SIAIS056
SIAIS056 is a BCR-ABL PROTAC degrader with a DC50 value of 0.18 nM. SIAIS056 time-dependently inhibits the BCR-ABL signaling pathway, accompanied by decreased phosphorylation of BCR-ABL and the downstream molecules STAT5 and CRKL in K562 cells. SIAIS056 induces the degradation of several clinically relevant resistance-conferring mutations of BCR-ABL. SIAIS056 exhibits anti-proliferative activity and induces substantial tumor regression in K562 xenograft models. SIAIS056 can be used for leukemia research.
(Pink: Bcr-Abl ligand (HY-175916); Blue: Cereblon ligand (HY-W586107); Black: linker (HY-41939)).
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- CAS No.: 2378581-37-2
- Formule: C35H34ClN9O5S2
- Masse moléculaire:760.28
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Activité biologique
Description
IC50 & Target
[1]|
Bcr-Abl 0.18 μM (DC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| K562 | IC50 |
0.49 nM
Compound: 17; SIAIS056
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Antiproliferative activity against human K562 cells assessed as cell growth inhibition measured after 48 hrs by CCK8 assay
Antiproliferative activity against human K562 cells assessed as cell growth inhibition measured after 48 hrs by CCK8 assay
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[PMID: 34217059] |
In Vitro
SIAIS056 (2 days) reduces anti-proliferative activity against K562 and 32D-BCR-ABL cells[1].
SIAIS056 (0-100 μM, 0-24 h) time-dependently inhibits the BCR-ABL signaling pathway, accompanied by decreased phosphorylation of BCR-ABL and its downstream molecules STAT5 and CRKL in K562 cells[1].
SIAIS056 (0-300 nM, 16 h) exerts the ability to overcome resistance to clinical tyrosine kinase inhibitors caused by (or associated with) the majority of clinically common BCR-ABL mutations in murine myeloid cell line 32D (including BCR-ABL-WT, BCR-ABL-G250E, BCR-ABL-E255V, BCR-ABL-V299L, BCR-ABL-F317L, BCR-ABL-F317V, BCR-ABL-T315A)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:K562 cells
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Concentration:0, 1, 3, 10, 30 and 100 nM
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Incubation Time:0, 2, 4, 8, 12, 18 and 24 h
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Result:Dramatically decreased the protein level of BCR-ABL and c-ABL at dose dependent manner (16 h) and time dependent manner (30 nM).
Induced the degradation of Src, but not PDGFRβ.
Dramatically decreased BCR-ABL after4h treatment at the 30 nM.
Time-Dependently inhibited the BCR-ABL signaling accompanied with decreased phosphorylation of BCR ABL and the downstream molecules STAT5 and CRKL.
Induced degradation of BCR-ABL and c-ABL at 30 nM for 8 h, which was significantly blocked by Pomalidomide (HY-10984) (4 μM, 2 h), Dasatinib (HY-10181) (100 nM, 2 h), MG132 (HY-13259) (2 μM, 2 h), Pevonedistat (HY-70062) (3 μM, 2 h).
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Cell Line:K562 cells
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Concentration:0, 10, 100 and 300 nM
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Incubation Time:16 h
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Result:Induced degradation of BCR-ABL mutations in BCR-ABL-WT, BCR-ABL-G250E, BCR-ABL-E255V, BCR-ABL-V299L, BCR-ABL-F317L, BCR-ABL-F317V and BCR-ABL-T315A, but in BCR-ABL-T3151 cells.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | MRT0-t | Vss | Vz | CL |
|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 2 mg/mL | i.v. | 4.23 h | 0.08 h | 1497.45 ng/mL | 926.29 ng·h/mL | 2 h | 5225.18 mL/kg | 13048.83 mL/kg | 2140.26 mL/h/kg |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:K562 cells (2 x 106) induced-NOD/SCID mouse[1]
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Dosage:1, 3 and 10 mg/kg
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Administration:i.p., once a day for 10 days
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Result:Observed a reduction in tumor burden at 1 mg/kg.
Induced complete tumor regression at 10 mg/kg, which was maintained even after drug withdrawal.
Showed tumor growth inhibition (TGI) values of 78.9%, 93.8%, and 98.8% for the 1, 3, and 10 mg/kg.
exhibited similar anti-leukemic activity at 3 mg/kg to that of Dasatinib (HY-10181) at 5 mg/kg (o.p.) (TGI: 93.8% versus 95.1%).
Showed well tolerate at the dose of 100 mg/kg.
Preserved the weight.
Showsed an anti-CML efficacy after 10 days.
Observed the BCR-ABL protein degradation at 4 day as well as suppression of BCR-ABL phosphorylation.
Chemical Information
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CAS No. 2378581-37-2
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Masse moléculaire 760.28
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Formule C35H34ClN9O5S2
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SMILES
O=C(C1=CN=C(NC2=CC(N3CCN(CC3)CCSC4=CC=CC(C(N5C6C(NC(CC6)=O)=O)=O)=C4C5=O)=NC(C)=N2)S1)NC7=C(C)C=CC=C7Cl
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Chen X, et al. Mighty mini-PROTACs: an emerging class of degraders. Eur J Med Chem. 2026 Jan 5;301:118202. [Content Brief]
[2]. Kang CH, et al. Induced protein degradation of anaplastic lymphoma kinase (ALK) by proteolysis targeting chimera (PROTAC). Biochem Biophys Res Commun. 2018 Oct 28;505(2):542-547. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SIAIS056 Related Classifications
HY-180969 Related Classifications
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