| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
|
| Targets |
Cereblon
|
|---|---|
| ln Vitro |
PROTAC-O4I2 preferentially degrades SF3B1 and prevents the formation of tumors in cells by introducing thalidomide into the ubiquitin E3 ligase cereblon (CRBN) [1]. STAT-O4I2 inhibits and degrades SF3B1 in K562 cells. SF3B1 WT, SF3B1 OE, and SF3B1 K700E cells are non-proliferatively affected by PROTAC-O4I2, with IC50 values of 228, 63, and 90 nM, respectively [1]. With an IC50 value of 0.244 μM in K562 cells, PROTAC-O4I2 causes FLAG-SF3B1 degradation in a concentration-dependent manner [1].
|
| ln Vivo |
PROTAC-O4I2 (10 μM) inhibits the maintenance and development of the tumor, hence considerably increasing the survival rate of Drosophila in the intestinal tumor model [1].
|
| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: K562 control cells (WT), cells overexpressing SF3B1 (OE), and cells expressing SF3B1K700E (K700E) Tested Concentrations: 1 pM, 0.1 nM, 10 nM, 1 μM, 100 μM Incubation Duration: 72 hrs (hours) Experimental Results: In K562 WT cells, the parental compound O4I2 demonstrated a marginal anti-proliferation effect (IC50 >10 μM). In In contrast, PROTAC-O4I2 demonstrated Dramatically higher toxicity with an IC50 of 228 nM, nearly 3-fold less potent than pladienolide B (IC50, 76 nM). Cells overexpressing SF3B1 WT was slightly resistant to pladienolide B (IC50, 134 nM), but more sensitive to PROTAC-O4I2 (an IC50 value of 63 nM). Apoptosis Analysis[1] Cell Types: K562 cell Tested Concentrations: 1 μM Incubation Duration: 48 h Experimental Results: Induced cellular apoptosis s in cells expressing SF3B1WT or SF3B1K700E. |
| Animal Protocol |
Animal/Disease Models: Drosophila melanogaster[1]
Doses: 10 μM Route of Administration: Flies were fed on a round filter paper loaded with PROTAC-O4I2 in a 5% sucrose solution , maintained at 18℃ and flipped into a freshly prepared vial every 2 days. Experimental Results: diminished stem cell activity, blocked the initiation and growth of tumor, and improved the survival of the Drosophila ISC tumor model. |
| References |
| Molecular Formula |
C29H29CLN6O5S
|
|---|---|
| Molecular Weight |
609.10
|
| Exact Mass |
608.16
|
| CAS # |
2785323-62-6
|
| PubChem CID |
162641046
|
| Appearance |
White to yellow solid powder
|
| Density |
1.453±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)
|
| LogP |
4.9
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
42
|
| Complexity |
1030
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1C=CC(=CC=1)NC1=NC(=CS1)C(NCCCCCCNC1=CC=CC2C(N(C(C=21)=O)C1C(NC(CC1)=O)=O)=O)=O
|
| InChi Key |
UWYLVQJEOCYCEW-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C29H29ClN6O5S/c30-17-8-10-18(11-9-17)33-29-34-21(16-42-29)25(38)32-15-4-2-1-3-14-31-20-7-5-6-19-24(20)28(41)36(27(19)40)22-12-13-23(37)35-26(22)39/h5-11,16,22,31H,1-4,12-15H2,(H,32,38)(H,33,34)(H,35,37,39)
|
| Chemical Name |
2-(4-chloroanilino)-N-[6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]hexyl]-1,3-thiazole-4-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : 250 mg/mL (410.44 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.41 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6418 mL | 8.2088 mL | 16.4177 mL | |
| 5 mM | 0.3284 mL | 1.6418 mL | 3.2835 mL | |
| 10 mM | 0.1642 mL | 0.8209 mL | 1.6418 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
