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Art. -Nr.: HY-146022

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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)).

Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.

CAS. Nr.: 2353494-84-3
Formel: C₅₇H₇₆ClN₁₀O₇PS
Molecular Weight:1111.77

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (269 KB)

SIAIS117 Chemical Structure

CAS. Nr.: 2353494-84-3

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

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^[1]. (Pink: Anaplastic lymphoma kinase (ALK) Target protein ligand; Blue: VHL ligand (HY-125845); Black: linker (HY-W014125)).

IC₅₀ & Target

VHL

Alle PROTACs Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
NCI-H2228	IC₅₀	46 nM Compound: 18; SIAI5117	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	[PMID: 32179332]
NCI-H69	IC₅₀	799 nM Compound: 18; SIAI5117	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	[PMID: 32179332]
SR	IC₅₀	1.7 nM Compound: 18; SIAI5117	Antiproliferative activity against human SR cells assessed as reduction in cell growth Antiproliferative activity against human SR cells assessed as reduction in cell growth	[PMID: 32179332]

In Vitro

SIAIS117 (7-189 nM) effectively degrades wild-type and ALK^G1202R 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 ALK^G1202R 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.

Cell Proliferation Assay

Cell Line:

NSCLC cell line H2228, Small cell lung cancer cell lines (NCI-H69, NCI-H1688)^[1]
Concentration:

0-10 μM
Incubation Time:

72 h
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.

Western Blot Analysis

Cell Line:

SR, H2228^[1]
Concentration:

0, 1, 10, 50, 100, 500 nM
Incubation Time:

24 h
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

CAS. Nr. 2353494-84-3
Molecular Weight 1111.77
Formel C₅₇H₇₆ClN₁₀O₇PS
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
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (269 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Song X, et al. Two novel strategies to overcome the resistance to ALK tyrosine kinase inhibitor drugs: Macrocyclic inhibitors and proteolysis-targeting chimeras. MedComm. 2021 Sep;2(3):341-350. [Content Brief]

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Bioz

Keywords

MOQ

Minimum order quantity

100 mg

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