Home Metabolism phosphatase inhibitor SHP099 HCl For research use only.

SHP099 HCl

SHP099 is a highly potent, selective and orally bioavailable small-molecule SHP2 inhibitor with an IC50 value of 0.071 μM and shows no activity against SHP1.

SHP099 HCl Chemical Structure

SHP099 HCl Chemical Structure

CAS No. 2200214-93-1

Purity & Quality Control

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SHP099 HCl and SX-682 block granulocytic myeloid-derived suppressor cells (gMDSC) immigration.

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SHP099 HCl Related Products

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation 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

Biological Activity

Description SHP099 is a highly potent, selective and orally bioavailable small-molecule SHP2 inhibitor with an IC50 value of 0.071 μM and shows no activity against SHP1.
Targets
SHP-2 [1]
(Cell-free assay)
0.07 μM
In vitro
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[1]. 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[2].
Cell Research Cell lines KYSE-520 cells
Concentrations 20, 6.6, 2.2, 0.74, 0.24, 0.08, and 0.027 μM
Incubation Time 2 h
Method

KYSE-520 cells (30,000 cells/well) are grown in 96-well plate culture overnight and treated with SHP2 inhibitors at concentrations of 20, 6.6, 2.2, 0.74, 0.24, 0.08, and 0.027 μM for 2 h at 37 °C. Incubations are terminated by addition of 30 μL of lysis buffer supplied with the SureFire p-ERK assay kit.
Experimental Result Images Methods Biomarkers Images PMID
Western blot pERK / Bcl-xL / p85 PARP pMEK / MEK / pERK / Erk EGFR / pEGFR / GAB1 / pSHP2 / GRB2 / SOS1 29568093
Growth inhibition assay Cell viability 29568093
Immunofluorescence insulin receptor 30931927
In Vivo
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[1]. Orally administered SHP099 shows dose-dependent anti-tumour activity in the KYSE520 xenograft model and is well tolerated[2].
Animal Research Animal Models Nude mice (Tumor Xenograft)
Dosages 10, 30, or 100 mg/kg qd
Administration by oral gavage

Chemical Information & Solubility

Molecular Weight 388.72 Formula

C16H20Cl3N5
CAS No. 2200214-93-1 SDF --
Smiles Cl.CC1(N)CCN(CC1)C2=CN=C(C(=N2)N)C3=CC=CC(=C3Cl)Cl
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 78 mg/mL ( (200.65 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 6 mg/mL

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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