SHP099 free base | CAS#1801747-42-1 | SHP2 inhibitor

MedKoo Cat#: 407376 | Name: SHP099 free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

SHP099 is a potent, selective, orally bioavailable, and efficacious SHP2 inhibitor with IC50 =0.07 μM and p-ERK modulation in cells IC50 = 0.250 μM. SHP099 exhibits dose-dependent pathway inhibition and antitumor activity in xenograft models. SHP2 is a nonreceptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also purportedly plays an important role in the programmed cell death pathway (PD-1/PD-L1).

Chemical Structure

SHP099 free base

CAS#1801747-42-1 (free base)

Theoretical Analysis

MedKoo Cat#: 407376

Name: SHP099 free base

CAS#: 1801747-42-1 (free base)

Chemical Formula: C16H19Cl2N5

Exact Mass: 351.1018

Molecular Weight: 352.26

Elemental Analysis: C, 54.55; H, 5.44; Cl, 20.13; N, 19.88

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,650.00	Ready to ship
2g	USD 3,950.00	Ready to ship
5g	USD 6,250.00	2 weeks

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Related CAS #

1801747-42-1 (free base) 2200214-93-1 (HCl)

Synonym

SHP099; SHP-099; SHP 099.

IUPAC/Chemical Name

6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine

InChi Key

YGUFCDOEKKVKJK-UHFFFAOYSA-N

InChi Code

InChI=1S/C16H19Cl2N5/c1-16(20)5-7-23(8-6-16)12-9-21-14(15(19)22-12)10-3-2-4-11(17)13(10)18/h2-4,9H,5-8,20H2,1H3,(H2,19,22)

SMILES Code

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

Appearance

Solid powder

Purity

>97% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#Y8X11M28

QC Data

View QC data: current batch, Lot#Y8X22M28

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SHP099 is an SHP2 inhibitor with an IC50 of 70 nM.

In vitro activity:

Targeting cells harboring SHP2 p.Glu76Gln and p.Glu76Ala with SHP099 may be useful in the treatment of canine histiocytic sarcoma (HS). Of five of canine HS cell lines expressing SHP2, SHP099 potently suppressed the growth of two of the mutant cell lines (SHP2 p.Glu76Gln or p.Glu76Ala) but not that of the other three cell lines. SHP099 suppressed ERK activation in the cell line harbouring the SHP2 p.Glu76Ala mutation. Reference: Vet Comp Oncol. 2020 Jun;18(2):161-168. https://pubmed.ncbi.nlm.nih.gov/31339650/

In vivo activity:

SHP099 has potential for acute lung injury (ALI) treatment. Giving SHP099 to mice with ALI and sepsis relieved ALI and significantly increased animal survival. Reference: Inflammation. 2023 Jun;46(3):975-986. https://pubmed.ncbi.nlm.nih.gov/36732395/

	Solvent	mg/mL	mM
Solubility
	DMSO	21.0	34.07
	Water	1.0	2.84

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 352.26 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Tani H, Kurita S, Miyamoto R, Ochiai K, Tamura K, Bonkobara M. Canine histiocytic sarcoma cell lines with SHP2 p.Glu76Gln or p.Glu76Ala mutations are sensitive to allosteric SHP2 inhibitor SHP099. Vet Comp Oncol. 2020 Jun;18(2):161-168. doi: 10.1111/vco.12524. Epub 2019 Aug 19. PMID: 31339650. 2. Hao HX, Wang H, Liu C, Kovats S, Velazquez R, Lu H, Pant B, Shirley M, Meyer MJ, Pu M, Lim J, Fleming M, Alexander L, Farsidjani A, LaMarche MJ, Moody S, Silver SJ, Caponigro G, Stuart DD, Abrams TJ, Hammerman PS, Williams J, Engelman JA, Goldoni S, Mohseni M. Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers. Mol Cancer Ther. 2019 Dec;18(12):2368-2380. doi: 10.1158/1535-7163.MCT-19-0170. Epub 2019 Aug 22. PMID: 31439712. 3. Ye S, Zuo B, Xu L, Wu Y, Luo R, Ma L, Yao W, Chen L, Liang G, Zhang Y. Inhibition of SHP2 by the Small Molecule Drug SHP099 Prevents Lipopolysaccharide-Induced Acute Lung Injury in Mice. Inflammation. 2023 Jun;46(3):975-986. doi: 10.1007/s10753-023-01784-8. Epub 2023 Feb 3. PMID: 36732395. 4. Sun Z, Xu X, Lv Z, Li J, Shi T, Sun H, Sun K, Tan G, Yan W, Yang YX, Wu R, Xu J, Guo H, Jiang Q, Shi D. Intraarticular injection of SHP2 inhibitor SHP099 promotes the repair of rabbit full-thickness cartilage defect. J Orthop Translat. 2022 Feb 17;32:112-120. doi: 10.1016/j.jot.2022.01.001. PMID: 35228993; PMCID: PMC8857578.

In vitro protocol:

In vivo protocol:

1. Ye S, Zuo B, Xu L, Wu Y, Luo R, Ma L, Yao W, Chen L, Liang G, Zhang Y. Inhibition of SHP2 by the Small Molecule Drug SHP099 Prevents Lipopolysaccharide-Induced Acute Lung Injury in Mice. Inflammation. 2023 Jun;46(3):975-986. doi: 10.1007/s10753-023-01784-8. Epub 2023 Feb 3. PMID: 36732395. 2. Sun Z, Xu X, Lv Z, Li J, Shi T, Sun H, Sun K, Tan G, Yan W, Yang YX, Wu R, Xu J, Guo H, Jiang Q, Shi D. Intraarticular injection of SHP2 inhibitor SHP099 promotes the repair of rabbit full-thickness cartilage defect. J Orthop Translat. 2022 Feb 17;32:112-120. doi: 10.1016/j.jot.2022.01.001. PMID: 35228993; PMCID: PMC8857578.

1: Xi R, Cao Y, Fu N, Sheng Y, Yu J, Li L, Zhang G, Wang F. Allosteric inhibition of the tyrosine phosphatase SHP2 enhances the anti-tumor immunity of interferon α through induction of caspase-1-mediated pyroptosis in renal cancer. Int Immunopharmacol. 2024 Oct 27;143(Pt 2):113498. doi: 10.1016/j.intimp.2024.113498. Epub ahead of print. PMID: 39467353. 2: Pan J, Qu J, Fang W, Zhao L, Zheng W, Zhai L, Tan M, Xu Q, Du Q, Lv W, Sun Y. SHP2-Triggered Endothelial Cell Activation Fuels Estradiol-Independent Endometrial Sterile Inflammation. Adv Sci (Weinh). 2024 Nov;11(41):e2403038. doi: 10.1002/advs.202403038. Epub 2024 Sep 5. PMID: 39234819; PMCID: PMC11538683. 3: Reichardt W, Gewalt T, Hafner P, Keller SJ, Chen X, Alrawashdeh A, Li Y, Besson S, Fichtner-Feigl S, von Elverfeldt D, Jumaa H, Ruess DA. 19Fluorine-MRI Based Longitudinal Immuno-Microenvironment-Monitoring for Pancreatic Cancer. J Magn Reson Imaging. 2024 Aug 27. doi: 10.1002/jmri.29589. Epub ahead of print. PMID: 39189434. 4: Zhang L, Ma W, Chen Y, Chen Z, Wang F, Xu Y. Design, synthesis, and biological evaluation of Pyrido[1,2-a]pyrimidin-4-one derivatives as novel allosteric SHP2 inhibitors. Bioorg Chem. 2024 Oct;151:107661. doi: 10.1016/j.bioorg.2024.107661. Epub 2024 Jul 17. PMID: 39067422. 5: Zhu C, Zhao H, Yang W, Chen K, Liu X, Yu Y, Li R, Tan R, Yu Z. Design, Synthesis and Antitumor Activity of a Novel Class of SHP2 Allosteric Inhibitors with a Furanyl Amide-Based Scaffold. J Med Chem. 2024 Aug 8;67(15):13305-13323. doi: 10.1021/acs.jmedchem.4c01217. Epub 2024 Jul 27. PMID: 39066713. 6: Singh P, Kumar V, Lee KW, Hong JC. Discovery of Novel Allosteric SHP2 Inhibitor Using Pharmacophore-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation, and Principal Component Analysis. Pharmaceuticals (Basel). 2024 Jul 12;17(7):935. doi: 10.3390/ph17070935. PMID: 39065785; PMCID: PMC11280062. 7: Wang M, Yu K, Fu W, Yang L. The combination of SHP099 inhibits the malignant biological behavior of L-OHP/5-FU-resistant colorectal cancer cells by regulating energy metabolism reprogramming. Biochem Biophys Res Commun. 2024 Oct 8;728:150262. doi: 10.1016/j.bbrc.2024.150262. Epub 2024 Jun 28. PMID: 38959530. 8: Gong Y, Gao W, Zhang J, Dong X, Zhu D, Ma G. Engineering nanoparticles- enabled tumor-associated macrophages repolarization and phagocytosis restoration for enhanced cancer immunotherapy. J Nanobiotechnology. 2024 Jun 18;22(1):341. doi: 10.1186/s12951-024-02622-1. PMID: 38890636; PMCID: PMC11184870. 9: Petrocchi A, Ciammaichella A. A patent review of SHP2 allosteric inhibitors (2018-present). Expert Opin Ther Pat. 2024 May;34(5):383-396. doi: 10.1080/13543776.2024.2365410. Epub 2024 Jun 13. PMID: 38842843. 10: Hu J, Liu W, Zou Y, Jiao C, Zhu J, Xu Q, Zou J, Sun Y, Guo W. Allosterically activating SHP2 by oleanolic acid inhibits STAT3-Th17 axis for ameliorating colitis. Acta Pharm Sin B. 2024 Jun;14(6):2598-2612. doi: 10.1016/j.apsb.2024.03.017. Epub 2024 Mar 18. PMID: 38828149; PMCID: PMC11143531. 11: Yang L, Zhao H, Yuan F, Chen M, Ma N, Yin Z, Liu H, Guo Y. Computational study on the binding mechanism of allosteric drug TNO155 inhibiting SHP2E76A. Mol Divers. 2024 May 28. doi: 10.1007/s11030-024-10881-1. Epub ahead of print. PMID: 38807000. 12: Hsu MF, Koike S, Chen CS, Najjar SM, Meng TC, Haj FG. Pharmacological inhibition of the Src homology phosphatase 2 confers partial protection in a mouse model of alcohol-associated liver disease. Biomed Pharmacother. 2024 Jun;175:116590. doi: 10.1016/j.biopha.2024.116590. Epub 2024 Apr 22. PMID: 38653109. 13: Wang P, Han Y, Pan W, Du J, Zuo D, Ba Y, Zhang H. Tyrosine phosphatase SHP2 aggravates tumor progression and glycolysis by dephosphorylating PKM2 in gastric cancer. MedComm (2020). 2024 Apr 4;5(4):e527. doi: 10.1002/mco2.527. PMID: 38576457; PMCID: PMC10993348. 14: Han X, Wang W, Wang R, Zhang W, Zhu L, Xu Q, Guo W, Gu Y. Allosteric SHP2 inhibition enhances regorafenib's effectiveness in colorectal cancer treatment. Biochem Biophys Res Commun. 2024 May 21;709:149812. doi: 10.1016/j.bbrc.2024.149812. Epub 2024 Mar 26. PMID: 38564942. 15: Han X, Wei J, Zheng R, Tu Y, Wang M, Chen L, Xu Z, Zheng L, Zheng C, Shi Q, Ying H, Liang G. Macrophage SHP2 Deficiency Alleviates Diabetic Nephropathy via Suppression of MAPK/NF-κB- Dependent Inflammation. Diabetes. 2024 May 1;73(5):780-796. doi: 10.2337/db23-0700. PMID: 38394639. 16: Li T, Xu B, Li W, Cheng X, Tantai W, Zheng H, Zhao L, Li N, Han C. Allosteric inhibitor of SHP2 enhances macrophage endocytosis and bacteria elimination by increasing caveolae activation and protects against bacterial sepsis. Pharmacol Res. 2024 Mar;201:107096. doi: 10.1016/j.phrs.2024.107096. Epub 2024 Feb 4. PMID: 38320736. 17: Du T, Hu X, Hou Z, Wang W, You S, Wang M, Ji M, Xue N, Chen X. Re-expression of epigenetically silenced PTPRR by histone acetylation sensitizes RAS-mutant lung adenocarcinoma to SHP2 inhibition. Cell Mol Life Sci. 2024 Jan 28;81(1):64. doi: 10.1007/s00018-023-05034-w. PMID: 38280930; PMCID: PMC11073200. 18: Ying K, Xin W, Xu Y, Lv D, Zhu H, Li Y, Xu W, Yan C, Li Y, Cheng H, Chen E, Ma G, Zhang X, Ke Y. NanoSHP099-Targeted SHP2 Inhibition Boosts Ly6Clow Monocytes/Macrophages Differentiation to Accelerate Thrombolysis. Adv Sci (Weinh). 2024 Apr;11(13):e2308166. doi: 10.1002/advs.202308166. Epub 2024 Jan 21. PMID: 38247197; PMCID: PMC10987109. 19: Mitra R, Kumar S, Ayyannan SR. Identification of new small molecule allosteric SHP2 inhibitor through pharmacophore-based virtual screening, molecular docking, molecular dynamics simulation studies, synthesis and in vitro evaluation. J Biomol Struct Dyn. 2023 Dec 14:1-20. doi: 10.1080/07391102.2023.2291733. Epub ahead of print. PMID: 38095360. 20: Wu C, Zheng P, Ma L, Xu C, Hu L, Yang Z, Fei F, Shen Z, Zhang X, Wu Z, Cheng H, Mao W, Ke Y. Protein Tyrosine Phosphatase SHP2 in Macrophages Acts as an Antiatherosclerotic Regulator in Mice. Arterioscler Thromb Vasc Biol. 2024 Jan;44(1):202-217. doi: 10.1161/ATVBAHA.123.319663. Epub 2023 Nov 9. PMID: 37942607.