 2002 Apr 25;45(9):1757-66.
[2] van Ryn J, Goss A, Hauel N, Wienen W, Priepke H, Nar H, Clemens A. The discovery of dabigatran etexilate. Front Pharmacol. 2013 Feb 12;4:12.

Chemical Properties

Storage	Store at -20°C
M.Wt	471.5
Cas No.	211914-51-1
Formula	C₂₅H₂₅N₇O₃
Solubility	insoluble in DMSO; insoluble in EtOH; insoluble in H2O
Chemical Name	3-[[2-[(4-carbamimidoylanilino)methyl]-1-methylbenzimidazole-5-carbonyl]-pyridin-2-ylamino]propanoic acid
SDF	Download SDF
Canonical SMILES	CN1C2=C(C=C(C=C2)C(=O)N(CCC(=O)O)C3=CC=CC=N3)N=C1CNC4=CC=C(C=C4)C(=N)N
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Thrombin inhibition assay [1]:
Chromogenic assay	Human thrombin (0.042 U/mL) was pre-incubated for 10 mins at 37 °C with 10 different dilutions (concentration range of 0.003 ~ 100 μM) of BIBR 953 dissolved in DMSO or with DMSO as control. Upon addition of the pre-incubation mixture to the chromogenic substrate, tosyl-glycyl-prolyl-arginine-4-nitranilide acetate, nitraniline was cleaved by thrombin and the increase in absorbance at 405 nm, related to the free nitraniline, was measured in a spectrophotometer. By plotting the absorbance at 405 nm vs the concentration of the test compound, IC50 was calculated.
In intro experiment [2]:
Samples	Adult and neonatal platelet-poor plasma
Preparation method	The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.
Reacting condition	0, 40, 110, 180, 250 or 320 ng/mL
Applications	Without the presence of BIBR 953, neonatal and adult samples showed similar results on the time to clot initiation. In neonatal samples, BIBR 953 significantly delay clotting in a dose-dependent manner, with the difference increasing from 3 times for 40 ng/mL BIBR 953 to 9 times for 320 ng/mL BIBR 953.
Animal experiment [1]:
Animal models	Rats
Dosage form	i.v.
Applications	Compared with all of the inhibitors tested, BIBR 953 exhibited the strongest activity and the longest duration of action. Besides, it was well-tolerated in rats up to the highest dose of 10 mg/kg. However, BIBR 953 was not orally active because it was a very polar, a permanently charged molecule with a logP of -2.4 (n-octanol/buffer, pH 7.4).
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1]. Hauel NH, Nar H, Priepke H, Ries U, Stassen JM, Wienen W. Structure-based design of novel potent nonpeptide thrombin inhibitors. J Med Chem. 2002 Apr 25;45(9):1757-66. [2]. Nossair FF, Chan HHW, Gantioqui J, Atkinson HM, Berry LR, Chan AKC. In-vitro assessment of the effect of dabigatran on thrombosis of adult and neonatal plasma: comparisons using thromboelastography and microscopic visualization of fibrin clot structure. Blood Coagul Fibrinolysis. 2017 May 12.

Biological Activity

Description	BIBR 953 is a potent nonpeptide inhibitor of thrombin with IC50 value of 9.3 nM.
Targets	thrombin
IC50	9.3 nM

Quality Control

Purity = 99.44%

BIBR 953 (Dabigatran, Pradaxa) [211914-51-1]

Referencia A4077-100mg

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Marca : APExBIO Technology