LWY713
LWY713 is a FLT3 PROTAC degrader with a DC50 of 0.64 nM. LWY713 selectively induces FLT3 degradation in a cereblon- and proteasome-dependent manner. LWY713 induces G0/G1 cell cycle arrest and triggers apoptosis. LWY713 upregulates PARP and cleaved caspase 3, and inhibits the phosphorylation of FLT3, STAT5, AKT and Erk. LWY713 exhibits antitumor activity in xenograft mouse models. LWY713 can be used for the research of acute myeloid leukemia.
(Pink: FLT3 ligand (HY-12432); Blue: Cereblon ligand (HY-W039233); Black: linker (HY-W015967)).
연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.
- 화학식: C43H54N10O8
- 분자량:838.95
-
보관:
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]
-
Biological Activity
-
Chemical Information
- 순도&문서
- References
-
Help & FAQs
Biological Activity
|
Cereblon |
Caspase 3 |
STAT5 |
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| MV4-11 | IC50 |
1.5 nM
Compound: 13ba; LWY713
|
Antiproliferative activity against human MV4-11 cells assessed as inhibition of cell proliferation incubated for 72 hrs by CCK8 assay
Antiproliferative activity against human MV4-11 cells assessed as inhibition of cell proliferation incubated for 72 hrs by CCK8 assay
|
[PMID: 38007910] |
LWY713 (0.04-50 nM; 24 h) potently degrades FLT3 in AML MV4-11 cells with a DC50 of 0.64 nM and a Dmax of 94.8%[1].
LWY713 (1-10 nM; 2-20 h for MDA-MB-231 cells; 0-24 h for Raji cells) selectively degrades FLT3 but does not degrade AXL, ALK, or LTK in AXL-overexpressing MDA-MB-231 cells and ALK/LTK-overexpressing Raji cells[1].
LWY713 (72 h) potently inhibits the proliferation of AML MV4-11 cells with an IC50 of 1.50 nM[1].
LWY713 (0.08-50 nM; 24 h) potently inhibits FLT3 downstream signaling in AML MV4-11 cells by degrading FLT3 and reducing phosphorylation of FLT3, STAT5, AKT, and Erk[1].
LWY713 (0.08-10 nM; 48 h) dose-dependently induces apoptosis in AML MV4-11 cells, with increased levels of activated apoptotic proteins at 2 nM and 10 nM[1].
LWY713 (0.08-2 nM; 24 h) dose-dependently induces G0/G1-phase cell cycle arrest in AML MV4-11 cells, with 82.1% of cells in G0/G1 phase at 2 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:AML MV4-11 cells (FLT3-ITD mutation)
-
Concentration:0.04, 0.08, 0.15, 0.31, 0.62, 1.25, 2.5, 5, 10, 25, 50 nM
-
Incubation Time:24 h
-
Result:Induced dose-dependent degradation of FLT3 protein, with a half-maximal degradation concentration (DC50) of 0.64 nM and a maximum degradation efficiency (Dₘₐₓ) of 94.8%.
-
Cell Line:AML MV4-11 cells (FLT3-ITD mutation)
-
Concentration:1, 10 nM
-
Incubation Time:0. 2, 4, 8, 12, 16, 20 h
-
Result:Induced rapid FLT3 degradation within 2 h at concentrations as low as 1 nM, with maximum degradation efficiency observed at 20 h.
-
Cell Line:AXL-overexpressing MDA-MB-231 cells, ALK/LTK-overexpressing Raji lymphoma cells
-
Concentration:1, 10 nM
-
Incubation Time:0. 2, 4, 8, 12, 16, 20 h (MDA-MB-231 cells); 0, 2, 4, 8, 12, 24 h (Raji cells)
-
Result:Did not degrade AXL in MDA-MB-231 cells, nor did it degrade ALK or LTK in Raji cells at the tested concentrations and timepoints.
-
Cell Line:AML MV4-11 cells (FLT3-ITD mutation)
-
Concentration:0, 0.08, 0.4, 2, 10 nM
-
Incubation Time:48 h
-
Result:Induced MV4-11 cell apoptosis in a dose-dependent manner, with 24.8% and 33.1% apoptosis observed at 2 nM and 10 nM, respectively.
Upregulated cleaved PARP and cleaved caspase 3 significantly at 2 nM and 10 nM.
-
Cell Line:AML MV4-11 cells (FLT3-ITD mutation)
-
Concentration:0, 0.08, 0.4, 2 nM
-
Incubation Time:24 h
-
Result:Induced G0/G1-phase arrest in MV4-11 cells in a dose-dependent manner, with 79.8% and 82.1% of cells in G0/G1 phase at 0.4 nM and 2 nM, respectively.
-
Cell Line:AML MV4-11 cells (FLT3-ITD mutation)
-
Concentration:0, 0.08, 0.4, 2, 10, 50 nM
-
Incubation Time:24 h
-
Result:Induced dose-dependent FLT3 degradation and suppressed phosphorylation of FLT3, STAT5, AKT, and Erk, with no upregulation of FLT3 or phosphorylated AKT observed.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:NOD/SCID (female, immunodeficient, inoculated subcutaneously with 5 × 106 MV4-11 cells, tumors grown to 200 mm3 prior to treatment)[1]
-
Dosage:6 mg/kg
-
Administration:i.p.; daily; 21 days
-
Result:Significantly reduced tumor volume compared to the vehicle group.
Showed no obvious weight loss during the 21-day study period.
Chemical Information
-
분자량 838.95
-
화학식 C43H54N10O8
-
SMILES
O=C1C2=CC=CC(OCC(N3CCN(C4CCN(C5=CC=C(C=C5OC)NC6=C(C(N)=O)N=C(CC)C(NC7CCOCC7)=N6)CC4)CC3)=O)=C2CN1C8C(NC(CC8)=O)=O
-
선적
Room temperature in continental US; may vary elsewhere.
-
보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
LWY713 Related Classifications
HY-157213 Related Classifications
Powered by Bioz