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| 25mg |
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Purity: ≥98%
PCI-27483 is a novel, potent and reversible small-molecule inhibitor of activated factor VII (factor VIIa) with potential anticancer and antithrombotic activities. Factor VII is a serine protease which can be activated (FVIIa) upon binding with TF forming the FVIIa/TF complex, which induces intracellular signaling pathways by activating protease activated receptor 2 (PAR-2). Upon subcutaneous administration, factor VIIa inhibitor PCI-27483 selectively inhibits factor FVIIa in the VIIa/TF complex, which may prevent PAR-2 activation and PAR2-mediated signal transduction pathways, thereby inhibiting tumor cell proliferation, angiogenesis, and metastasis of TF-overexpressing tumor cells.
| Targets |
FVIIa/TF complex (factor VIIa/tissue factor complex) with high potency and selectivity. [2]
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|---|---|
| ln Vitro |
In BxPC3 cells, a human pancreatic adenocarcinoma cell line that expresses TF extensively, PCI-27483 suppresses TF:FVIIa complex-induced ERK1/2 phosphorylation and the consequent activation of c-fos. Furthermore, PCI-27483 has the ability to inhibit TF:FVIIa-induced IL8 secretion in MDA-MB-231 and BxPC3 breast cancer cells [2].
Preclinical studies showed antitumor effects of PCI-27483. [2] |
| ln Vivo |
PCI-27483 showed dose-dependent reduction of fibrin buildup, PT, and thrombosis. PCI-27483 (4 mg/kg) has an anticoagulant effect comparable to enoxaparin (2 mg/kg) [1]. When BxPC3 cells are implanted into CD1 nu/nu mice, PCI-27483 (0 and 90 mg/kg, subcutaneously) suppresses the formation of tumors [2].
In a baboon model of arterial thrombosis, PCI-27483 showed dose-dependent inhibition of thrombus formation, fibrin accumulation, and prolongation of prothrombin time (PT). PCI-27483 at 4 mg/kg showed comparable anticoagulation effects to enoxaparin 2 mg/kg. [2] |
| Animal Protocol |
A baboon model of arterial thrombosis was used to evaluate the antithrombotic effects of PCI-27483. The drug was administered intravenously, and thrombus formation, fibrin accumulation, and PT were measured. [2]
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| ADME/Pharmacokinetics |
In a phase I study of healthy volunteers, the half-life of PCI-27483 was 10–12 hours after a single subcutaneous injection. The international normalized ratio (INR) was closely related to plasma drug concentration. [2]
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| Toxicity/Toxicokinetics |
PCI-27483 was well tolerated in healthy volunteers. [2]
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| References | |
| Additional Infomation |
PCI-27483 has been used in research for the treatment of pancreatic cancer, ductal adrenal carcinoma, and exocrine pancreatic cancer. PCI-27483, a factor VIIa inhibitor, is a reversible small-molecule inhibitor of factor VII (factor VIIa) with potential antitumor and antithrombotic activities. Factor VII is a serine protease that is activated upon binding to tissue factor (TF) to form the FVIIa/TF complex (FVIIa). This complex induces intracellular signaling pathways by activating protease-activated receptor 2 (PAR-2). After subcutaneous injection, the factor VIIa inhibitor PCI-27483 selectively inhibits factor FVIIa in the VIIa/TF complex, potentially preventing PAR-2 activation and PAR2-mediated signal transduction pathways, thereby inhibiting the proliferation, angiogenesis, and metastasis of TF-overexpressing tumor cells. Furthermore, this drug can inhibit extrinsic and intrinsic coagulation cascades, thereby preventing thrombosis. Tissue factor (TF) is a blood protein overexpressed on the surface of various tumor cells and may be associated with poor prognosis; PAR-2 (also known as thrombin receptor-like protein 1) is a G protein-coupled receptor (GPCR) and protease-activated receptor. PCI-27483 is a small molecule with an undisclosed structure that is being developed as a factor VIIa/tissue factor inhibitor. It is currently being evaluated in a phase Ib/II clinical trial in patients with pancreatic cancer treated with gemcitabine. [2]
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| Molecular Formula |
C26H24N6O9S
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|---|---|
| Molecular Weight |
596.568564414978
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| Exact Mass |
596.132
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| CAS # |
871266-63-6
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| PubChem CID |
135425273
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.7±0.1 g/cm3
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| Index of Refraction |
1.775
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| LogP |
-0.74
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| Hydrogen Bond Donor Count |
9
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
42
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| Complexity |
1150
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| Defined Atom Stereocenter Count |
1
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| SMILES |
OC1C(C2C(O)=CC=C(S(=O)(=O)N)C=2)=CC(CC(=O)N[C@H](C(=O)O)CC(=O)O)=CC=1C1=NC2C=CC(=CC=2N1)C(N)=N
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| InChi Key |
WDJHHCAKBRKCLW-IBGZPJMESA-N
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| InChi Code |
InChI=1S/C26H24N6O9S/c27-24(28)12-1-3-17-18(8-12)32-25(31-17)16-6-11(7-21(34)30-19(26(38)39)10-22(35)36)5-15(23(16)37)14-9-13(42(29,40)41)2-4-20(14)33/h1-6,8-9,19,33,37H,7,10H2,(H3,27,28)(H,30,34)(H,31,32)(H,35,36)(H,38,39)(H2,29,40,41)/t19-/m0/s1
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| Chemical Name |
(S)-2-(2-(5-(5-carbamimidoyl-1H-benzo[d]imidazol-2-yl)-2',6-dihydroxy-5'-sulfamoyl-[1,1'-biphenyl]-3-yl)acetamido)succinic acid.
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| Synonyms |
PCI27483; PCI-27483; PCI 27483.
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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 : ~62.5 mg/mL (~104.77 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.49 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 20.8 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 (3.49 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 (3.49 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 | 1.6762 mL | 8.3812 mL | 16.7625 mL | |
| 5 mM | 0.3352 mL | 1.6762 mL | 3.3525 mL | |
| 10 mM | 0.1676 mL | 0.8381 mL | 1.6762 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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