SHP099 HCl: SHP2 Inhibitor FAQs for Researchers

SHP099 HCl is a potent, selective allosteric inhibitor of the SHP2 phosphatase (encoded by PTPN11) widely used in research to dissect RAS-MAPK oncogenic signaling.

Product Name

SHP099 HCl

Catalog SKU

S413959

Selleck Reference Number

S8278

Target

SHP2 (PTPN11) phosphatase

Inhibition Mechanism

Allosteric (locks SHP2 in closed, inactive conformation)

Primary Research Application

RAS-MAPK pathway inhibition, oncology, signal transduction

What Is SHP099 HCl and How Does It Work?

SHP099 HCl is the hydrochloride salt form of SHP099, a first-in-class small-molecule allosteric inhibitor of SHP2, the non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene. Unlike competitive active-site inhibitors, SHP099 stabilizes SHP2 in its autoinhibited, closed conformation by binding at the interface of the N-SH2, C-SH2, and PTP domains. This prevents the conformational opening required for substrate engagement, thereby blocking SHP2 catalytic activity without directly occupying the phosphatase active site.

SHP2 acts as a key node downstream of multiple receptor tyrosine kinases (RTKs) and upstream of the RAS-MAPK and PI3K-AKT cascades. By inhibiting SHP2, SHP099 HCl suppresses oncogenic RAS signaling, making it a valuable tool compound for studying RTK-driven proliferation and survival in cancer cell models.

Recommended Storage and Handling of SHP099 HCl

As a hydrochloride salt, SHP099 HCl generally exhibits improved aqueous solubility compared with the free base. For long-term storage, keep the solid compound at −20 °C in a tightly sealed, desiccated container protected from light and moisture. Avoid repeated freeze-thaw cycles of stock solutions, as these can degrade the compound over time.

For preparation of working solutions, dimethyl sulfoxide (DMSO) is the most commonly used solvent for preparing concentrated stocks. The final DMSO concentration in cell-based assays should be kept ≤0.1 % (v/v) to minimize cytotoxic effects. Always warm the vial to room temperature before opening to prevent condensation. Consult the product-specific Certificate of Analysis (CoA) for lot-specific solubility data and purity confirmation before use.

Note: Specific solubility values and recommended storage temperatures should be verified against the CoA supplied with SKU S413959, as these parameters are lot-dependent.

Experimental Applications and Research Context

SHP099 HCl is primarily employed as a pharmacological tool to probe SHP2 biology in the following research contexts:

• Oncology models: Investigating SHP2's role in RTK-amplified or RAS-mutant cancers, including lung, breast, and hematological malignancies.
• Combination studies: Evaluating synergy with EGFR, MEK, or KRAS inhibitors to overcome adaptive resistance.
• Signaling pathway dissection: Using SHP099 HCl as a reference inhibitor to confirm SHP2 dependency in RAS-MAPK or PI3K-AKT activation assays.
• Structural biology support: Serving as a reference compound in co-crystallization or biophysical binding studies of SHP2 allosteric sites.

Researchers should validate target engagement using appropriate readouts such as p-ERK1/2 or p-AKT immunoblotting alongside SHP2 phosphatase activity assays when characterizing inhibition in their specific cellular system.

Purity, Quality Control, and Regulatory Considerations

Aladdin Scientific's SHP099 HCl (SKU S413959) is supplied as a research-grade reagent intended exclusively for in vitro and preclinical in vivo laboratory research. It is not approved for human therapeutic use, veterinary use, or any clinical application. Each lot is subject to quality control testing; consult the CoA for purity data (typically assessed by HPLC) and structural confirmation (NMR or MS).

When ordering, procurement teams should request the CoA and Safety Data Sheet (SDS) to ensure compliance with institutional chemical inventory and safety requirements. The compound contains a hydrochloride salt moiety; handle according to standard laboratory chemical safety protocols, including appropriate PPE (gloves, eye protection, lab coat) and disposal in accordance with local regulations.

Frequently asked questions

What is the selectivity profile of SHP099 HCl for SHP2 over SHP1?

SHP099 was reported to be selective for SHP2 over SHP1 in published literature, exploiting differences in the allosteric tunnel between the two homologous phosphatases. However, researchers should consult the primary literature and validate selectivity in their own experimental system, as cross-reactivity at high concentrations cannot be excluded without confirmatory profiling data.

In which solvent should I dissolve SHP099 HCl for cell-based assays?

DMSO is the recommended solvent for preparing concentrated stock solutions of SHP099 HCl. Dilute the DMSO stock into aqueous cell culture medium immediately before use, and ensure the final DMSO concentration does not exceed 0.1 % (v/v) in assay wells to avoid solvent-related cytotoxicity. Always include a vehicle control (equivalent DMSO concentration) in your experimental design.

Is SHP099 HCl (SKU S413959) the same compound as Selleck S8278?

Yes. The source material for Aladdin Scientific's SHP099 HCl (SKU S413959) references Selleck Number S8278, indicating it is the same chemical entity — SHP099 hydrochloride. Researchers cross-referencing literature that cites S8278 can use SKU S413959 as the equivalent reagent, subject to verification of purity and lot specifications via the CoA.

What positive and negative controls should I use when testing SHP099 HCl in a phosphatase activity assay?

For a SHP2 phosphatase activity assay, use recombinant active SHP2 protein with a suitable phosphopeptide or pNPP substrate as the positive enzymatic control, and an enzyme-free blank as the negative control. Include a vehicle (DMSO) control at the same final concentration used in test wells. A known SHP2 inhibitor from an independent chemotype can serve as an additional reference standard to benchmark assay performance.

Can SHP099 HCl be used in animal (in vivo) studies?

SHP099 HCl has been described in preclinical in vivo studies in the published literature, typically formulated in aqueous vehicles for oral or intraperitoneal dosing in rodent tumor models. However, Aladdin Scientific supplies this compound strictly as a research reagent, and users are responsible for independently establishing appropriate in vivo dosing formulations, IACUC approval, and compliance with all institutional and regulatory requirements.

References

1. Chen YN, et al. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature. 2016.
2. Selleck Chemicals. SHP099 HCl Product Page, Catalog No. S8278.

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.