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Purity: ≥98%
TPI-1 (full name: Tyrosine Phosphatase Inhibitor 1) is an inhibitor of SHP-1 (Src homology region 2 domain-containing phosphatase 1) with an IC50 of 40 nM. It was identified from a library of 34,000 drug-like compounds with anticancer activities. TPI-1 selectively increased SHP-1 phospho-substrates (pLck-pY394, pZap70, and pSlp76) in Jurkat T cells but had little effects on pERK1/2 or pLck-pY505 regulated by phosphatases SHP-2 or CD45, respectively. Significantly, TPI-1 inhibited (approximately 83%) the growth of B16 melanoma tumors in mice at a tolerated oral dose in a T cell-dependent manner but had little effects on B16 cell growth in culture. TPI-1 also inhibited B16 tumor growth and prolonged tumor mice survival as a tolerated s.c. agent. TPI-1 analogs were identified with improved activities in IFN-gamma(+) cell induction and in anti-tumor actions. These results designate TPI-1 as a novel SHP-1 inhibitors with anti-tumor activity likely via an immune mechanism, supporting SHP-1 as a novel target for cancer treatment.
| ln Vitro |
One possible therapeutic target for cancer has been identified as SHP-1. As the SHP-1 phosphate substrate pLck-pY394 is increased, TPI-1 becomes effective at 10 ng/mL. TPI-1 has a slight impact on pERK1/2 and pLck-pY505, but it preferentially increases SHP-1 phosphosubstrates (pLck-pY394, pZap70, and pSlp76) in Jurkat T cells. TPI-1 stimulates IFNγ+ cells in human peripheral blood and mouse spleen [1].
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| ln Vivo |
TPI-1 has no effect on B16 cell proliferation in culture, but at a tolerable oral dosage it reduces the formation of B16 melanoma tumors in mice in a T cell-dependent way. As a result, TPI-1 also raises IFNγ+ and pLck-pY394 in mice. As a well-tolerated SC drug, TPI-1 also prevents the formation of B16 tumors and extends the longevity of tumor mice[1].
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| References |
| Molecular Formula |
C₁₂H₆CL₂O₂
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| Molecular Weight |
253.08
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| Exact Mass |
251.974
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| CAS # |
79756-69-7
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| Related CAS # |
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| PubChem CID |
948589
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| Appearance |
White to yellow solid powder
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| LogP |
3.084
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
16
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| Complexity |
385
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ZKHFYORNAYYOTM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H6Cl2O2/c13-7-1-3-11(14)9(5-7)10-6-8(15)2-4-12(10)16/h1-6H
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| Chemical Name |
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.88 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: ≥ 2.5 mg/mL (9.88 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 25.0 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: ≥ 2.5 mg/mL (9.88 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 | 3.9513 mL | 19.7566 mL | 39.5132 mL | |
| 5 mM | 0.7903 mL | 3.9513 mL | 7.9026 mL | |
| 10 mM | 0.3951 mL | 1.9757 mL | 3.9513 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.
TPI-1 inhibits recombinant and cellular SHP-1 and had little cytotoxicity in vitro and in mice.J Immunol.2010 Jun 1;184(11):6529-36. |
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TPI-1 selectively increases SHP-1 phospho-substrates in Jurkat cells at low nM levels.J Immunol.2010 Jun 1;184(11):6529-36. |
 TPI-1 inhibits B16 tumor growth as a tolerated single agent.J Immunol.2010 Jun 1;184(11):6529-36. |
 TPI-1 induces IFNγ+cells in mouse splenocytes and human peripheral bloodin vitro.
TPI-1 increases spleen pLck-pY394 and IFNγ+cells in mice. |
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 TPI-1 analogs TPI-1a2 and TPI-1a4 have anti-tumors in mice at tolerated oral doses.J Immunol.2010 Jun 1;184(11):6529-36. |
 TPI-1 analogs inhibit rSHP-1 in correlation with activity to increase SHP-1 phospho-substrate pLck-pY394 in Jurkat cells and induce IFNγ+ cells in mouse splenocytes. |
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