| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
PDE6D CK1α IKZF1 IKZF3
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|---|---|
| ln Vitro |
In MOLT4 cells, FPFT-2216 (1 μM; 5 hours) not only destroys its known targets, IKZF1, IKZF3, and CK1α, but also PDE6D [1]. PDE6D completely degrades in 2 hours with FPFT-2216 (1 μM; 0 h, 2 h, 4 h, 6 h, 16 h, 24 h), and it continues to degrade in MOLT4 cells for at least 24 hours [1]. PDE6D is more than 50% degraded in FPFT-2216 at a dose of 8 nM, with maximum degradation in MOLT4 cells at 200 nM (0 nM, 1.6 nM, 8 nM, 40 nM, 200 nM, 1 μM; 4 hours). Dosage breaks down PDE6D, IKZF1, IKZF3, and CK1α[1]. The proliferation of MIA PaCa-2 cells that are dependent on KRASG12C is not inhibited by FPFT-2216 [1]. While FPFT-2216 (10, 20, 40 μM; 14 or 24 hours) significantly upregulates IL-2, in naive CD4+ T cells it is less efficacious than Pomalidomide [2]. The immunomodulatory drugs (IMiD) ubiquitin-proteasome degradation substrates IKZF1 and CK-1α are degraded by FPFT-2216 (10 μM; 14 or 24 hours) in naive CD4+ T cells [2].
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| ln Vivo |
In CRBNI391V mice, FPFT-2216 (30 mg/kg; po or ip) significantly degrades CK-1α and IKZF1 [2].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: MOLT4 cells Tested Concentrations: 1 μM Incubation Duration: 0 h, 2 h, 4 h, 6 h, 16 h, 24 h Experimental Results: demonstrated complete degradation of PDE6D within 2 h, and the degradation of PDE6D persisted for at least 24 h. Western Blot Analysis[1] Cell Types: MOLT4 cells Tested Concentrations: 0 nM, 1.6 nM, 8 nM, 40 nM, 200 nM, 1 μM Incubation Duration: 4 h Experimental Results: demonstrated over 50% degradation of PDE6D at a dose of 8 nM, while maximum degradation of PDE6D along with IKZF1, IKZF3, and CK1α at a dose of 200 nM. |
| Animal Protocol |
Animal/Disease Models: CRBNI391V mice[2]
Doses: 30 mg/kg (solubilized in 0.5% carboxymethylcellulose/sodium and 0.25% Tween 80) Route of Administration: po or ip Experimental Results: Induced significant degradation of CK-1α, and IKZF1. |
| References |
[1]. Teng M, et al. Development of PDE6D and CK1α Degraders through Chemical Derivatization of FPFT-2216. J Med Chem. 2022 Jan 13;65(1):747-756.
[2]. Gemechu Y, et al. Humanized cereblon mice revealed two distinct therapeutic pathways of immunomodulatory drugs. Proc Natl Acad Sci U S A. 2018;115(46):11802-11807. |
| Molecular Formula |
C12H12N4O3S
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|---|---|
| Molecular Weight |
292.31
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| CAS # |
2367619-87-0
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| SMILES |
N1C(=O)CCC(N2C=C(C3C(OC)=CSC=3)N=N2)C1=O
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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 : 100 mg/mL (342.10 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.55 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 (8.55 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 saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 2.5 mg/mL (8.55 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4210 mL | 17.1051 mL | 34.2103 mL | |
| 5 mM | 0.6842 mL | 3.4210 mL | 6.8421 mL | |
| 10 mM | 0.3421 mL | 1.7105 mL | 3.4210 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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