| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Glycoprotein IIb/IIIa receptor (platelet integrin alphaIIbbeta3).
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| ln Vitro |
Sibrafiban inhibits ADP- and TRAP-stimulated fibrinogen binding and microaggregate formation in a concentration-dependent manner, while P-selectin expression remains largely unchanged. Decreased site occupancy from peak to trough by xilafiban does not result in increased platelet activation [3]. The effect of site occupancy by Sibrafiban on platelet activation was assessed using P-selectin expression, fibrinogen binding, and microaggregate formation.
Sibrafiban inhibits ADP- and TRAP-stimulated fibrinogen binding and microaggregate formation in a concentration-dependent manner, whereas P-selectin expression is relatively unaltered. It inhibits platelet aggregation with potent antiplatelet activity. The recovery of platelet aggregation may be slower after administration of sibrafiban with heparin and rt-PA. |
| ln Vivo |
The effects of Ro 44-3888 on ADP (17 μmol) platelet aggregation and skin bleeding time were investigated by oral administration of xilafiban 0.25 mg/kg/day or 0.5 mg/kg/day to 8 rhesus monkeys for 8 days. Maximal suppression of isolated platelet aggregation and extension of bleeding time by Ro 44-3888 is dose-dependent [1].
In beagles, sibrafiban (oral) resulted in >80% inhibition of ADP-mediated platelet aggregation and an approximate sixfold increase in bleeding time (BT) compared with baseline. In a Phase II clinical trial (TIMI 12), high levels of platelet inhibition were achieved in patients: mean peak values ranged from 47% to 97% inhibition of ADP-induced platelet aggregation on day 28 across doses. |
| Enzyme Assay |
Assay: In vitro binding to GP IIb/IIIa. Protocol: The prodrug sibrafiban is converted to the active form Ro 44-3888. The inhibition of fibrinogen binding to the GP IIb/IIIa receptor is measured using a standard competitive binding assay with labeled fibrinogen or specific small-molecule ligands. Alternatively, inhibition of platelet aggregation in platelet-rich plasma (PRP) is used to assess functional receptor blockade.
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| Cell Assay |
Cells: Human platelets. Protocol: Blood samples are collected into sodium citrate. Platelet-rich plasma (PRP) is prepared by centrifugation. PRP is pre-incubated with sibrafiban or its active metabolite for 5-10 minutes. Aggregation is induced by adding agonists such as ADP (5-20 microM) or TRAP. Aggregation is measured using a light transmission aggregometer over 5-10 minutes. Percent inhibition is calculated relative to vehicle control.
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| Animal Protocol |
Animal Model: Beagle dogs. Protocol: Beagles received oral sibrafiban alone or in combination with heparin, aspirin, and rt-PA. Blood samples were collected for up to 24 hours to measure plasma concentrations of sibrafiban and its metabolites. Platelet aggregation was measured ex vivo using PRP with ADP as an agonist. Bleeding time was measured from standard incisions. PD parameters (inhibition of aggregation, bleeding time prolongation) were derived.
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| ADME/Pharmacokinetics |
After oral administration to beagles, peak plasma concentrations of the intermediate prodrug Ro 48-3656 were observed earlier than the active antagonist Ro 44-3888 and were five- to sixfold higher. Co-administration with heparin/aspirin or heparin/rt-PA did not alter the PK of sibrafiban. In Phase I/II clinical trials, sibrafiban showed clear dose-dependent PK, with twice-daily dosing providing more sustained platelet inhibition than once-daily dosing.
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| Toxicity/Toxicokinetics |
In the TIMI 12 trial, major hemorrhage occurred in 1.5% of patients treated with sibrafiban and in 1.9% of patients treated with aspirin. Protocol-defined “minor” bleeding, usually mucocutaneous, occurred in 0% to 32% of patients in the various sibrafiban groups and in none of the patients treated with aspirin. Minor bleeding was related to total daily dose, once- versus twice-daily dosing, renal function, and presentation with unstable angina.
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| References | |
| Additional Infomation |
Acetic acid, ((1-((2S)-2-((4-((hydroxyamino)iminomethyl)benzoyl)amino)-1-oxopropyl)-4-piperidinyl)oxy)-, ethyl ester, is a small molecule drug. The International Nonproprietary Name (INN) prefix "-fiban" indicates that sibrafilban is a fibrinogen receptor antagonist (glycoprotein IIb/IIIa receptor antagonist). The monoisotopic molecular weight of sibrafilban is 420.2 Da.
A prodrug of Ro-44-3888; structure can be found in the first reference. Sibrafiban is an oral double prodrug that undergoes bioconversion first to the inactive prodrug Ro 48-3656 and then to the active GP IIb/IIIa antagonist Ro 44-3888. It was developed by Roche and advanced into Phase II clinical trials for acute coronary syndromes (e.g., TIMI 12). However, development was likely discontinued due to the modest efficacy and increased bleeding risk seen in clinical trials. |
| Molecular Formula |
C20H28N4O6
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|---|---|
| Molecular Weight |
420.45952
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| Exact Mass |
420.201
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| CAS # |
172927-65-0
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| PubChem CID |
9577986
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| Appearance |
White to off-white solid powder
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| Density |
1.33g/cm3
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| Index of Refraction |
1.598
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| LogP |
1.499
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
30
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| Complexity |
625
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCOC(=O)COC1CCN(CC1)C(=O)[C@H](C)NC(=O)C2=CC=C(C=C2)/C(=N/O)/N
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| InChi Key |
WBNUCLPUOSXSNJ-ZDUSSCGKSA-N
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| InChi Code |
InChI=1S/C20H28N4O6/c1-3-29-17(25)12-30-16-8-10-24(11-9-16)20(27)13(2)22-19(26)15-6-4-14(5-7-15)18(21)23-28/h4-7,13,16,28H,3,8-12H2,1-2H3,(H2,21,23)(H,22,26)/t13-/m0/s1
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| Chemical Name |
ethyl 2-[1-[(2S)-2-[[4-[(Z)-N'-hydroxycarbamimidoyl]benzoyl]amino]propanoyl]piperidin-4-yl]oxyacetate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~118.92 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3783 mL | 11.8917 mL | 23.7835 mL | |
| 5 mM | 0.4757 mL | 2.3783 mL | 4.7567 mL | |
| 10 mM | 0.2378 mL | 1.1892 mL | 2.3783 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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