Name: SHP099 Hydrochloride
Brand: Selleck Chemicals
SKU: S8278
Availability: InStock
Rating: 5 (50 reviews)

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Quality Control

Batch: Purity: 99.95%

99.95

Products Often Used Together with SHP099 Hydrochloride

Omipalisib (GSK2126458)

It and Omipalisib reduce tumor growth in vivo.

SX-682

It and SX-682 block granulocytic myeloid-derived suppressor cells (gMDSC) immigration.

Related Targets	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism Drug Metabolite
Other phosphatase Products	Osunprotafib (ABBV-CLS-484) RMC-4550 SHP099 GSK2830371 β-Glycerophosphate sodium salt hydrate NSC87877 Batoprotafib (TNO155) TPI-1 Sanguinarine chloride Raphin1

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
MGH049-1A	Function assay	5 μM	14 days	As a single agent, SHP099 had minimal effect on cell proliferation	29505033
MGH073-2B	Function assay	5 μM	14 days	As a single agent, SHP099 had minimal effect on cell proliferation	29505033
MGH065-1B	Function assay	5 μM	14 days	As a single agent, SHP099 had minimal effect on cell proliferation	29505033
MGH045-2A	Function assay	5 μM	14 days	As a single agent, SHP099 had minimal effect on cell proliferation	29505033
U2OS cells	Function assay	0, 1, 3, 6, 12, 25, 50 μM		SHP099 reduces pErk levels in wild-type U2OS cells.	30375388
KYSE-520	Proliferation assay		5 days	inhibition of cell proliferation with an IC50 of 1.4 μM	27347692
MOLM14	Antiproliferative assay		3 days	Antiproliferative activity against human MOLM14 cells after 3 days by CellTiter-Glo luminescence assay, IC50 = 0.9 μM.	29089257
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 78 mg/mL (200.65 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : 6 mg/mL

Ethanol : Insoluble

DMSO : 10 mg/mL (25.72 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : 10 mg/mL (Ultrasonic and heating for 10 minutes, at 60℃.)

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	2.000mg/ml (5.15mM)	Taking the 1 mL working solution as an example, add 50 μL of 40 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

+

%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	388.72	Formula	C₁₆H₂₀Cl₃N₅	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	2200214-93-1	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	Cl.CC1(N)CCN(CC1)C2=CN=C(C(=N2)N)C3=CC=CC(=C3Cl)Cl

Mechanism of Action

Targets/IC₅₀/Ki	SHP-2 (Cell-free assay) 0.07 μM
In vitro	SHP099 shows inhibition of cell proliferation (KYSE-520 model) with an IC50 of 1.4 μM. In both phosphatase and kinase panels, no biochemical inhibitory activity is evident, suggesting that the aminopyrazine series(SHP099) is quite selective for SHP2. Moreover, SHP099 shows high solubility (>0.5 mM in pH 6.8 buffer) and high permeability with no apparent efflux in Caco-2 cells. SHP099 stabilizes SHP2 in an auto-inhibited conformation. SHP099 suppresses RAS-ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro. SHP099 only has modest activity against 5HT3 when profiled against a preclinical safety pharmacology panel representing 49 common adverse drug reaction targets. SHP099 shows no activity against SHP1, the closest homologue of SHP2 sharing 61% amino acid sequence identity, supporting its high degree of target selectivity. It inhibits p-ERK with an IC50 of ~0.25 μM in SHP2-dependent MDA-MB-468 and KYSE520 cells, but not in A2058 cells. No effect is observed on p-AKT levels across the same cells. SHP099 inhibits MAPK signalling and proliferation in RTK-dependent cells through direct on-target inhibition of SHP2.
In vivo	SHP099 shows acceptable oral exposure (5 mg/kg PO, 565 μM/h) and bioavailability (46% F). SHP099 is a potent, selective, highly soluble, orally bioavailable, and efficacious SHP2 inhibitor exhibiting dose-dependent pathway inhibition and antitumor activity in xenograft models. Orally administered SHP099 shows dose-dependent anti-tumour activity in the KYSE520 xenograft model and is well tolerated.
References	[1] https://pubmed.ncbi.nlm.nih.gov/27347692/ [2] https://pubmed.ncbi.nlm.nih.gov/27362227/

Applications

Methods	Biomarkers	PMID
Western blot	EGFR / pEGFR / GAB1 / pSHP2 / GRB2 / SOS1 pMEK / MEK / pERK / Erk pERK / Bcl-xL / p85 PARP	30605687
Growth inhibition assay	Cell viability	29568093
Immunofluorescence	insulin receptor	30931927