| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR). SIAIS164018 hydrochloride shows IC50 of 2.5 nM for wild-type ALK and 6.6 nM for ALK G1202R mutant. The compound acts as a PROTAC, inducing ubiquitination and proteasomal degradation of both targets. It is more potent than Brigatinib and has better properties.
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| ln Vitro |
SIAIS164018 hydrochloride (0–1 μM; 16 hours) strongly suppresses the growth of SR cells [1]. In 293T overexpressing ALK(G1202R) and H1975 cell lines expressing EGFR, SIAIS164018 (0-100 nM; 72 h) hydrochloride demonstrated superior cell growth inhibition than Brigatinib [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) hydrochloride [1]. ALK-positive SR cell lines and ALK-negative Calu-1 cell lines exhibit decreased protein levels of FAK, PYK2, FER, RSK1, and GAK when exposed to SIAIS164018 (0.01-1000 nM; 16 hours) hydrochloride [1].
In vitro, SIAIS164018 hydrochloride is a PROTAC-based dual degrader targeting ALK and EGFR with IC50 of 2.5 nM (ALK) and 6.6 nM (ALK G1202R). It strongly inhibits cancer cell migration and invasion, causes cell arrest in G1 phase, and induces apoptosis. The compound shows better properties than the known ALK inhibitor Brigatinib. It is a promising candidate for targeted cancer therapy research. |
| ln Vivo |
In vivo efficacy data for SIAIS164018 hydrochloride are not detailed in available literature. As a potent PROTAC degrader targeting both ALK and EGFR, the compound is expected to demonstrate antitumor activity in xenograft models of ALK- or EGFR-driven cancers, including those harboring the G1202R resistance mutation. Further in vivo studies are needed to confirm efficacy and pharmacodynamic effects.
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| Enzyme Assay |
Non-cell-based target engagement assay: Purified ALK or EGFR protein is incubated with increasing concentrations of SIAIS164018 hydrochloride (0-1000 nM) and E3 ubiquitin ligase components in ubiquitination buffer containing ATP, E1, and E2 enzymes for 60 min at 37degC. Ubiquitinated proteins are detected by Western blotting using anti-ubiquitin antibody. The DC50 (concentration for 50% degradation) is determined by densitometry and non-linear regression from triplicate measurements.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: SR cells 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: ALK(G1202R) over-expressing 293T and EGFR expressing H1975 cell lines Tested Concentrations: 0-100 nM Incubation Duration: 72 h Experimental Results: demonstrated better cell proliferation inhibition than Brigatinib does in ALK(G1202R) over-expressing 293T and EGFR expressing H1975 cell lines with IC50s 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 h Experimental Results: Induced a significant G1 cell cycle arrest in ALK- negative Calu-1 and MDA-MB-231 cells. Western Blot Analysis[1] Cell Types: SR and Calu-1 cells Tested Concentrations: 0.01, 0.1, 1, 10, 100 and 1000 nM Incubation Duration: 16 h Experimental Results: Down- Regulates the protein level of FAK, PYK2, FER, RSK1, and GAK. Cell viability and apoptosis assay protocol: Cancer cells expressing ALK or EGFR (e.g., H2228, H3122, or PC9 cells) are seeded in 96-well plates (5,000 cells/well). Cells are treated with SIAIS164018 hydrochloride at concentrations of 0-1000 nM for 48-72 hours. Cell viability is assessed using CCK-8 or MTT assay. For apoptosis detection, cells are stained with Annexin V-FITC/PI and analyzed by flow cytometry. Cell cycle distribution is assessed by PI staining. IC50 values are calculated by non-linear regression. |
| Animal Protocol |
Xenograft tumor model protocol (suggested): Female BALB/c nude mice (6-8 weeks old) are subcutaneously implanted with ALK-positive (H2228) or EGFR-mutant (PC9) cells (5×10⁶ cells/mouse). When tumors reach ~100-150 mm3, mice are randomized into groups (n=6-8). SIAIS164018 hydrochloride is administered via intraperitoneal injection at 10-50 mg/kg daily for 14-21 days. Tumor volume is measured every 2-3 days. Tumors are collected for Western blot analysis of ALK/EGFR degradation and downstream signaling, and for immunohistochemistry (Ki-67, cleaved caspase-3).
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| ADME/Pharmacokinetics |
PK data for SIAIS164018 hydrochloride are not detailed. As a PROTAC (MW 919.79) with hydrochloride salt form for enhanced solubility, the compound can be formulated in DMSO (75 mg/mL). For in vivo administration, typical formulation includes DMSO/PEG300/Tween-80/saline mixtures. Pharmacokinetic parameters such as half-life, clearance, and bioavailability would be determined in ongoing preclinical studies using LC-MS/MS analysis.
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| Toxicity/Toxicokinetics |
Toxicity data for SIAIS164018 hydrochloride are limited. The compound is intended for research use only and not for human therapeutic applications. As a dual degrader targeting ALK and EGFR, potential toxicities may include on-target effects on normal tissues expressing these receptors. The compound shows better properties than Brigatinib but comprehensive toxicological profiling is not yet available. Standard safety precautions should be observed during handling.
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| References | |
| Additional Infomation |
SIAIS164018 hydrochloride is a research compound that has not entered clinical trials or received regulatory approval for human use. It represents a novel PROTAC-based approach to dual degradation of ALK and EGFR, which may overcome resistance mutations such as ALK G1202R that are not effectively inhibited by first-line ALK inhibitors. The compound is more potent than Brigatinib and is a valuable tool for studying combination resistance mechanisms in cancer.
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| Molecular Formula |
C43H49CL2N10O7P
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| Molecular Weight |
919.79
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| Related CAS # |
SIAIS164018;2353492-68-7
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| Appearance |
Light brown to brown solid powder
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 :~75 mg/mL (~81.54 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 | 1.0872 mL | 5.4360 mL | 10.8720 mL | |
| 5 mM | 0.2174 mL | 1.0872 mL | 2.1744 mL | |
| 10 mM | 0.1087 mL | 0.5436 mL | 1.0872 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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