2. PROTAC Protein Tyrosine Kinase/RTK
  3. PROTACs Bcr-Abl
  4. 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)).

For research use only. We do not sell to patients.

SIAIS056

SIAIS056 Chemical Structure

CAS No. : 2378581-37-2

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SIAIS056 Related Antibodies

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Description

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[1][2]. (Pink: Bcr-Abl ligand (HY-175916); Blue: Cereblon ligand (HY-W586107); Black: linker (HY-41939)).

IC50 & Target[1]

Bcr-Abl

0.18 μM (DC50)

Cellular Effect
Cell Line Type Value Description References
K562 IC50
0.49 nM
Compound: 17; SIAIS056
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
[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.

SIAIS056 Related Antibodies

Western Blot Analysis[1]

Cell Line: K562 cells
Concentration: 0, 1, 3, 10, 30 and 100 nM
Incubation Time: 0, 2, 4, 8, 12, 18 and 24 h
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).

Western Blot Analysis[1]

Cell Line: K562 cells
Concentration: 0, 10, 100 and 300 nM
Incubation Time: 16 h
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

SIAIS056 (1-10 mg/kg, i.p., once a day for 10 days) induces effective degradation of BCR-ABL protein and substantial anti-leukemic activity in a murine xenograft mouse model of K562 cells[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: K562 cells (2 x 106) induced-NOD/SCID mouse[1]
Dosage: 1, 3 and 10 mg/kg
Administration: i.p., once a day for 10 days
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.
Molecular Weight

760.28

Formula

C35H34ClN9O5S2
CAS No.
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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SIAIS056 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

SIAIS0562378581-37-2SIAIS 056SIAIS-056PROTACsBcr-Ablresistance-conferring mutationsK56232D-BCR-ABL cellsleukemiaInhibitorinhibitorinhibit

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