SIAIS164018
SIAIS164018 is a multi-kinase (ALK, EGFR, FAK, PYK2, PTK6) PROTAC degrader, with IC50 values of 2.5 nM and 6.6 nM against ALK and ALK (G1202R), respectively. SIAIS164018 promotes the ubiquitination and degradation of ALK, EGFR, FAK, PYK2 and PTK6. SIAIS164018 induces cell cycle arrest at the G1 phase and triggers cell Apoptosis. SIAIS164018 exhibits preferential inhibitory activity against FER kinase. SIAIS164018 can be used in research related to non-small cell lung cancer, ovarian cancer and triple-negative breast cancer.
(Pink: Anaplastic lymphoma kinase (ALK) and EGFR and FAK and PYK2 and PTK6 ligand (HY-150910); Blue: Cereblon ligand (HY-14658); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 2353492-68-7
- Formula: C43H48ClN10O7P
- Molecular Weight:883.33
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[2]|
Cereblon |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK-293T | IC50 |
21 nM
Compound: 6; SIAIS164018
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Antiproliferative activity against human 293T cells overexpressing ALK G1202R mutant assessed as cell growth inhibition after 72 hrs
Antiproliferative activity against human 293T cells overexpressing ALK G1202R mutant assessed as cell growth inhibition after 72 hrs
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[PMID: 34138566] |
| NCI-H1975 | IC50 |
42 nM
Compound: 6; SIAIS164018
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Antiproliferative activity against human H1975 cells overexpressing EGFR L858R/T790M mutant assessed as cell growth inhibition after 72 hrs
Antiproliferative activity against human H1975 cells overexpressing EGFR L858R/T790M mutant assessed as cell growth inhibition after 72 hrs
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[PMID: 34138566] |
| SR | IC50 |
2 nM
Compound: 6; SIAIS164018
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Antiproliferative activity against human SR cells assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay
Antiproliferative activity against human SR cells assessed as inhibition of cell growth incubated for 72 hrs by CCK8 assay
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[PMID: 34138566] |
In Vitro
SIAIS164018 (0-1 μM; 16 h) significantly inhibits the proliferation of SR cells[2].
SIAIS164018 preferentially inhibits FER kinase activity over ALK kinase activity in cell-free KINOMEScan kinase profiling assays[3].
SIAIS164018 (0-100 nM; 72 h) exhibits better cell proliferation inhibitory activity than Brigatinib (HY-12857) in ALK (G1202R)-overexpressing 293T cells and EGFR-expressing H1975 cell lines[2].
SIAIS164018 (100 nM; 24-48 h) induces significant G1 cell cycle arrest in ALK-negative Calu-1 and MDA-MB-231 cells[2].
SIAIS164018 (<10 nM-100 nM) degrades ALK at concentrations of <10 nM and degrades EGFR at concentrations of 100 nM[4].
SIAIS164018 inhibits the proliferation of 293T cells overexpressing ALKG1202R, with an IC50 of 21 nM[4].
SIAIS164018 (0.01-1000 nM; 16 h) downregulates the protein levels of FAK, PYK2, FER, RSK1 and GAK in ALK-positive SR cell lines and ALK-negative Calu-1 cell lines[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:SR cells
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Concentration:0-1 μM
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Incubation Time:16 h
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Result:Significantly inhibited SR cell proliferation with an IC50 value of 2 nM.
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Cell Line:SR and Calu-1 cells
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Concentration:0.01, 0.1, 1, 10, 100 and 1000 nM
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Incubation Time:16 h
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Result:Down-regulated the protein level of FAK, PYK2, FER, RSK1, and GAK.
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Cell Line:ALK-negative Calu-1 and MDA-MB-231 cells
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Concentration:100 nM
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Incubation Time:24 h, 48 h
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Result:Induced a significant G1 cell cycle arrest in ALK-negative Calu-1 and MDA-MB-231 cells.
Parmacokinetics
| Species | Dose | Route | Bioavailability | T1/2 |
|---|---|---|---|---|
| Rat[2] | 10 mg/kg | p.o. | 18.4 % | 7.1 h |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 2353492-68-7
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Molecular Weight 883.33
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Formula C43H48ClN10O7P
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SMILES
O=C1NC(C(CC1)N2C(C3=C(C2=O)C(NCC(N4CCN(C5CCN(CC5)C6=CC=C(C(OC)=C6)NC7=NC=C(C(NC8=C(P(C)(C)=O)C=CC=C8)=N7)Cl)CC4)=O)=CC=C3)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (113.21 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (2.83 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocols
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Flow cytometric DNA-content cell-cycle staining
Flow cytometric DNA-content cell-cycle staining measures the fluorescence intensity of DNA-bound fluorochromes in single cells or nuclei to estimate DNA content distributions, allowing assignment of populations to G0/G1, S, and G2/M phases by DNA histogram deconvolution. Propidium iodide (PI) intercalates into DNA, and PI fluorescence is proportional to cellular DNA content when staining is performed under conditions that make DNA accessible and minimize non-DNA signal. Cells with G2/M DNA content are expected to show approximately twice the fluorescence intensity of G0/G1 cells, while S-phase cells occupy intermediate fluorescence values. PI-based DNA-content analysis can also detect cells with fractional DNA content, often reported as sub-G1, when DNA fragmentation and extraction during staining reduce retained DNA signal in apoptotic cells. DAPI is an alternative DNA fluorochrome for univariate DNA-content analysis, while bivariate approaches combining DNA content with proliferation
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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BrdU Incorporation Assay
Bromodeoxyuridine (BrdU) incorporation assay is based on the principle that BrdU, a thymidine analog, is incorporated into newly synthesized DNA during the S phase of the cell cycle, thereby serving as a marker of DNA replication and cellular proliferation. Incorporated BrdU can be detected using anti-BrdU antibodies following DNA denaturation, enabling visualization or quantification of proliferating cells through immunochemical detection methods such as immunofluorescence or immunohistochemistry.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Protocol for Cell Cycle
Cell-cycle analysis by flow cytometry measures DNA content in single cells to estimate the fraction of cells in G0/G1, S, and G2/M phases. Propidium iodide intercalates into DNA, and after RNA removal with RNase, fluorescence intensity reflects cellular DNA content: 2N cells are assigned to G0/G1, cells between 2N and 4N to S phase, and 4N cells to G2/M. DNA-content analysis alone cannot reliably separate G0 from G1 or G2 from M. Ki-67 can distinguish quiescent G0 cells from cycling cells, EdU or BrdU incorporation marks active DNA synthesis in S phase, and phospho-histone H3 staining identifies mitotic cells within the 4N population.
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
Purity & Documentation
References
[1]. Kossakowski K, et al. FDA-approved kinase inhibitors in PROTAC design, development and synthesis. Journal of enzyme inhibition and medicinal chemistry. 2025 Dec;40(1):2542357. [Content Brief]
[2]. Ren C, et al. Discovery of a Brigatinib Degrader SIAIS164018 with Destroying Metastasis-Related Oncoproteins and a Reshuffling Kinome Profile. Journal of medicinal chemistry. 2021 Jul 08;64(13):9152-9165. [Content Brief]
[3]. Zhang Y, et al. Development of the nonreceptor tyrosine kinase FER-targeting PROTACs as a potential strategy for antagonizing ovarian cancer cell motility and invasiveness. The Journal of biological chemistry. 2023 Jun;299(6):104825. [Content Brief]
[4]. Rallabandi NC, et al. EGFR molecular degraders: preclinical successes and the road ahead. Future Med Chem. 2025 Mar;17(6):633-636. [Content Brief]
Complete Stock Solution Preparation Table
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.1321 mL | 5.6604 mL | 11.3208 mL | 28.3020 mL |
| 5 mM | 0.2264 mL | 1.1321 mL | 2.2642 mL | 5.6604 mL | |
| 10 mM | 0.1132 mL | 0.5660 mL | 1.1321 mL | 2.8302 mL | |
| 15 mM | 0.0755 mL | 0.3774 mL | 0.7547 mL | 1.8868 mL | |
| 20 mM | 0.0566 mL | 0.2830 mL | 0.5660 mL | 1.4151 mL | |
| 25 mM | 0.0453 mL | 0.2264 mL | 0.4528 mL | 1.1321 mL | |
| 30 mM | 0.0377 mL | 0.1887 mL | 0.3774 mL | 0.9434 mL | |
| 40 mM | 0.0283 mL | 0.1415 mL | 0.2830 mL | 0.7075 mL | |
| 50 mM | 0.0226 mL | 0.1132 mL | 0.2264 mL | 0.5660 mL | |
| 60 mM | 0.0189 mL | 0.0943 mL | 0.1887 mL | 0.4717 mL | |
| 80 mM | 0.0142 mL | 0.0708 mL | 0.1415 mL | 0.3538 mL | |
| 100 mM | 0.0113 mL | 0.0566 mL | 0.1132 mL | 0.2830 mL |
SIAIS164018 Related Classifications
HY-147219 Related Classifications
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