| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
FGFR3-TACC3[1]
FGFR3-TACC3 fusion protein. SNIPER(TACC3)-11 binds to TACC3 and recruits an E3 ubiquitin ligase via the IAP ligand, leading to ubiquitination and proteasomal degradation of the oncogenic FGFR3-TACC3 protein. |
|---|---|
| ln Vitro |
Compound 5a (0.3-3 μM; 6 hours) of SNIPER(TACC3)-11 lowers FGFR3-TACC3 levels[1]. At 3 µM, SNIPER(TACC3)-11 (0.3-3 μM; 72 hours) suppresses the growth of RT4 cells but not HeLa cells[1].
SNIPER(TACC3)-11 (0.3-3 uM; 6 h) reduces FGFR3-TACC3 protein levels in treated cells. At 3 uM (72 h), it suppresses the growth of RT4 bladder cancer cells, which are positive for FGFR3-TACC3, while having no effect on HeLa cells. It is a novel degrader for this oncogenic fusion. |
| ln Vivo |
SNIPER(TACC3)-11 potently reduces FGFR3-TACC3 protein levels and suppresses the growth of FGFR3-TACC3-positive cancer cells in vitro. In vivo efficacy has not been detailed, but as a PROTAC, it is expected to reduce fusion protein levels in tumor tissues, potentially leading to tumor growth inhibition in xenograft models.
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| Enzyme Assay |
Cell-free binding assays are not applicable as SNIPER(TACC3)-11 is a PROTAC. Its ability to bind to both TACC3 and the E3 ligase can be assessed using surface plasmon resonance (SPR) or TR-FRET. The ternary complex formation between the compound, TACC3, and the E3 ligase can be measured using an AlphaLISA assay.
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| Cell Assay |
RT4 bladder cancer cells (FGFR3-TACC3-positive) are seeded in 96-well plates and treated with SNIPER(TACC3)-11 at 0.3-3 microM for 6-72 hours. FGFR3-TACC3 protein levels are quantified by Western blot using an anti-FGFR3 antibody. Cell proliferation is assessed by MTT or CellTiter-Glo assay after 72 hours of treatment. HeLa cells serve as a negative control.
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| Animal Protocol |
For in vivo studies, SNIPER(TACC3)-11 would be administered via intraperitoneal injection to mice bearing RT4 xenograft tumors. Dosing regimens are not specified but typically range from 20-50 mg/kg. Tumor volumes are measured with calipers. At termination, tumors are excised for Western blot analysis to confirm FGFR3-TACC3 degradation.
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| ADME/Pharmacokinetics |
No specific PK data are reported for SNIPER(TACC3)-11. The molecular weight is 995.26 (C51H66N10O7S2). The compound is a PROTAC with a high molecular weight, which may affect oral bioavailability. It is typically administered by intraperitoneal injection for in vivo studies. Solubility: DMSO (10-50 mg/mL).
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported. As a degrader of FGFR3-TACC3, a fusion protein primarily expressed in cancer cells, on-target toxicity may be limited. The IAP ligand component could potentially affect normal cell apoptosis. Comprehensive toxicological assessments have not been published.
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| References | |
| Additional Infomation |
Other information: SNIPER(TACC3)-11 (CAS 2906151-68-4) is a research compound and not FDA-approved. It is a potent degrader of the FGFR3-TACC3 oncogenic fusion protein, with degradation observed at 0.3-3 uM. It is a valuable tool for studying the function of FGFR3-TACC3 in bladder cancer and other fusion-driven cancers. For research use only.
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| Molecular Formula |
C51H66N10O7S2
|
|---|---|
| Molecular Weight |
995.262548923492
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| Exact Mass |
994.455
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| CAS # |
2906151-68-4
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| PubChem CID |
163322326
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| Appearance |
White to off-white solid powder
|
| LogP |
7.4
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| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
16
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| Rotatable Bond Count |
26
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| Heavy Atom Count |
70
|
| Complexity |
1610
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| Defined Atom Stereocenter Count |
3
|
| SMILES |
C[C@@H](C(=O)N[C@@H](C1CCCCC1)C(=O)N2CCC[C@H]2C3=NC(=CS3)C(=O)C4=CC(=CC=C4)OCCOCCOCCNC(=O)C5=CC=C(C=C5)C6=NC(=CS6)CNC7=NC=CC(=N7)NCC(C)C)NC
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| InChi Key |
CTMIQTSKAZXRFZ-YSQZVTEJSA-N
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| InChi Code |
InChI=1S/C51H66N10O7S2/c1-33(2)29-55-43-19-20-54-51(59-43)56-30-39-31-69-48(57-39)37-17-15-36(16-18-37)47(64)53-21-23-66-24-25-67-26-27-68-40-13-8-12-38(28-40)45(62)41-32-70-49(58-41)42-14-9-22-61(42)50(65)44(35-10-6-5-7-11-35)60-46(63)34(3)52-4/h8,12-13,15-20,28,31-35,42,44,52H,5-7,9-11,14,21-27,29-30H2,1-4H3,(H,53,64)(H,60,63)(H2,54,55,56,59)/t34-,42-,44-/m0/s1
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| Chemical Name |
N-[2-[2-[2-[3-[2-[(2S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]pyrrolidin-2-yl]-1,3-thiazole-4-carbonyl]phenoxy]ethoxy]ethoxy]ethyl]-4-[4-[[[4-(2-methylpropylamino)pyrimidin-2-yl]amino]methyl]-1,3-thiazol-2-yl]benzamide
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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: 100 mg/mL (100.48 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0048 mL | 5.0238 mL | 10.0476 mL | |
| 5 mM | 0.2010 mL | 1.0048 mL | 2.0095 mL | |
| 10 mM | 0.1005 mL | 0.5024 mL | 1.0048 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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