SDUY104
SDUY104 is an orally active amide-based allosteric inhibitor of SHP2 with an IC50 of 140 nM. SDUY104 impairs KRAS-driven pancreatic cancer cell proliferation via cell-cycle arrest and apoptosis. SDUY104 suppresses MAPK signaling and triggers compensatory PI3K-AKT activation. SDUY104 can be used for KRAS-mutant pancreatic cancer research.
For research use only. We do not sell to patients.
- Formula: C24H24ClN3O2S
- Molecular Weight:453.98
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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
Biological Activity
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SHP2 140 nM (IC50) |
p38 MAPK |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| BXPC-3 | IC50 |
61 μM
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Inhibits the growth of BXPC-3 cells for 48 hours.
Inhibits the growth of BXPC-3 cells for 48 hours.
|
42261691 |
| Panc203 | IC50 |
85 μM
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Inhibits Panc203 cells growth for 48 hours.
Inhibits Panc203 cells growth for 48 hours.
|
42261691 |
| SW1990 | IC50 |
73 μM
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Inhibits the growth of SW1990 cells for 48 hours.
Inhibits the growth of SW1990 cells for 48 hours.
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42261691 |
| Panc02 | IC50 |
63 μM
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Inhibits the growth of Panc02 cells for 48 hours.
Inhibits the growth of Panc02 cells for 48 hours.
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42261691 |
| CAPAN-1 | IC50 |
64 μM
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Inhibits the growth of CAPAN-1 cells for 48 hours.
Inhibits the growth of CAPAN-1 cells for 48 hours.
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42261691 |
| MIA PaCa-2 | IC50 |
55 μM
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Inhibits MIA PaCa-2 cells growth for 48 hours.
Inhibits MIA PaCa-2 cells growth for 48 hours.
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42261691 |
| PANC-1 | IC50 |
38 μM
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Inhibits the growth of PANC-1 cells for 48 hours.
Inhibits the growth of PANC-1 cells for 48 hours.
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42261691 |
| Hs 766 | IC50 |
43 μM
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Inhibits Hs 766 cell growth for 48 hours.
Inhibits Hs 766 cell growth for 48 hours.
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42261691 |
SDUY104 binds to and competitively occupies the SHP2 tunnel allosteric pocket with an IC50 of 1.5 μM[1].
SDUY104 (10 μM; 30 min) markedly inhibits SHP2 enzymatic activity with an IC50 of 140 nM[1].
SDUY104 (10 μM; 30 min) exhibits negligible inhibitory activity against other phosphatases (PTP1B, SHP1, TCPTP, LMWPTP) except SHP2[1].
SDUY104 (30 μM; 24 h) directly binds intracellular SHP2 and markedly stabilizes SHP2 against thermal denaturation in PDAC cells[1].
SDUY104 (48 h) elicits dose-dependent antiproliferative activity across KRAS mutant and wild-type PDAC cells with IC50s of 38-85 μM[1].
SDUY104 (30 μM; 24 h) induces G0/G1 arrest in BxPC-3 and PANC-1 cells[1].
SDUY104 (10-30 μM; 48 h) substantially induces late apoptosis in BxPC-3 cells while exhibiting minimal efficacy in PANC-1 cells at the same concentration[1].
SDUY104 (1-10 μM; 24-48 h) suppresses MAPK signaling but induces compensatory PI3K-AKT reactivation in BxPC-3 and PANC-1 cells[1].
SDUY104 (5 μM; 48 h) suppresses MAP signaling while paradoxically reactivates the PI3K-AKT pathway in PDAC cells via SHP2 inhibition[1].
SDUY104 (5-40 μM; 3 days) and Ulixertinib (HY-15816) act in combination to achieve synergistic suppression of PDAC cell proliferation[1].
SDUY104 (2-5 μM; 24 h) and Ulixertinib synergistically inhibit MAPK signaling in BxPC-3 and PANC-1 cells[1].
SDUY104 (30 μM; 72 h) exerts potentiated antiproliferative effects in BxPC-3 and PANC-1 cells in the presence of BKM-120 (HY-70063)[1].
SDUY104 (10 μM; 24 h) induces elevated AKT phosphorylation, and this effect is markedly counteracted by BKM-120 in both KRAS-mutant and wild-type cell lines[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:BxPC-3 cells, PANC-1 cells
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Concentration:10 μM, 30 μM
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Incubation Time:48 h
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Result:Robustly induced late-stage apoptosis in BxPC-3 cells while exhibiting weak effects in PANC-1 cells at the same concentration.
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Cell Line:BxPC-3 cells, PANC-1 cells
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Concentration:30 μM
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Incubation Time:24 h
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Result:Induced G0/G1 cell cycle arrest, with stronger activity in BxPC-3 than PANC-1 cells.
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Cell Line:BxPC-3 cells, PANC-1 cells
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Concentration:1 μM, 3 μM, 10 μM
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Incubation Time:24 h, 48 h
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Result:Dose-dependently inhibited ERK phosphorylation in BxPC-3 cells.
Dose-dependently inhibited ERK phosphorylation in KRAS mutant PANC-1 cells.
Significantly upregulated AKT phosphorylation in a dose-dependent manner in BxPC-3 and PANC-1 cells.
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Cell Line:PDAC cells
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Concentration:5 μM, 10 μM, 20 μM, 30 μM, 40 μM
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Incubation Time:3 days
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Result:Acted synergistically with Ulixertinib to inhibit PDAC cells proliferation.
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Cell Line:BxPC-3 cells, PANC-1 cells
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Concentration:2 μM, 5 μM
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Incubation Time:24 h
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Result:Acted synergistically with Ulixertinib to decrease phosphorylated RSK levels in BxPC-3 and PANC-1 cells.
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Cell Line:BxPC-3 cells, PANC-1 cells
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Concentration:30 μM
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Incubation Time:72 h
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Result:Induced 14% growth inhibition in BxPC-3 cells when used alone.
Reached a growth inhibition rate of 61% in BxPC-3 cells when co-administered with 100 nM BKM-120.
Yielded comparable synergistic antiproliferative effects in PANC-1 cells when combined with BKM-120.
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Cell Line:BxPC-3 cells, PANC-1 cells
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Concentration:10 μM
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Incubation Time:24 h
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Result:Raised AKT phosphorylation to approximately 141.8% of control levels in BxPC-3 cells.
Triggered AKT phosphorylation was markedly lowered to 35.9% after co-treatment with 1 μM BKM-120 in BxPC-3 cells.
Elevated AKT phosphorylation to 155.2% relative to controls in PANC-1 cells.
Elevated AKT phosphorylation in PANC-1 cells, and 1 μM BKM-120 lowered this phosphorylated level to 21.7%.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:5-week female BALB/c nude mice were acclimated for 1 week, inoculated with PANC-1 cells suspension (1×107 cells), and dosed at 9 weeks old (3 weeks post-inoculation) [1]
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Dosage:50 mg/kg (with 50 mg/kg Ulixertinib or 15 mg/kg BKM-120)
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Administration:p.o., once daily, for 3-4 weeks
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Result:Significantly suppressed tumor growth and reduced tumor volume, and its combination with Ulixertinib or BKM-120 yielded superior inhibitory effects.
Showed no significant body weight loss.
Significantly inhibited ERK phosphorylation by 68% but induced a 75% upregulation of AKT phosphorylation.
Further deepened MAPK pathway suppression when combined with Ulixertinib, while it effectively abolished AKT hyperphosphorylation upon coadministration with BKM-120.
Reduced cancer cell density and proliferation more potently when combined with Ulixertinib or BKM-120 than monotherapy, as verified by H&E, Ki67 and TUNEL staining.
Chemical Information
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Molecular Weight 453.98
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Formula C24H24ClN3O2S
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SMILES
NC1=CC=CC(SC2=CC=C(O2)C(N3CCC4(CC5=C([C@H]4N)C=CC=C5)CC3)=O)=C1Cl
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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)
SDUY104 Related Classifications
HY-184412 Related Classifications
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- SDUY104
- SDUY 104
- SDUY-104
- SHP2
- Apoptosis
- p38 MAPK
- SHP2 inhibitor
- MAPK
- PI3K-AKT
- antitumor activity
- cell cycle arrest
- apoptosis
- KRAS-mutant pancreatic cancer
- Ulixertinib
- BKM-120
- furanamide derivatives
- KRAS mutant PDAC cells
- phosphatases
- BKM-120 cells
- BxPC-3 cells
- AKT phosphorylation
- ERK phosphorylation
- tumor
- Inhibitor
- inhibitor
- inhibit