SIAIS117
SIAIS117 is an ALK PROTAC degrader constructed based on Brigatinib (HY-12857) and VHL-1. SIAIS117 exhibits activity not only against wild-type ALK fusion proteins, but also effectively degrades the highly drug-resistant ALK G1202R mutant fusion protein. SIAIS117 significantly inhibits the proliferation of non-small cell lung cancer, small cell lung cancer, anaplastic large cell lymphoma, and drug-resistant cells expressing EML4-ALK G1202R. SIAIS117 can be used in relevant research on the above-mentioned malignant tumors.
(Pink: Anaplastic lymphoma kinase (ALK) Target protein ligand; Blue: VHL ligand (HY-125845); Black: linker (HY-W014125)).
For research use only. We do not sell to patients.
- CAS No.: 2353494-84-3
- Formula: C57H76ClN10O7PS
- Molecular Weight:1111.77
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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
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
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VHL |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| NCI-H2228 | IC50 |
46 nM
Compound: 18; SIAI5117
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Antiproliferative activity against human NCI-H2228 cells expressing EML4-ALK assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay
Antiproliferative activity against human NCI-H2228 cells expressing EML4-ALK assessed as reduction in cell viability incubated for 72 hrs by CCK8 assay
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[PMID: 32179332] |
| NCI-H69 | IC50 |
799 nM
Compound: 18; SIAI5117
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Antiproliferative activity against human NCI-H69 cells assessed as inhibition of cell proliferation
Antiproliferative activity against human NCI-H69 cells assessed as inhibition of cell proliferation
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[PMID: 32179332] |
| SR | IC50 |
1.7 nM
Compound: 18; SIAI5117
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Antiproliferative activity against human SR cells assessed as reduction in cell growth
Antiproliferative activity against human SR cells assessed as reduction in cell growth
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[PMID: 32179332] |
SIAIS117 (7-189 nM) effectively degrades wild-type and ALKG1202R mutant ALK fusion proteins in SR, H2228, and 293T cells with DC50 values of 7 nM, ~100 nM, and 189 nM, respectively, and does not degrade off-target Aurora A protein[1].
SIAIS117 (1.7-166 nM) potently inhibits proliferation of SR, H2228, and ALKG1202R mutant ALK-expressing cells with IC50 values of 1.7 nM, 46 nM, and 166 nM, respectively, and inhibits growth of SCLC cell lines at concentrations where brigatinib is ineffective[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NSCLC cell line H2228, Small cell lung cancer cell lines (NCI-H69, NCI-H1688)[1]
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Concentration:0-10 μM
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Incubation Time:72 h
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Result:Inhibited cell growth with an about two folds lower IC50 value (46 nM) comparing to SIAIS117NC (114 nM). Showed a good growth inhibition effect on NCI-H69 and NCI-H1688 cell line, with IC50 values of 799 and 259 nM, respectively.
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Cell Line:SR, H2228[1]
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Concentration:0, 1, 10, 50, 100, 500 nM
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Incubation Time:24 h
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Result:Inhibited all of the phosphorylation of ALK at 10 nM and inhibited pSTAT3 in SR cell, degraded ALK proteins at the concentration starting from 50 nM in H2228 cell, and significantly downregulated UCK2 and GAK. Caused sustained degradation of ALK protein in SR cells.
Chemical Information
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CAS No. 2353494-84-3
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Molecular Weight 1111.77
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Formula C57H76ClN10O7PS
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SMILES
COC(C=C1N(CC2)CCC2NC(CCCCCCCCCC(N[C@@H](C(C)(C)C)C(N3[C@@H](C[C@H](C3)O)C(NCC4=CC=C(C5=C(N=CS5)C)C=C4)=O)=O)=O)=O)=C(C=C1)NC6=NC=C(Cl)C(NC7=C(C=CC=C7)P(C)(C)=O)=N6
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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.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SIAIS117 Related Classifications
HY-146022 Related Classifications
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- SIAIS117
- 2353494-84-3
- SIAIS 117
- SIAIS-117
- PROTACs
- Anaplastic lymphoma kinase (ALK)
- small cell lung cancer cells
- ALK-positive anaplastic large cell lymphoma cells
- ALK TKI-resistant cells
- G1202R mutant ALK fusion proteins
- EML4-ALK
- Anaplastic lymphoma kinase
- VHL E3 ubiquitin ligase
- proteasomal degradation
- ALK ubiquitination
- non-small cell lung cancer cells
- Inhibitor
- inhibitor
- inhibit