| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
PHT-7.3 targets the CNK1 PH domain, a protein interaction module that binds to phosphoinositides and mediates membrane localization of CNK1. By inhibiting the PH domain, the compound disrupts CNK1-mediated Ras signaling, which plays a role in cell proliferation and survival. The compound exhibits a Kd of 4.7 µM for the CNK1 PH domain.
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| ln Vitro |
In vitro, PHT-7.3 selectively inhibits the CNK1 PH domain with a Kd of 4.7 µM. By disrupting CNK1-mediated Ras signaling, the compound modulates downstream signaling pathways involved in cell proliferation. The compound has demonstrated antitumor activity in preclinical studies.
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| ln Vivo |
Mut-KRas(G12S) A549 xenografts and mut-KRasG12V H441 xenografts show cytostatic antitumor activity in response to PHT-7.3 (200 mg/kg; i.p.; daily; for 20 days) [1].
In vivo, PHT-7.3 has antitumor activity. As a CNK1 PH domain inhibitor, it has the potential to inhibit tumor growth by disrupting Ras signaling. Preclinical studies are expected to demonstrate its efficacy in tumor models. |
| Enzyme Assay |
In vitro binding assays for CNK1 PH domain inhibition typically involve fluorescence polarization or surface plasmon resonance to measure the binding of PHT-7.3 to recombinant CNK1 PH domain protein. The compound is incubated with the PH domain at varying concentrations, and the binding affinity (Kd) is calculated from the binding curves.
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| Cell Assay |
In vitro cellular assays are performed using cancer cell lines with activated Ras signaling. Cells are treated with PHT-7.3 at various concentrations for 48-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Ras signaling inhibition is confirmed by Western blot analysis of phospho-ERK and other downstream markers.
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| Animal Protocol |
Animal/Disease Models: Female NOD-SCID (severe combined immunodeficient) mouse (mut-KRas A549 NSCLC xenograft, mut-KRas H441 NSCLC xenograft) [1]
Doses: 200 mg/kg Route of Administration: intraperitoneal (ip) injection, daily, for 20 days Experimental Results: In mut-KRas(G12S) A549 xenografts and mut-KRasG12V H441 xenografts. In vivo studies are conducted in tumor-bearing mouse models. PHT-7.3 is administered at various doses. Tumor volume is measured periodically, and tumors are harvested for biomarker analysis, including assessment of proliferation and apoptosis markers. |
| ADME/Pharmacokinetics |
PHT-7.3 (molecular weight 433.52, formula C₂₄H₂₃N₃O₃S) is a small-molecule compound. It is soluble in DMSO and is typically stored at -20°C. Its physicochemical properties support its use in both in vitro and in vivo studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of PHT-7.3 have been limited, as the compound is primarily used as a research tool. No significant toxicity has been reported in the available literature. The compound's safety profile supports its use for studying CNK1 PH domain function and Ras signaling.
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| References | |
| Additional Infomation |
PHT-7.3 is a selective inhibitor of the CNK1 PH domain with antitumor activity. Its mechanism involves disrupting CNK1-mediated Ras signaling by binding to the PH domain. The compound is primarily used for research purposes and has not received regulatory approval for clinical use. It serves as a valuable tool for studying the role of CNK1 in Ras signaling and cancer.
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| Molecular Formula |
C24H23N3O3S
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|---|---|
| Molecular Weight |
433.52272439003
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| Exact Mass |
433.146
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| CAS # |
1614225-93-2
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| PubChem CID |
76287542
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
661
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C=C(C2C=CC(C)=CC=2)N=C1CN1C(C2C=CC=CC=2C(CC2OCCCO2)=N1)=O
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| InChi Key |
AFPMVLVIYVAFSP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H23N3O3S/c1-16-7-9-17(10-8-16)21-15-31-22(25-21)14-27-24(28)19-6-3-2-5-18(19)20(26-27)13-23-29-11-4-12-30-23/h2-3,5-10,15,23H,4,11-14H2,1H3
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| Chemical Name |
4-(1,3-dioxan-2-ylmethyl)-2-[[4-(4-methylphenyl)-1,3-thiazol-2-yl]methyl]phthalazin-1-one
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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 (~144.17 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (14.42 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 62.5 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: ≥ 6.25 mg/mL (14.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3067 mL | 11.5335 mL | 23.0670 mL | |
| 5 mM | 0.4613 mL | 2.3067 mL | 4.6134 mL | |
| 10 mM | 0.2307 mL | 1.1533 mL | 2.3067 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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