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| Targets |
Pin1 inhibitor API-1 targets the peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1). Pin1 is a peptidyl-prolyl isomerase that catalyzes the cis-trans isomerization of proline residues in proteins, regulating protein conformation and function. API-1 targets the Pin1 peptidyl-prolyl isomerase domain and inhibits its cis-trans isomerizing activity with an IC50 of 72.3 nM.
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| ln Vitro |
SK-Hep-1, SNU-423, and Hep3B cell growth is strongly inhibited by the PIN1 inhibitor API-1, which has a low IC50 value (IC50=0.683-4.16 μM) [1].
Pin1 inhibitor API-1 demonstrates potent inhibition of Pin1 with an IC50 of 72.3 nM. It directly and specifically binds to the Pin1 peptidyl-prolyl isomerase (PPIase) domain. In cellular assays, it up-regulates miRNA biogenesis by retaining active XPO5 conformation. It suppresses hepatocellular carcinoma development. |
| ln Vivo |
By increasing the synthesis of mature miRNA, the PIN1 inhibitor API-1 suppresses the growth of mice tumors [1].
Pin1 inhibitor API-1 inhibits tumor growth by up-regulating mature miRNA biogenesis in mice. It suppresses the growth of mice tumors. It has shown promise in cancer research, highlighting its potential in therapeutic strategies targeting aberrant PIN1-mediated pathways involved in tumor growth and progression. |
| Enzyme Assay |
Pin1 PPIase activity assays are performed using recombinant Pin1 enzyme and a peptide substrate (e.g., Suc-Ala-Glu-Pro-Phe-pNA). The enzyme catalyzes the cis-trans isomerization of the peptide bond preceding proline. The reaction is monitored by measuring the change in absorbance at 390 nm as the trans isomer of the peptide is cleaved by chymotrypsin. API-1 is serially diluted and added to the reaction mixture. IC50 values are determined by non-linear regression analysis. Each concentration is tested in duplicate.
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| Cell Assay |
Cellular Pin1 inhibition is evaluated in cancer cell lines (e.g., hepatocellular carcinoma cells). Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with API-1 at various concentrations (0.1-10 µM) for 24-72 hours. Pin1 activity in cell lysates is measured using PPIase assays. miRNA biogenesis is assessed by qRT-PCR for mature miRNAs. XPO5 localization and conformation are assessed by immunofluorescence and Western blotting. Cell viability and proliferation are assessed using MTT or CellTiter-Glo assays. Each experiment includes vehicle controls.
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| Animal Protocol |
In vivo efficacy is evaluated in mouse xenograft models using hepatocellular carcinoma cells. API-1 is administered orally or intraperitoneally at doses determined by preclinical studies. Tumor growth is monitored by caliper measurements. At study endpoint, tumors are harvested for histopathological analysis and biochemical assays (Pin1 activity, miRNA levels, XPO5 conformation). Body weight and clinical signs are monitored throughout the study. Sample sizes typically range from 6-10 animals per group.
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| ADME/Pharmacokinetics |
Pin1 inhibitor API-1 has a molecular weight of 366.30 g/mol and a molecular formula of C15H13F3N6O2. Chemical name: N-[(4-{[(2-amino-7H-purin-6-yl)oxy]methyl}phenyl)methyl]-2,2,2-trifluoroacetamide. Purity: typically 98%. Solubility: DMSO. Storage: typically at -20°C. Bioavailability, half-life, and tissue distribution data are available from preclinical studies.
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| Toxicity/Toxicokinetics |
Limited toxicology data are available for Pin1 inhibitor API-1. As a Pin1 inhibitor, potential toxicities may include effects on cell cycle regulation and protein folding. Standard toxicology studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on rapidly dividing tissues. No clinical trials have been reported for this compound.
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| References |
[1]. Pu W, et al. Targeting Pin1 by inhibitor API-1 regulates microRNA biogenesis and suppresses hepatocellularcarcinoma development. Hepatology. 2018 Aug;68(2):547-560.
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| Additional Infomation |
Pin1 inhibitor API-1 is also known as API-1. It is a potent and specific inhibitor of Pin1 with an IC50 of 72.3 nM. It targets the Pin1 peptidyl-prolyl isomerase domain and inhibits its cis-trans isomerizing activity. It up-regulates miRNA biogenesis and suppresses hepatocellular carcinoma development. No clinical trials or regulatory approvals have been reported. The compound is for research use only.
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| Molecular Formula |
C15H13F3N6O2
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|---|---|
| Molecular Weight |
366.29792
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| Exact Mass |
366.105
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| CAS # |
680622-70-2
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| PubChem CID |
29987694
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| Appearance |
White to yellow solid powder
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| Melting Point |
208-211C
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| LogP |
2.463
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
487
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC=C1CNC(=O)C(F)(F)F)COC2=NC(=NC3=C2NC=N3)N
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| InChi Key |
AQFWAWXGBQPBIA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H13F3N6O2/c16-15(17,18)13(25)20-5-8-1-3-9(4-2-8)6-26-12-10-11(22-7-21-10)23-14(19)24-12/h1-4,7H,5-6H2,(H,20,25)(H3,19,21,22,23,24)
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| Chemical Name |
N-(4-(((2-Amino-9H-purin-6-yl)oxy)methyl)benzyl)-2,2,2-trifluoroacetamide
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| Synonyms |
Pin1 inhibitor API-1 Pin1 inhibitor API1 Pin1 inhibitor API 1
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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 : ~250 mg/mL (~682.50 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (5.92 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 21.7 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: ≥ 2.17 mg/mL (5.92 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 21.7 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: ≥ 2.17 mg/mL (5.92 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 | 2.7300 mL | 13.6500 mL | 27.3000 mL | |
| 5 mM | 0.5460 mL | 2.7300 mL | 5.4600 mL | |
| 10 mM | 0.2730 mL | 1.3650 mL | 2.7300 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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