| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The targets include ALK (IC50 = 2.5 nM), ALK G1202R (IC50 = 6.6 nM), EGFR, FAK, PYK2, and PTK6. SIAIS-164018 is a heterobifunctional PROTAC that recruits an E3 ligase to these kinases, inducing their ubiquitination and proteasomal degradation, and blocks downstream signaling.
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|---|---|
| ln Vitro |
The proliferation of SR cells is considerably inhibited by SIAIS164018 (0–1 μM; 16 hours) [1]. Brigatinib was not as effective in inhibiting cell growth in ALK (G1202R)-overexpressing 293T and EGFR-expressing H1975 cell lines as SIAIS164018 (0-100 nM; 72 h) [1]. Significant G1 cell cycle arrest is induced in ALK-negative Calu-1 and MDA-MB-231 cells by SIAIS164018 (100 nM; 24 or 48 hours) [1]. In ALK-positive SR and ALK-negative Calu-1 cell lines, SIAIS164018 (0.01-1000 nM; 16h) down-regulates the protein levels of FAK, PYK2, FER, RSK1, and GAK [1].
SIAIS-164018 degrades ALK with IC50 = 2.5 nM and ALK G1202R with 6.6 nM, and promotes degradation of EGFR, FAK, PYK2, and PTK6. It inhibits cancer cell migration and invasion, causes G1 cell-cycle arrest, and induces apoptosis, with better properties than brigatinib in some assays. |
| ln Vivo |
No standard in vivo efficacy or pharmacokinetic data are publicly established for SIAIS-164018. Its development is primarily in vitro; in vivo evaluation would require formulation and dosing optimization, and compound-specific animal datasets are limited.
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| Enzyme Assay |
Kinase degradation is measured by treating cells with SIAIS-164018 and immunoblotting whole-cell lysates with antibodies against ALK, EGFR, FAK, PYK2, and PTK6; DC50 values are derived from dose-response curves. Ternary complex formation is confirmed by co-immunoprecipitation.
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| Cell Assay |
Cell proliferation experiment [1]
Cell Types: SR cell Tested Concentrations: 0-1 μM Incubation Duration: 16 h Experimental Results: Dramatically inhibited SR cell proliferation, with an IC50 value of 2 nM. Cell proliferation assay[1] Cell Types: 293T overexpressing ALK (G1202R) and H1975 cell line expressing EGFR Tested Concentrations: 0-100 nM Incubation Duration: 72 hrs (hours) Experimental Results: Brigatinib demonstrated better performance compared to ALK (G1202R) Inhibitory effects on cell proliferation - 293T-expressing and EGFR-expressing H1975 cell lines, with IC50s of 21 and 42 nM, respectively. Cell cycle analysis[1] Cell Types: ALK negative Calu-1 and MDA-MB-231 cells Tested Concentrations: 100 nM Incubation Duration: 24 or 48 hrs (hours) Experimental Results: Significant induction in ALK negative Calu-1 and MDA-MB-231 cells The G1 cell cycle arrest of MDA-MB-231 cells. Western Blot Analysis[1] Cell Types: SR and Calu-1 Cell Tested Concentrations: 0.01, 0.1, 1, 10, 100 and 1000 nM Incubation Duration: 16 hrs (hours) Experimental Results: Down-regulated the protein level of FAK, PYK2, FER, RSK1, and GAK. Cancer cells (e.g., ALK-dependent lines) are treated with SIAIS-164018; viability is measured by CellTiter-Glo, and kinase degradation, downstream phospho-signaling, cell-cycle distribution, and apoptosis are assessed by immunoblotting and flow cytometry. |
| Animal Protocol |
No standardized animal protocol is published. If evaluated, mice bearing ALK- or EGFR-dependent xenografts would receive SIAIS-164018 by intraperitoneal or oral route; tumor kinase levels and growth would be measured, but published in vivo datasets are insufficient.
|
| References |
| Molecular Formula |
C43H48CLN10O7P
|
|---|---|
| Molecular Weight |
883.330788612366
|
| Exact Mass |
882.313
|
| CAS # |
2353492-68-7
|
| Related CAS # |
SIAIS164018 hydrochloride
|
| PubChem CID |
141762856
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
4.6
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| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
62
|
| Complexity |
1690
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
COC1=C(C=CC(=C1)N2CCC(CC2)N3CCN(CC3)C(=O)CNC4=CC=CC5=C4C(=O)N(C5=O)C6CCC(=O)NC6=O)NC7=NC=C(C(=N7)NC8=CC=CC=C8P(=O)(C)C)Cl
|
| InChi Key |
AQGLXXCBEXDRNS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C43H48ClN10O7P/c1-61-34-23-27(11-12-30(34)48-43-46-24-29(44)39(50-43)47-31-8-4-5-10-35(31)62(2,3)60)51-17-15-26(16-18-51)52-19-21-53(22-20-52)37(56)25-45-32-9-6-7-28-38(32)42(59)54(41(28)58)33-13-14-36(55)49-40(33)57/h4-12,23-24,26,33,45H,13-22,25H2,1-3H3,(H,49,55,57)(H2,46,47,48,50)
|
| Chemical Name |
4-[[2-[4-[1-[4-[[5-chloro-4-(2-dimethylphosphorylanilino)pyrimidin-2-yl]amino]-3-methoxyphenyl]piperidin-4-yl]piperazin-1-yl]-2-oxoethyl]amino]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
|
| 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 : ~100 mg/mL (~113.21 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.83 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1321 mL | 5.6604 mL | 11.3208 mL | |
| 5 mM | 0.2264 mL | 1.1321 mL | 2.2642 mL | |
| 10 mM | 0.1132 mL | 0.5660 mL | 1.1321 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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