Art. -Nr.: HY-145162

SHP2-D26

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SHP2-D26 is a SHP2 PROTAC degrader with DC₅₀ values of 6.0 nM (KYSE520 cells) and 2.6 nM (MV4;11 cells), respectively. SHP2-D26 inhibits ERK phosphorylation, upregulates Bim levels, downregulates Mcl-1 levels, and induces cell cycle arrest and apoptosis. SHP2-D26 can be used in studies related to esophageal cancer, acute myeloid leukemia and non-small cell lung cancer.
(Pink: SHP2 ligand (HY-176797); Blue: VHL ligand (HY-150803); Black: linker).

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Reinheit: 95.83%
CAS. Nr.: 2458219-65-1
Formel: C₅₆H₇₉ClN₁₂O₆S₂
Molecular Weight:1115.89

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

SHP2-D26 Chemical Structure

CAS. Nr.: 2458219-65-1

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Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (1)
Lösungsmittel & Löslichkeit
- In Vitro
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

SHP2-D26 is a SHP2 PROTAC degrader with DC₅₀ values of 6.0 nM (KYSE520 cells) and 2.6 nM (MV4;11 cells), respectively. SHP2-D26 inhibits ERK phosphorylation, upregulates Bim levels, downregulates Mcl-1 levels, and induces cell cycle arrest and apoptosis. SHP2-D26 can be used in studies related to esophageal cancer, acute myeloid leukemia and non-small cell lung cancer^[1]^[2]. (Pink: SHP2 ligand (HY-176797); Blue: VHL ligand (HY-150803); Black: linker).

IC₅₀ & Target^[1]^[2]

VHL

Mcl-1

Bim

Alle PROTACs Isoform-spezifische Produkte anzeigen :

Alle ERK Isoform-spezifische Produkte anzeigen :

Alle Bcl-2 Family Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
KYSE-520 cell line	IC₅₀	0.66 μM Compound: 26; SHP2-D26	Growth inhibition of human KYSE520 cells measured after 4 days by WST8 assay Growth inhibition of human KYSE520 cells measured after 4 days by WST8 assay	[PMID: 32437146]
MV4-11	DC₅₀	2.6 nM Compound: 26; SHP2-D26	Protac activity at VHL1/SHP2 in human MV4-11 cells assessed as induction of SHP2 degradation measured after 12 hrs by Western blot analysis Protac activity at VHL1/SHP2 in human MV4-11 cells assessed as induction of SHP2 degradation measured after 12 hrs by Western blot analysis	[PMID: 32437146]
MV4-11	IC₅₀	9.9 nM Compound: 26; SHP2-D26	Growth inhibition of human MV4-11 cells measured after 4 days by WST8 assay Growth inhibition of human MV4-11 cells measured after 4 days by WST8 assay	[PMID: 32437146]

In Vitro

SHP2-D26 (100 nM; 2-24 h) induces rapid degradation of SHP2 protein in KYSE520 esophageal cancer cells and MV4;11 acute myeloid leukemia cells, with nearly complete depletion of the protein observed at 8 h of treatment^[1].
SHP2-D26 (3 nM-1000 nM; 48 h) effectively reduces p-ERK levels in KYSE520 esophageal cancer cells and MV4;11 acute myeloid leukemia cells^[1].
SHP2-D26 (0.001 μM-100 μM; 4 days) inhibits the proliferation of KYSE520 esophageal cancer cells and MV4;11 acute myeloid leukemia cells, with IC₅₀ values of 0.66 μM and 9.9 nM^[1].
SHP2-D26 (72 h) potently inhibits the growth of all tested human non-small cell lung cancer (NSCLC) cell lines, with IC₅₀ values all < 8 μM; it exhibits stronger activity against PC-9, H1648, H1792 and HCC827 cell lines, with IC₅₀ values ≤ 4 μM^[2].
SHP2-D26 (0.1-4 μM; 2 h-24 h) sustainably inhibits the p70S6K/S6 signaling pathway in sensitive human non-small cell lung cancer cell lines (PC-9, H1792, HCC827), whereas exerts cell line-dependent effects on the ERK1/2 and Akt signaling pathways^[2].
SHP2-D26 (1 μM; 6 h) increases the stability of Bim protein and decreases the stability of Mcl-1 protein in human non-small cell lung cancer cell lines HCC827 and PC-9^[2].
SHP2-D26 (1-7.5 μM; 4-48 h) induces apoptosis in human non-small cell lung cancer cell lines (PC-9, H1792, HCC827) by upregulating Bim levels and downregulating Mcl-1 levels, and both the upregulation of Bim and downregulation of Mcl-1 are essential for its pro-apoptotic activity^[2].
SHP2-D26 (0.075 μM-6 μM; 16 h-12 days) acts synergistically with Osimertinib (HY-15772) to reduce cell viability, inhibit colony formation and enhance apoptosis in osimertinib-resistant human non-small cell lung cancer cell lines PC-9/AR, PC-9/GR/AR, PC-9/3 M and HCC827/AR^[2].

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

Western Blot Analysis^[1]

Cell Line:

KYSE520 esophageal cancer cells and MV4;11 acute myeloid leukemia cells
Concentration:

100 nM
Incubation Time:

2 h, 4 h, 8 h, 12 h, 24 h
Result:

Reduced SHP2 protein levels within 4 h, and achieved essentially complete SHP2 depletion after 8 h of treatment.
Reduced SHP2 protein levels within 4 h, and achieved essentially complete SHP2 depletion after 8 h of treatment, similar to kinetics observed in KYSE520 cells.

Western Blot Analysis^[1]

Cell Line:

KYSE520 esophageal cancer cells
Concentration:

10 nM, 30 nM, 100 nM, 300 nM, 1000 nM
Incubation Time:

48 h
Result:

Dose-dependently inhibited ERK phosphorylation, with 100 nM SHP2-D26 effectively reducing p-ERK levels; this potency was > 30-times higher than the SHP2 inhibitor SHP099 (HY-100388).

Western Blot Analysis^[1]

Cell Line:

MV4;11 acute myeloid leukemia cells
Concentration:

3 nM, 10 nM, 30 nM, 100 nM, 300 nM
Incubation Time:

48 h
Result:

Dose-dependently inhibited ERK phosphorylation, with 100 nM SHP2-D26 completely blocking p-ERK levels; this potency was > 30-times higher than the SHP2 inhibitor SHP099.

Western Blot Analysis^[2]

Cell Line:

human NSCLC cell lines (PC-9, H1792, HCC827, H157, H1944, H1651, H1975)
Concentration:

0.1, 0.5, 1, 2 and 4 μM
Incubation Time:

2, 4, 8, 16 and 24 h
Result:

Consistently decreased phosphorylated S6 (p-S6) levels in all sensitive NSCLC cell lines (PC-9, H1792, HCC827), and weakly in H1975, but not in other less sensitive lines.
Decreased phosphorylated p70S6K (p-p70S6K) in sensitive lines, with weak suppression of phosphorylated mTOR (p-mTOR) only in HCC827.
Reduced p-ERK1/2 in H1792 but only weakly in PC-9 and HCC827; minimally decreased p-Akt in PC-9 but increased p-Akt in H1792.
Decreased total ERK1/2 levels in PC-9 and H1792.

Apoptosis Analysis^[2]

Cell Line:

human NSCLC cell lines (PC-9, H1792, HCC827, Bim-knockout PC-9, Mcl-1-overexpressing PC-9)
Concentration:

1, 2.5, 5, 7.5 μM
Incubation Time:

4, 8, 12, 16 and 48 h
Result:

Induced apoptosis in sensitive NSCLC cell lines in a concentration-dependent manner: increased Annexin V-positive cells and cleaved PARP/caspase-3 in PC-9 at 5 μM and 7.5 μM; induced similar effects in H1792 and HCC827 at 5 μM.
Increased Bim levels and decreased Mcl-1 levels in sensitive lines, with Bim elevation detected at concentrations as low as 1 μM and Mcl-1 reduction detected at 5 μM or higher in PC-9.
Reduced sensitivity to apoptosis and cell number reduction in Bim-knockout PC-9 cells; attenuated apoptosis and reduced sensitivity to cell survival inhibition in Mcl-1-overexpressing PC-9 cells.

In Vivo

SHP2-D26 (20-40 mg/kg; intraperitoneally injected once daily for the first 10 days, then switched to intravenous injection twice weekly, for a total of 28-35 days) moderately but significantly inhibits the growth of PC-9 non-small cell lung cancer xenografts in nude mice^[2].
SHP2-D26 (30 mg/kg; i.p.; once daily; for 24 consecutive days) exhibits only very low monotherapy activity against Osimertinib-resistant PC-9/AR non-small cell lung cancer xenografts in nude mice, but when combined with Osimertinib, it significantly inhibits tumor growth by enhancing SHP2 degradation, upregulating Bim, downregulating Mcl-1 and inducing apoptosis^[2].

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

Animal Model:

Nude mice^[2]
Dosage:

20 mg/kg; 40 mg/kg
Administration:

i.p.; once daily for first 10 days, then i.v.; twice weekly until study end (20 mg/kg); i.p.; once daily throughout study (40 mg/kg)
Result:

Significantly reduced PC-9 tumor volume to a mean end-of-study volume of ~520 mm³ compared to ~850 mm³ for vehicle.
Significantly reduced PC-9 tumor weight to a mean weight of ~0.27 g compared to ~0.55 g for vehicle.
Significantly reduced PC-9 tumor volume to a mean end-of-study volume of ~650 mm³ compared to ~850 mm³ for vehicle.
Significantly reduced PC-9 tumor weight to a mean weight of ~0.35 g compared to ~0.55 g for vehicle.
Induced SHP2 degradation in tumor tissue to a SHP2/GAPDH ratio of ~0.7 for 20 mg/kg and ~0.2 for 40 mg/kg compared to ~1.8 for vehicle.
Significantly increased Bim levels to a Bim/GAPDH ratio of ~0.6 compared to ~0.3 for vehicle.
Significantly reduced Mcl-1 levels to a Mcl-1/GAPDH ratio of ~0.2 compared to ~2.0 for vehicle.
Induced cleaved PARP.
Reduced p-S6 levels, with the 40 mg/kg dose causing a significant reduction to a p-S6/S6 ratio of ~0.2 compared to ~1.0 for vehicle.
Caused no apparent body weight loss in either treatment group.

Animal Model:

Nude mice^[2]
Dosage:

30 mg/kg
Administration:

i.p.; once daily; 24 consecutive days
Result:

Minimally reduced PC-9/AR tumor volume to a mean end-of-study volume of ~820 mm³ compared to ~950 mm³ for vehicle.
Minimally reduced PC-9/AR tumor weight to a mean weight of ~0.5 g compared to ~0.7 g for vehicle.
When combined with Osimertinib, significantly reduced PC-9/AR tumor volume to a mean end-of-study volume of ~320 mm³ compared to ~950 mm³ for vehicle.
When combined with osimertinib, significantly reduced PC-9/AR tumor weight to a mean weight of ~0.3 g compared to ~0.7 g for vehicle.
Induced SHP2 degradation in tumor tissue to a SHP2/Actin ratio of ~0.2 for single agent and ~0.2 for combination compared to ~1.0 for vehicle.
When combined with Osimertinib, significantly elevated Bim levels to a Bim/GAPDH ratio of ~1.2 compared to ~0.5 for vehicle.
When combined with Osimertinib, significantly reduced Mcl-1 levels to a Mcl-1/GAPDH ratio of ~0.2 compared to ~1.1 for vehicle.
Induced cleaved PARP when combined with Osimertinib.
When combined with Osimertinib, significantly reduced p-S6 levels to a p-S6/S6 ratio of ~0 compared to ~0.8 for vehicle.
Caused no apparent body weight loss in the SHP2-D26 treatment group or combination group.

Chemical Information

CAS. Nr. 2458219-65-1
Appearance Solid
Molecular Weight 1115.89
Formel C₅₆H₇₉ClN₁₂O₆S₂
Color Off-white to light yellow
SMILES

ClC(C(SC1=NC=C(N2CCC(N)(CC2)C)N=C1N)=CC=C3)=C3NC(CCC(N(CC4)CCN4CCCCCCCCC(N[C@@H](C(C)(C)C)C(N5[C@@H](C[C@H](C5)O)C(N[C@H](C6=CC=C(C7=C(C)N=CS7)C=C6)C)=O)=O)=O)=O)=O
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Publications (1)

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Journal Impact Factor

J Biol Chem

Bivalent target-binding bioPROTACs induce potent degradation of oncogenic SHP2. [Abstract]

2024 Jul 30:107616. PMID: 39089586

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 83.33 mg/mL (74.68 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

0.8961 mL

4.4807 mL

8.9615 mL

5 mM

0.1792 mL

0.8961 mL

1.7923 mL

10 mM

0.0896 mL

0.4481 mL

0.8961 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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)}

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (285 KB)
SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 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]. Wang M, et al. Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein. Journal of medicinal chemistry. 2020 Jul 23;63(14):7510-7528. [Content Brief]

[2]. Deng Y, et al. Therapeutic efficacy of the novel SHP2 degrader SHP2-D26, alone or in combination, against lung cancer is associated with modulation of p70S6K/S6, Bim and Mcl-1. Cancer gene therapy. 2022 Nov;29(11):1558-1569.

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.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	0.8961 mL	4.4807 mL	8.9615 mL	22.4036 mL
	5 mM	0.1792 mL	0.8961 mL	1.7923 mL	4.4807 mL
	10 mM	0.0896 mL	0.4481 mL	0.8961 mL	2.2404 mL
	15 mM	0.0597 mL	0.2987 mL	0.5974 mL	1.4936 mL
	20 mM	0.0448 mL	0.2240 mL	0.4481 mL	1.1202 mL
	25 mM	0.0358 mL	0.1792 mL	0.3585 mL	0.8961 mL
	30 mM	0.0299 mL	0.1494 mL	0.2987 mL	0.7468 mL
	40 mM	0.0224 mL	0.1120 mL	0.2240 mL	0.5601 mL
	50 mM	0.0179 mL	0.0896 mL	0.1792 mL	0.4481 mL
	60 mM	0.0149 mL	0.0747 mL	0.1494 mL	0.3734 mL

Keywords

SHP2-D26

1 Cited Publications

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SHP2-D26

PROTAC Library

Publications Citing Use of MedChemExpress (MCE) SHP2-D26

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle ERK Isoform-spezifische Produkte anzeigen

Alle Bcl-2 Family Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (1)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

SHP2-D26

PROTAC Library

Publications Citing Use of MedChemExpress (MCE) SHP2-D26

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle ERK Isoform-spezifische Produkte anzeigen

Alle Bcl-2 Family Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (1)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

SHP2-D26 Related Classifications

HY-145162 Related Classifications