Cat. No.: HY-100388

SHP099

76 Cited Publications

Customer Review

Based on 76 publication(s) in Google Scholar

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.

For research use only. We do not sell to patients.

Purity: 99.81%
CAS No.: 1801747-42-1
Formula: C₁₆H₁₉Cl₂N₅
Molecular Weight:352.26

Storage:

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

SHP099 Chemical Structure

CAS No.: 1801747-42-1

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (76)
Solvent & Solubility
- In Vitro
- In Vivo
Protocol
Purity & Documentation
References
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Biological Activity

Description

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]
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]
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]
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]
KYSE-520 cell line	IC₅₀	1.4 μM Compound: 1	Antiproliferative activity against human KYSE520 cells assessed as reduction in cell viability measured after 5 days by Celltiter-Glo assay Antiproliferative activity against human KYSE520 cells assessed as reduction in cell viability measured after 5 days by Celltiter-Glo assay	[PMID: 27347692]
KYSE-520 cell line	IC₅₀	1.4 μM Compound: 2; SHP099	Antiproliferative activity against human KYSE520 cells added 24 hrs after cell plating and measured on day 5 by Celltiter-Glo assay Antiproliferative activity against human KYSE520 cells added 24 hrs after cell plating and measured on day 5 by Celltiter-Glo assay	[PMID: 30688459]
KYSE-520 cell line	IC₅₀	10.8 μM Compound: SHP099	Antiproliferative activity against human KYSE-520 cells assessed as inhibition of cell growth incubated for 72 hrs by CellTiter-LumiII Luminescent assay Antiproliferative activity against human KYSE-520 cells assessed as inhibition of cell growth incubated for 72 hrs by CellTiter-LumiII Luminescent assay	[PMID: 37754066]
KYSE-520 cell line	IC₅₀	13.22 μM Compound: SHP099	Antiproliferative activity against human KYSE520 cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay Antiproliferative activity against human KYSE520 cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay	[PMID: 36097406]
KYSE-520 cell line	IC₅₀	18.2 μM Compound: 1; SHP099	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]
KYSE-520 cell line	IC₅₀	2.5 μM Compound: 10, SHP099	Antiproliferative activity against human KYSE-520 cells Antiproliferative activity against human KYSE-520 cells	[PMID: 32910655]
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.

In Vivo

After a single dose of 30 and 100 mg/kg (red and blue lines, respectively), dose-dependent exposure and modulation of the pharmacodynamic marker p-ERK is observed in the xenografts. A daily oral dose of 10 or 30 mg/kg yield 19% and 61% tumor growth inhibition, respectively. Tumor stasis is achieved at 100 mg/kg^[1].

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

Chemical Information

CAS No. 1801747-42-1
Appearance Solid
Molecular Weight 352.26
Formula C₁₆H₁₉Cl₂N₅
Color Light yellow to yellow
SMILES

NC1=NC(N2CCC(C)(N)CC2)=CN=C1C3=CC=CC(Cl)=C3Cl
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

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

Publications (76)

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Journal Impact Factor

Signal Transduct Target Ther

Elaiophylin triggers paraptosis and preferentially kills ovarian cancer drug-resistant cells by inducing MAPK hyperactivation. [Abstract]

2022 Sep 12;7(1):317. PMID: 36097006

SHP099 purchased from MedChemExpress. Usage Cited in: Signal Transduct Target Ther. 2022 Sep 12;7(1):317. [Abstract]

Assessment of indicated protein levels using western blotting in SKOV3 cells exposed to 0.5 µM elaiophylin for 24 h alone, or in combination with CHX (5 µM pretreatment for 4 h), U0126 (15 µM), SHP099 (30 µM), BAY293 (5 µM), respectively.

SHP099 purchased from MedChemExpress. Usage Cited in: Signal Transduct Target Ther. 2022 Sep 12;7(1):317. [Abstract]

SKOV3 cells were exposed to 0.5 µM elaiophylin alone for 36 h, or in combination with CHX (5 µM pretreatment for 4 h), U0126 (15 µM), SHP099 (30 µM), BAY293 (5 µM), respectively, and subject to enzymatic activity determination of CTSB.

SHP099 purchased from MedChemExpress. Usage Cited in: Signal Transduct Target Ther. 2022 Sep 12;7(1):317. [Abstract]

SHP099 (30 mg/kg/d). Representative images of tumor specimens stained with the specified antibody using immunohistochemical staining.
Cancer Discov

SHP2 Inhibition Prevents Adaptive Resistance to MEK Inhibitors in Multiple Cancer Models. [Abstract]

2018 Oct;8(10):1237-1249. PMID: 30045908

SHP099 purchased from MedChemExpress. Usage Cited in: Cancer Discov. 2018 Oct;8(10):1237-1249. [Abstract]

Immunoblots of whole cell lysates or GST-RBD-precipitated (RAS-GTP, KRASGTP and NRAS-GTP) lysates from PDAC cells treated with DMSO, SHP099 10 μM, AZD6244 1 μM, or both drugs for the times indicated.
Nat Immunol

Epithelial cells remove precancerous cells by cell competition via MHC class I-LILRB3 interaction. [Abstract]

2021 Nov;22(11):1391-1402. PMID: 34686865
Mol Cell

HSPA1A and DNAJB1 regulate NELF condensate dynamics to safeguard transcriptional recovery under heat stress. [Abstract]

2026 Feb 19;86(4):674-692.e10. PMID: 41653920
Mol Cell

A proteomic and phosphoproteomic landscape of KRAS mutant cancers identifies combination therapies. [Abstract]

2021 Oct 7;81(19):4076-4090.e8. PMID: 34375582
Cancer Res

SHP2-Mediated Inhibition of DNA Repair Contributes to cGAS-STING Activation and Chemotherapeutic Sensitivity in Colon Cancer. [Abstract]

2021 Jun 15;81(12):3215-3228. PMID: 33820798
Cancer Res

NRAS Status Determines Sensitivity to SHP2 Inhibitor Combination Therapies Targeting the RAS-MAPK Pathway in Neuroblastoma. [Abstract]

2020 Aug 15;80(16):3413-3423. PMID: 32586982
ACS Nano

Chimeric Peptide Engineered Bioregulator for Metastatic Tumor Immunotherapy through Macrophage Polarization and Phagocytosis Restoration. [Abstract]

2023 Aug 22;17(16):16056-16068. PMID: 37578051
Hepatology

Overriding Adaptive Resistance to Sorafenib Through Combination Therapy With Src Homology 2 Domain-Containing Phosphatase 2 Blockade in Hepatocellular Carcinoma. [Abstract]

2020 Jul;72(1):155-168. PMID: 31610028
Hepatology

Hepatic stellate cell-derived platelet-derived growth factor receptor-alpha-enriched extracellular vesicles promote liver fibrosis in mice through SHP2. [Abstract]

2018 Jul;68(1):333-348. PMID: 29360139

SHP099 purchased from MedChemExpress. Usage Cited in: Hepatology. 2018 Jul;68(1):333-348. [Abstract]

Primary human HSCs are treated with SHP099 for 1 hour. PDGF-BB is added and cells are cultured for 12 additional hours. Whole cell lysates and EVs are examined by WB (n=6).
Nat Commun

Mapping the landscape of genetic dependencies in chordoma. [Abstract]

2023 Apr 6;14(1):1933. PMID: 37024492
Nat Commun

Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2. [Abstract]

2018 Oct 30;9(1):4507. PMID: 30375376
Nat Commun

Mitotic regulators and the SHP2-MAPK pathway promote IR endocytosis and feedback regulation of insulin signaling. [Abstract]

2019 Apr 1;10(1):1473. PMID: 30931927

SHP099 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2019 Apr 1;10(1):1473. [Abstract]

SHP099(10 μM; 24 h) inhibits IRS1-AP2 interaction in primary hepatocytes.
Sci Transl Med

The inhibitory receptor Siglec-E controls antigen-presenting cell activation and T cell-mediated transplant rejection. [Abstract]

2025 May 7;17(797):eads2694. PMID: 40333992
Acta Pharm Sin B

Allosterically activating SHP2 by oleanolic acid inhibits STAT3-Th17 axis for ameliorating colitis. [Abstract]

2024 Jun;14(6):2598-2612. PMID: 38828149
Acta Pharm Sin B

Targeting macrophagic SHP2 for ameliorating osteoarthritis via TLR signaling. [Abstract]

2022 Jul;12(7):3073-3084. PMID: 35865095
Acta Pharm Sin B

Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics. [Abstract]

2022 Jan;12(1):149-166. PMID: 35127377
Nat Chem Biol

Plasma membrane-associated ARAF condensates fuel RAS-related cancer drug resistance. [Abstract]

2025 Aug;21(8):1226-1237. PMID: 39870764
J Clin Invest

THEMIS attenuates MASH by suppressing disease-associated hepatocyte induction and hepatocyte senescence in mice. [Abstract]

2026 May 1;136(9):e199303. PMID: 42065240
Neuro Oncol

SHP2 inhibition reduces somatotroph tumor growth in a pre-clinical model. [Abstract]

2025 Mar 6:noaf057. PMID: 40045561
Neuro Oncol

Targeting PDGFRα-activated glioblastoma through specific inhibition of SHP-2-mediated signaling. [Abstract]

2019 Nov 4;21(11):1423-1435. PMID: 31232447
Theranostics

Targeting of glioma stem-like cells with a parthenolide derivative ACT001 through inhibition of AEBP1/PI3K/AKT signaling. [Abstract]

2021 Jan 1;11(2):555-566. PMID: 33391492
Exp Mol Med

Insulin receptor endocytosis in the pathophysiology of insulin resistance. [Abstract]

2020 Jun;52(6):911-920. PMID: 32576931
J Control Release

Synergistic blockade of SHP-2 and A2AR signal pathways with targeted nanoparticles restores anti-tumor immunity of CD8+ T cells. [Abstract]

2025 May 25:384:113889. PMID: 40425093
Nano Today

2025 Apr.
MedComm (2020)

Tyrosine phosphatase SHP2 exacerbates psoriasis-like skin inflammation in mice via ERK5-dependent NETosis. [Abstract]

2022 Mar 4;3(1):e120. PMID: 35281792
J Exp Med

Ferrous iron-activatable drug conjugate achieves potent MAPK blockade in KRAS-driven tumors. [Abstract]

2022 Apr 4;219(4):e20210739. PMID: 35262628
NPJ Precis Oncol

WWP1 inhibition increases SHP2 inhibitor efficacy in colorectal cancer. [Abstract]

2024 Jul 16;8(1):144. PMID: 39014007
J Orthop Translat

Intraarticular injection of SHP2 inhibitor SHP099 promotes the repair of rabbit full-thickness cartilage defect. [Abstract]

2022 Feb 17;32:112-120. PMID: 35228993
Cell Syst

Receptor-Driven ERK Pulses Reconfigure MAPK Signaling and Enable Persistence of Drug-Adapted BRAF-Mutant Melanoma Cells. [Abstract]

2020 Nov 18;11(5):478-494.e9. PMID: 33113355
Cell Rep

Small-Molecule and CRISPR Screening Converge to Reveal Receptor Tyrosine Kinase Dependencies in Pediatric Rhabdoid Tumors. [Abstract]

2019 Aug 27;28(9):2331-2344.e8. PMID: 31461650
Br J Cancer

Drug response profiles in patient-derived cancer cells across histological subtypes of ovarian cancer: real-time therapy tailoring for a patient with low-grade serous carcinoma. [Abstract]

2023 Feb;128(4):678-690. PMID: 36476658
Neural Regen Res

Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model. [Abstract]

2025 Mar 1;20(3):858-872. PMID: 38886958
J Cell Biol

CD47 inhibits phagocytosis through Vav dephosphorylation. [Abstract]

2025 Dec 1;224(12):e202502206. PMID: 41100219
Mol Med

Assessment of the FRET-based Teen sensor to monitor ERK activation changes preceding morphological defects in a RASopathy zebrafish model and phenotypic rescue by MEK inhibitor. [Abstract]

2024 Apr 9;30(1):47. PMID: 38594640
Brain Pathol

Upregulated SHP-2 expression in the epileptogenic zone of temporal lobe epilepsy and various effects of SHP099 treatment on a pilocarpine model. [Abstract]

2020 Mar;30(2):373-385. PMID: 31398269
Cancer Cell Int

SHP2 inhibition enhances the anticancer effect of Osimertinib in EGFR T790M mutant lung adenocarcinoma by blocking CXCL8 loop mediated stemness. [Abstract]

2021 Jul 3;21(1):337. PMID: 34217295
Eur J Med Chem

Discovery of SA-8 as a potent SHP2-AUTAC degrader in cancer therapy. [Abstract]

2025 Jun 27:297:117918. PMID: 40609222
Front Immunol

SIRPα Suppresses Response to Therapeutic Antibodies by Nurse Like Cells From Chronic Lymphocytic Leukemia Patients. [Abstract]

2021 Jan 21:11:610523. PMID: 33552071
Biochem Pharmacol

An allosteric SHP2 inhibitor suppresses breast cancer-induced osteoclastogenesis and bone lysis. [Abstract]

2026 May:247:117810. PMID: 41692348
Inflamm Res

SHP2: its association and roles in systemic lupus erythematosus. [Abstract]

2023 Jul;72(7):1501-1512. PMID: 37351631
Commun Biol

Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1 dimerization and SHP-2 activation. [Abstract]

2020 Mar 17;3(1):128. PMID: 32184441
Inflammation

SHP2 Targets ITK Downstream of PD-1 to Inhibit T Cell Function. [Abstract]

2021 Aug;44(4):1529-1539. PMID: 33624224
Cancers (Basel)

Mutation of PTPN11 (Encoding SHP-2) Promotes MEK Activation and Malignant Progression in Neurofibromin-Deficient Cells in a Manner Sensitive to BRAP Mutation. [Abstract]

2022 May 12;14(10):2377. PMID: 35625983
J Biol Chem

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

2024 Jul 30:107616. PMID: 39089586
Hematol Oncol

Dependence of peripheral T-cell lymphoma on constitutively activated JAK3: Implication for JAK3 inhibition as a therapeutic approach. [Abstract]

2024 Jan;42(1):e3233. PMID: 37876297
Sci Rep

Mechanisms of synergistic suppression of ALK-positive lung cancer cell growth by the combination of ALK and SHP2 inhibitors. [Abstract]

2023 Jun 20;13(1):10041. PMID: 37339995
J Immunol Res

Hypoxia Impairs NK Cell Cytotoxicity through SHP-1-Mediated Attenuation of STAT3 and ERK Signaling Pathways. [Abstract]

2020 Jun 19;2020:4598476. PMID: 33123602
Open Biol

Targeting endogenous proteins for degradation through the affinity-directed protein missile system. [Abstract]

2017 May;7(5). pii: 170066. PMID: 28490657

SHP099 purchased from MedChemExpress. Usage Cited in: Open Biol. 2017 May;7(5). pii: 170066. [Abstract]

Comparing the effects of SHP2 degradation and allosteric inhibition on Ras/MAPK signalling. (a) Human U2OS, A549, K-562 and MDA-MB-468 cells are treated with DMSO control or 1, 5 and 10 µM SHP099 for 2 h prior to lysis. Extracts (10 µg protein) are resolved by SDS-PAGE and transferred to nitrocellulose membranes, which are subjected to western blotting with the indicated antibodies. (b) Uninfected U2OS cells (WT) or cells infected with retroviruses encoding VHL, aCS3 and VHL-aCS3 are treated wit
J Magn Reson Imaging

19Fluorine-MRI Based Longitudinal Immuno-Microenvironment-Monitoring for Pancreatic Cancer. [Abstract]

2025 Apr;61(4):1996-2008. PMID: 39189434
Exp Cell Res

CD93 promotes acute myeloid leukemia development and is a potential therapeutic target. [Abstract]

2022 Nov 15;420(2):113361. PMID: 36152731
Thromb Res

Role of SHP2 (PTPN11) in glycoprotein VI-dependent thrombus formation: Improved platelet responsiveness by the allosteric drug SHP099 in Noonan syndrome patients. [Abstract]

2023 Aug:228:105-116. PMID: 37302266
J Immunol

Non-Lyn Src Family Kinases Activate SIRPα-SHP-1 to Inhibit PI3K-Akt2 and Dampen Proinflammatory Macrophage Polarization. [Abstract]

2021 Sep 1;207(5):1419-1427. PMID: 34348974
Cancer Res Commun

SHP2 inhibition with TNO155 increases efficacy and overcomes resistance of ALK inhibitors in neuroblastoma. [Abstract]

2023 Dec 27;3(12):2608-2622. PMID: 38032104
Cancer Res Commun

Pharmacologic Inhibition of SHP2 Blocks Both PI3K and MEK Signaling in Low-epiregulin HNSCC via GAB1. [Abstract]

2022 Sep;2(9):1061-1074. PMID: 36506869
Microvasc Res

Combination mTOR and SHP2 inhibitor treatment of lymphatic malformation endothelial cells. [Abstract]

2022 Sep:143:104397. PMID: 35671835
Phytochem Anal

Danqi Pill (DQP) Attenuates OGD-Induced Injury in HUVECs via SHP2-ROS-NLRP3 Axis. [Abstract]

2026 Jan 20. PMID: 41559525
Exp Ther Med

Shp2 suppresses fat accumulation in white adipose tissue by activating Wnt/β-catenin signaling following vertical sleeve gastrectomy in obese rats with type-2 diabetes. [Abstract]

2022 Apr;23(4):302. PMID: 35340882
FEBS Open Bio

SHP2 knockdown ameliorates liver insulin resistance by activating IRS-2 phosphorylation through the AKT and ERK1/2 signaling pathways. [Abstract]

2020 Dec;10(12):2578-2587. PMID: 33012117
Biochem Biophys Res Commun

Shp2 regulates the trophoblast cell cycle progression through p53-p21 pathway modulation. [Abstract]

2025 Jun 14:776:152209. PMID: 40527180
Biochem Biophys Res Commun

Allosteric SHP2 inhibition enhances regorafenib's effectiveness in colorectal cancer treatment. [Abstract]

2024 May 21:709:149812. PMID: 38564942
Biochem Biophys Res Commun

Neonatal malnutrition impacts fibroblast growth factor 21-induced neuron neurite outgrowth and growth hormone-releasing hormone secretion in neonatal mouse brain. [Abstract]

2023 Oct 8:676:121-131. PMID: 37506473
J Histochem Cytochem

Development of an ALK-positive Non-Small-Cell Lung Cancer in Vitro Tumor 3D Culture Model for Therapeutic Screening. [Abstract]

2025 Jan-Feb;73(1-2):63-79. PMID: 39991927
Res Sq

2026 Feb 17.
bioRxiv

Synergistic effects of deleting the tyrosine phosphatases Shp1 and Shp2 on megakaryopoiesis and thrombopoiesis in mice. [Abstract]

2025 Oct 26:2025.10.24.684367. PMID: 41279089
bioRxiv

Post-Translational Modifications Remodel Proteome-Wide Ligandability. [Abstract]

2025 Aug 2:2025.07.31.667978. PMID: 40766426
bioRxiv

2024 November 06.
bioRxiv

2024 Feb 5.
Patent

US20220380385A1.
Research Square Preprint

2021 Apr.
Research Square Preprint

2021 Mar.
Ann Transl Med

Uric acid preconditioning alleviated doxorubicin induced JNK activation and Cx43 phosphorylation associated cardiotoxicity via activation of AMPK-SHP2 signaling pathway. [Abstract]

2020 Dec;8(23):1570. PMID: 33437769
Patent

US20200330595A1.
SSRN

2020 May.
bioRxiv

2019 Sep.
Patent

US20190231805A1.

Solvent & Solubility

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)

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

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

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.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

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

Stock Solution Working Solution

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.

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.

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

Working 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

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protocol

Kinase Assay^[1]

The inhibition of SHP2 from the tested compounds (SHP099) concentrations varying from 0.003-100 μM is monitored using an assay in which 0.5 nM of SHP2 is incubated with of 0.5 μM of peptide IRS1_pY1172(dPEG8)pY1222. After 30-60 minutes incubation at the surrogate substrate, DiFMUP is added to the reaction and incubated at 25 °C for 30 minutes. The reaction is then quenched by the addition of 5 μL of a 160 μM solution of bpV(Phen). The fluorescence signal is monitored using a microplate reader using excitation and emission wavelengths of 340 nm and 450 nm, respectively^[1].

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

Cell Assay^[1]

Cells are plated onto 96-well plates in 100 μL medium. SHP099 with various concentrations (1.25, 2.5, 5, 10, 20 μM) are added 24 h after cell plating. At day 5, 50 μL Celltiter-Glo reagent is added, and the luminescent signal is determined^[1].

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

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (279 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 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)

References

[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]

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	2.8388 mL	14.1941 mL	28.3881 mL	70.9703 mL
	5 mM	0.5678 mL	2.8388 mL	5.6776 mL	14.1941 mL
	10 mM	0.2839 mL	1.4194 mL	2.8388 mL	7.0970 mL
	15 mM	0.1893 mL	0.9463 mL	1.8925 mL	4.7314 mL
	20 mM	0.1419 mL	0.7097 mL	1.4194 mL	3.5485 mL
	25 mM	0.1136 mL	0.5678 mL	1.1355 mL	2.8388 mL
	30 mM	0.0946 mL	0.4731 mL	0.9463 mL	2.3657 mL

Keywords

Product Name:
Cat. No.:
Quantity:
MCE Japan Authorized Agent:

Product Name:
CAS No.:
Species:
Purity:
Quantity:

SHP099

Kinase Inhibitor Library

Metabolism/Protease Compound Library

Protein Tyrosine Kinase Compound Library

Anti-Cancer Compound Library

Orally Active Compound Library

Phosphatase Inhibitor Library

Human Metabolite Library

Metabolic Enzyme Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Protein Kinase Compound Library

High-Throughput Bioactive Compound Library

Mass Spectrometry Human Metabolite Library

Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) SHP099

Biological Activity

Chemical Information

Publications (76)

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

SHP099

Kinase Inhibitor Library

Metabolism/Protease Compound Library

Protein Tyrosine Kinase Compound Library

Anti-Cancer Compound Library

Orally Active Compound Library

Phosphatase Inhibitor Library

Human Metabolite Library

Metabolic Enzyme Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Protein Kinase Compound Library

High-Throughput Bioactive Compound Library

Mass Spectrometry Human Metabolite Library

Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) SHP099

Biological Activity

Chemical Information

Publications (76)

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

SHP099 Related Classifications

Cat. No.: HY-100388