SHP099 HCl

Catalog No.S8278

For research use only.

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

CAS No. 2200214-93-1

Selleck's SHP099 HCl has been cited by 35 publications

Purity & Quality Control

Choose Selective phosphatase Inhibitors

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

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 Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MGH049-1A MknjSpVv[3Srb36gZZN{[Xl? NVzk[IptPSEQvF2= MXyxOEBl[Xm| MWTBd{BiKHOrbnfs[UBi\2WwdDygV2hRODl7IHjh[EBucW6rbXHsJIVn\mWldDDvckBk\WyuIIDyc4xq\mW{YYTpc44> NX25NFhDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm1NFUxOzNpPkK5OVA2ODN|PD;hQi=>
MGH073-2B MULGeY5kfGmxbjDhd5NigQ>? MkixOUDPxE1? M4SyOVE1KGSjeYO= MnW3RZMh[SC|aX7ncIUh[WenboSsJHNJWDB7OTDoZYQhdWmwaX3hcEBm\m[nY4Sgc44h[2WubDDwdo9tcW[ncnH0bY9v Mm\lQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl3MEWwN|MoRjJ7NUC1NFM{RC:jPh?=
MGH065-1B MXjGeY5kfGmxbjDhd5NigQ>? NYjJR2k6PSEQvF2= NXvI[m9TOTRiZHH5dy=> NHnJOHBCeyCjIIPpcodt\SCjZ3XueEwhW0iSMEm5JIhi\CCvaX7pcYFtKGWoZnXjeEBwdiClZXzsJJBzd2yrZnXyZZRqd25? NW[2[o9kRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm1NFUxOzNpPkK5OVA2ODN|PD;hQi=>
MGH045-2A NIXLeYdHfW6ldHnvckBie3OjeR?= MUS1JO69VQ>? Moi1NVQh\GG7cx?= MX7Bd{BiKHOrbnfs[UBi\2WwdDygV2hRODl7IHjh[EBucW6rbXHsJIVn\mWldDDvckBk\WyuIIDyc4xq\mW{YYTpc44> NXvjVGhjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm1NFUxOzNpPkK5OVA2ODN|PD;hQi=>
U2OS cells M3f3VGZ2dmO2aX;uJIF{e2G7 NEHMZpcxNCBzLDCzMEA3NCBzMjygNlUtKDVyIN88US=> NEjEUlNUUFByOUmgdoVlfWOnczDwSZJsKGyndnXsd{BqdiC5aXzkMZR6eGViVULPV{Bk\Wyucz6= NGnGd2Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEO3OVM5QCd-M{CzO|U{QDh:L3G+
KYSE-520 Mn7VVJJwdGmoZYLheIlwdiCjc4PhfS=> MV:1JIRigXN? MXjpcohq[mm2aX;uJI9nKGOnbHygdJJwdGmoZYLheIlwdiC5aYToJIFvKEmFNUCgc4YhOS52IN88US=> NH74W|c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{O0O|Y6Oid-MkezOFc3QTJ:L3G+
MOLM14 M37ifGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 MX6zJIRigXN? NFL4OZNCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3PUG0yPCClZXzsd{Bi\nSncjCzJIRigXNiYomgR4VtdFSrdHXyMWdtdyCudX3pcoV{[2WwY3WgZZN{[XluIFnDOVAhRSByLkmg{txONg>? NXm5eG9ORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmwPFkzPTdpPkK5NFg6OjV5PD;hQi=>
Assay
Methods Test Index PMID
Western blot pERK / Bcl-xL / p85 PARP ; pMEK / MEK / pERK / Erk ; EGFR / pEGFR / GAB1 / pSHP2 / GRB2 / SOS1 29568093 30605687
Growth inhibition assay Cell viability 29568093
Immunofluorescence insulin receptor 30931927
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].

Protocol (from reference)

Cell Research:

[1]

  • 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.

Animal Research:

[1]

  • Animal Models: Nude mice (Tumor Xenograft)
  • Dosages: 10, 30, or 100 mg/kg qd
  • Administration: by oral gavage

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 388.72
Formula

C16H20Cl3N5

CAS No. 2200214-93-1
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles Cl.CC1(N)CCN(CC1)C2=CN=C(C(=N2)N)C3=CC=CC(=C3Cl)Cl

In vivo Formulation Calculator (Clear solution)

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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.

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Molarity Calculator

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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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