SHP099 monohydrochloride

Name: SHP099 monohydrochloride
Brand: MedChemExpress
SKU: HY-100388A
Rating: 5.0 (64 reviews)

Cat. No.: HY-100388A Purity: 99.87%: FAQs
Data Sheet SDS COA Handling Instructions

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SHP099 hydrochloride is a potent, selective and orally available SHP2 inhibitor with an IC₅₀ of 70 nM.

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

SHP099 monohydrochloride Chemical Structure

CAS No. : 2200214-93-1

Size	Price	Stock	Quantity

Free Sample (0.1 - 0.5 mg)		Apply Now
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 79	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 79	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 92	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 132	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 317	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 581	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Customer Review

Based on 64 publication(s) in Google Scholar

Other Forms of SHP099 monohydrochloride:

SHP099 In-stock
SHP099 hydrochloride Get quote

60 Publications Citing Use of MCE SHP099 monohydrochloride

: SHP099 monohydrochloride 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.

: SHP099 monohydrochloride purchased from MedChemExpress. Usage Cited in: Nat Commun. 2019 Apr 1;10(1):1473. [Abstract]; SHP099 inhibits IRS1-AP2 interaction in primary hepatocytes.

: SHP099 monohydrochloride 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).

: SHP099 monohydrochloride 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

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Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

SHP099 hydrochloride is a potent, selective and orally available SHP2 inhibitor with an IC₅₀ of 70 nM^[1].

IC₅₀ & Target

IC50: 70 nM (SHP2)^[1]

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 doses of 30 and 100 mg/kg , 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.

Molecular Weight

388.72

Formula

C₁₆H₂₀Cl₃N₅

CAS No.

2200214-93-1

Appearance

Solid

SMILES

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility

In Vitro:

DMSO : 4.1 mg/mL (10.55 mM; Need ultrasonic and warming; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : ≥ 2.5 mg/mL (6.43 mM)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.5725 mL	12.8627 mL	25.7255 mL
5 mM	0.5145 mL	2.5725 mL	5.1451 mL
10 mM	0.2573 mL	1.2863 mL	2.5725 mL

View the Complete Stock Solution Preparation Table

* 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 (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Molarity Calculator
Dilution Calculator

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

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

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

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: ≥ 2.5 mg/mL (6.43 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline 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: 50% PEG300 50% Saline
Solubility: 20 mg/mL (51.45 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

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

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

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).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 99.92%

Select Batch:

Data Sheet (277 KB) SDS (393 KB)

COA (250 KB) LCMS (149 KB)

Handling Instructions (2659 KB)

References

[1]. Garcia Fortanet J, et al. Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor. J Med Chem. 2016 Sep 8;59(17):7773-82. [Content Brief]

[2]. 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]

[3]. Carmine Fedele, et al. SHP2 Inhibition Abrogates MEK inhibitor Resistance in Multiple Cancer Models. bioRxiv. April 25, 2018.

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]. 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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Garcia Fortanet J, et al. Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor. J Med Chem. 2016 Sep 8;59(17):7773-82. [Content Brief] [2]. 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] [3]. Carmine Fedele, et al. SHP2 Inhibition Abrogates MEK inhibitor Resistance in Multiple Cancer Models. bioRxiv. April 25, 2018.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

H₂O / DMSO	1 mM	2.5725 mL	12.8627 mL	25.7255 mL	64.3136 mL
H₂O / DMSO	5 mM	0.5145 mL	2.5725 mL	5.1451 mL	12.8627 mL
DMSO	10 mM	0.2573 mL	1.2863 mL	2.5725 mL	6.4314 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.