Réactifs et instruments pour l'immunologie, la biologie cellulaire et la biologie moléculaire.

SHP099 [1801747-42-1]

Imprimer

Référence HY-100388-1mL

Conditionnement : 10mM/1mL

Marque : MedChemExpress

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Description

SHP099 is an allosteric SHP2 inhibitor, with IC₅₀s of 0.690, 1.241, 0.416, 1.968, 2.896 μM for SHP2, SHP2^D61Y, SHP2E69K, SHP2^A72V, SHP2^E76K. SHP099 inhibits cancer cell growth, such as MV4-11 and TF-1 cell (IC₅₀: 0.32 and 1.73 μM). SHP099 inhibits RAS-ERK signaling and inhibits tumor growth^[1]^[2].

IC₅₀ & Target

IC50: 70 nM (SHP2)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
4T1	IC₅₀	119.3 μM Compound: SHP099	Antiproliferative activity against mouse 4T1 cells assessed as cell viability incubated for 72 hrs by CCK-8 assay Antiproliferative activity against mouse 4T1 cells assessed as cell viability incubated for 72 hrs by CCK-8 assay	[PMID: 36097406]
4T1	IC₅₀	32.4 μM Compound: SHP099	Antiproliferative activity against mouse 4T1 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay Antiproliferative activity against mouse 4T1 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay	[PMID: 39066713]
5637	IC₅₀	159.1 μM Compound: SHP099	Antiproliferative activity against human 5637 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay Antiproliferative activity against human 5637 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay	[PMID: 39066713]
A549	IC₅₀	> 50 μM Compound: SHP099	Antiproliferative activity against human A549 cells assessed as inhibition of cell growth measured after 72 hrs by CCK8 method Antiproliferative activity against human A549 cells assessed as inhibition of cell growth measured after 72 hrs by CCK8 method	[PMID: 37390510]
ASPC1	IC₅₀	64.04 μM Compound: SHP099	Antiproliferative activity against human ASPC1 cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay Antiproliferative activity against human ASPC1 cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay	[PMID: 36097406]
BXPC-3	IC₅₀	72.86 μM Compound: SHP099	Antiproliferative activity against human BXPC-3 cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay Antiproliferative activity against human BXPC-3 cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay	[PMID: 36097406]
BaF3	IC₅₀	19.86 μM Compound: SHP-099	Cytotoxicity against mouse BaF3 cells assessed as inhibition of cell proliferation incubated for 48 hrs by MTT assay Cytotoxicity against mouse BaF3 cells assessed as inhibition of cell proliferation incubated for 48 hrs by MTT assay	[PMID: 33582386]
Capan-2	IC₅₀	15.67 μM Compound: SHP-099	Cytotoxicity against human Capan-2 cells harbouring K-ras mutant assessed as reduction in cell viability incubated for 144 hrs Cytotoxicity against human Capan-2 cells harbouring K-ras mutant assessed as reduction in cell viability incubated for 144 hrs	[PMID: 33582386]
Detroit 562	IC₅₀	6.47 μM Compound: 2; SHP099	Antiproliferative activity against human Detroit 562 cells after 24 hrs by Celltiter-Glo assay Antiproliferative activity against human Detroit 562 cells after 24 hrs by Celltiter-Glo assay	[PMID: 30688459]
HCT-116	IC₅₀	76.9 μM Compound: SHP099	Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay	[PMID: 39066713]
HepG2	IC₅₀	36.4 μM Compound: SHP099	Antiproliferative activity against human HepG2 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay Antiproliferative activity against human HepG2 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay	[PMID: 39066713]
MDA-MB-468	IC₅₀	110.7 μM Compound: SHP099	Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay	[PMID: 39066713]
MDA-MB-468	IC₅₀	29.9 μM Compound: SHP099	Antiproliferative activity against human MDA-MB-468 cells assessed as reduction in cell viability after 2 to 4 days by CCK-8 assay Antiproliferative activity against human MDA-MB-468 cells assessed as reduction in cell viability after 2 to 4 days by CCK-8 assay	[PMID: 31784318]
MDA-MB-468	IC₅₀	31.76 μM Compound: SHP099	Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell growth measured after 72 hrs by CCK8 method Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell growth measured after 72 hrs by CCK8 method	[PMID: 37390510]
MDA-MB-468	IC₅₀	49.6 μM Compound: SHP099	Antiproliferative activity against human MDA-MB-468 3D spheroids assessed as reduction in cell viability after 2 to 4 days by CCK-8 assay Antiproliferative activity against human MDA-MB-468 3D spheroids assessed as reduction in cell viability after 2 to 4 days by CCK-8 assay	[PMID: 31784318]
MIA PaCa-2	IC₅₀	41.9 μM Compound: SHP099	Antiproliferative activity against human MIA PaCa-2 cells harboring KRASG12C mutant assessed as inhibition of cell growth incubated for 72 hrs by CellTiter-LumiII Luminescent assay Antiproliferative activity against human MIA PaCa-2 cells harboring KRASG12C mutant assessed as inhibition of cell growth incubated for 72 hrs by CellTiter-LumiII Luminescent assay	[PMID: 37754066]
MOLM-14	IC₅₀	0.9 μM Compound: SHP099	Antiproliferative activity against human MOLM14 cells after 3 days by CellTiter-Glo luminescence assay Antiproliferative activity against human MOLM14 cells after 3 days by CellTiter-Glo luminescence assay	[PMID: 29089257]
MV4-11	IC₅₀	0.24 μM Compound: SHP099	Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability incubated for 72 hrs in presence of SAHA by CCK-8 assay Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability incubated for 72 hrs in presence of SAHA by CCK-8 assay	[PMID: 36097406]
MV4-11	IC₅₀	0.475 nM Compound: 1; SHP099	Antiproliferative activity against human MV4-11 cells assessed as inhibition of cell proliferation measured after 72 hrs by MTS assay Antiproliferative activity against human MV4-11 cells assessed as inhibition of cell proliferation measured after 72 hrs by MTS assay	[PMID: 33780898]
MV4-11	IC₅₀	0.572 μM Compound: 1; SHP099	Cytotoxicity against human MV4-11 cells assessed as cell viability measured after 72 hrs by MTS assay Cytotoxicity against human MV4-11 cells assessed as cell viability measured after 72 hrs by MTS assay	[PMID: 33780898]
MV4-11	IC₅₀	0.803 μM Compound: 1; SHP099	Cytotoxicity against CRBN knock out human MV4-11 cells assessed as cell viability measured after 72 hrs by MTS assay Cytotoxicity against CRBN knock out human MV4-11 cells assessed as cell viability measured after 72 hrs by MTS assay	[PMID: 33780898]
MV4-11	IC₅₀	1 μM Compound: 1; SHP099	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]
MV4-11	IC₅₀	1.75 μM Compound: SHP099	Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay	[PMID: 36097406]
MV4-11	IC₅₀	2.78 μM Compound: SHP099	Antiproliferative activity against human MV4-11 cells assessed as inhibition of cell growth measured after 72 hrs by CCK8 method Antiproliferative activity against human MV4-11 cells assessed as inhibition of cell growth measured after 72 hrs by CCK8 method	[PMID: 37390510]
NCI-H358	IC₅₀	> 50 μM Compound: SHP099	Antiproliferative activity against human NCI-H358 cells assessed as inhibition of cell growth measured after 72 hrs by CCK8 method Antiproliferative activity against human NCI-H358 cells assessed as inhibition of cell growth measured after 72 hrs by CCK8 method	[PMID: 37390510]
RT-4	IC₅₀	43.9 μM Compound: SHP099	Antiproliferative activity against human RT-4 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay Antiproliferative activity against human RT-4 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay	[PMID: 39066713]
SW1990	IC₅₀	103.5 μM Compound: SHP099	Antiproliferative activity against human SW1990 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay Antiproliferative activity against human SW1990 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay	[PMID: 39066713]
SW1990	IC₅₀	104.8 μM Compound: SHP099	Antiproliferative activity against human SW1990 cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay Antiproliferative activity against human SW1990 cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay	[PMID: 36097406]
SW480	IC₅₀	104.6 μM Compound: SHP099	Antiproliferative activity against human SW480 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay Antiproliferative activity against human SW480 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay	[PMID: 39066713]
T-24	IC₅₀	225.2 μM Compound: SHP099	Antiproliferative activity against human T24 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay Antiproliferative activity against human T24 cells assessed as inhibition of cell growth measured after 48 hrs by CCK-8 assay	[PMID: 39066713]

In Vitro

The X-ray co-crystal for SHP099 with SHP2 reveals a new interaction with the basic amine and the Phe113 backbone carbonyl. SHP099 shows inhibition of cell proliferation (KYSE-520 model) with an IC₅₀ of 1.4 μM. SHP099 shows high solubility and high permeability with no apparent efflux in Caco-2 cells^[1]. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells^[2].

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

Solvant et solubilité

In Vitro:

DMSO : 12 mg/mL (34.07 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : < 0.1 mg/mL (insoluble)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.8388 mL	14.1941 mL	28.3881 mL
5 mM	0.5678 mL	2.8388 mL	5.6776 mL
10 mM	0.2839 mL	1.4194 mL	2.8388 mL

View the Complete Stock Solution Preparation Table

* 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.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 1.2 mg/mL (3.41 mM); Clear solution

This protocol yields a clear solution of ≥ 1.2 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 1.2 mg/mL (3.41 mM); Clear solution

This protocol yields a clear solution of ≥ 1.2 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 1.2 mg/mL (3.41 mM); Clear solution

This protocol yields a clear solution of ≥ 1.2 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 4

Add each solvent one by one: 5% DMSO 40% PEG300 5% Tween-80 50% Saline
Solubility: ≥ 0.67 mg/mL (1.90 mM); Clear solution
Protocol 5

Add each solvent one by one: 5% DMSO 95% (20% SBE-β-CD in Saline)
Solubility: ≥ 0.67 mg/mL (1.90 mM); Clear solution
Protocol 6

Add each solvent one by one: 1% DMSO 99% Saline
Solubility: ≥ 0.13 mg/mL (0.37 mM); Clear solution

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 0.5% CMC-Na/saline water
Solubility: 10 mg/mL (28.39 mM); Suspended solution; Need ultrasonic

Pureté et documentation

Purity: 99.81%

Fiche technique (279 KB) SDS (393 KB)

COA (249 KB) LCMS (95 KB)

Instruction de manipulation (2659 KB)

Références

[1]. Chen YN, et al. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature. 2016 Jul 7;535(7610):148-52. [Content Brief]

[2]. Sun X, et al. Selective inhibition of leukemia-associated SHP2E69K mutant by the allosteric SHP2 inhibitor SHP099. Leukemia. 2018 May;32(5):1246-1249. [Content Brief]

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Référence HY-100388-1mL

Marque : MedChemExpress

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