SHP099 hydrochloride | CAS#2200214-93-1 | SHP2 inhibitor

MedKoo Cat#: 406794 | Name: SHP099 HCl

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). Because it is an oncoprotein associated with multiple cancer-related diseases, as well as a potential immunomodulator, controlling SHP2 activity is of significant therapeutic interest.

Chemical Structure

SHP099 HCl

CAS#2200214-93-1 (HCl)

Theoretical Analysis

MedKoo Cat#: 406794

Name: SHP099 HCl

CAS#: 2200214-93-1 (HCl)

Chemical Formula: C16H20Cl3N5

Exact Mass: 0.0000

Molecular Weight: 388.72

Elemental Analysis: C, 49.44; H, 5.19; Cl, 27.36; N, 18.02

Price and Availability

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

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Related CAS #

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

Synonym

SHP099; SHP-099; SHP 099. SHP-099 hydrochloride, SHP-099 HCl.

IUPAC/Chemical Name

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

InChi Key

KHQHYRFUYAXWOQ-UHFFFAOYSA-N

InChi Code

InChI=1S/C16H19Cl2N5.ClH/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);1H

SMILES Code

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

Appearance

Yellow solid powder

Purity

>98% (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

Related CAS# CAS#1801747-42-1 ( SHP099 free base); CAS#1801747-11-4 ( SHP099 HCl)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#YXM61109

QC Data

View QC data: current batch, Lot#YXM61109

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	41.1	105.60
	Methanol	25.0	64.31
	Water	4.3	10.93

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 388.72 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: LaRochelle JR, Fodor M, Vemulapalli V, Mohseni M, Wang P, Stams T, LaMarche MJ, Chopra R, Acker MG, Blacklow SC. Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition. Nat Commun. 2018 Oct 30;9(1):4508. doi: 10.1038/s41467-018-06823-9. PubMed PMID: 30375388; PubMed Central PMCID: PMC6207684. 2: Pádua RAP, Sun Y, Marko I, Pitsawong W, Stiller JB, Otten R, Kern D. Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2. Nat Commun. 2018 Oct 30;9(1):4507. doi: 10.1038/s41467-018-06814-w. PubMed PMID: 30375376; PubMed Central PMCID: PMC6207724. 3: Hill KS, Roberts ER, Wang X, Marin E, Park TD, Son S, Ren Y, Fang B, Yoder S, Kim S, Wan L, Sarnaik AA, Koomen JM, Messina JL, Teer JK, Kim Y, Wu J, Chalfant CE, Kim M. PTPN11 plays oncogenic roles and is a therapeutic target for BRAF wild-type melanomas. Mol Cancer Res. 2018 Oct 24. pii: molcanres.0777.2018. doi: 10.1158/1541-7786.MCR-18-0777. [Epub ahead of print] PubMed PMID: 30355677. 4: Fedele C, Ran H, Diskin B, Wei W, Jen J, Geer MJ, Araki K, Ozerdem U, Simeone DM, Miller G, Neel BG, Tang KH. SHP2 Inhibition Prevents Adaptive Resistance to MEK Inhibitors in Multiple Cancer Models. Cancer Discov. 2018 Oct;8(10):1237-1249. doi: 10.1158/2159-8290.CD-18-0444. Epub 2018 Jul 25. PubMed PMID: 30045908; PubMed Central PMCID: PMC6170706. 5: Sun X, Ren Y, Gunawan S, Teng P, Chen Z, Lawrence HR, Cai J, Lawrence NJ, Wu J. Selective inhibition of leukemia-associated SHP2(E69K) mutant by the allosteric SHP2 inhibitor SHP099. Leukemia. 2018 May;32(5):1246-1249. doi: 10.1038/s41375-018-0020-5. Epub 2018 Jan 30. PubMed PMID: 29568093; PubMed Central PMCID: PMC6166654. 6: Batth TS, Papetti M, Pfeiffer A, Tollenaere MAX, Francavilla C, Olsen JV. Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling. Cell Rep. 2018 Mar 6;22(10):2784-2796. doi: 10.1016/j.celrep.2018.02.038. PubMed PMID: 29514104. 7: Dardaei L, Wang HQ, Singh M, Fordjour P, Shaw KX, Yoda S, Kerr G, Yu K, Liang J, Cao Y, Chen Y, Lawrence MS, Langenbucher A, Gainor JF, Friboulet L, Dagogo-Jack I, Myers DT, Labrot E, Ruddy D, Parks M, Lee D, DiCecca RH, Moody S, Hao H, Mohseni M, LaMarche M, Williams J, Hoffmaster K, Caponigro G, Shaw AT, Hata AN, Benes CH, Li F, Engelman JA. SHP2 inhibition restores sensitivity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors. Nat Med. 2018 May;24(4):512-517. doi: 10.1038/nm.4497. Epub 2018 Mar 5. PubMed PMID: 29505033. 8: Jin WY, Ma Y, Li WY, Li HL, Wang RL. Scaffold-based novel SHP2 allosteric inhibitors design using Receptor-Ligand pharmacophore model, virtual screening and molecular dynamics. Comput Biol Chem. 2018 Apr;73:179-188. doi: 10.1016/j.compbiolchem.2018.02.004. Epub 2018 Feb 8. PubMed PMID: 29494926. 9: Kostallari E, Hirsova P, Prasnicka A, Verma VK, Yaqoob U, Wongjarupong N, Roberts LR, Shah VH. Hepatic stellate cell-derived platelet-derived growth factor receptor-alpha-enriched extracellular vesicles promote liver fibrosis in mice through SHP2. Hepatology. 2018 Jul;68(1):333-348. doi: 10.1002/hep.29803. Epub 2018 May 10. PubMed PMID: 29360139; PubMed Central PMCID: PMC6033667. 10: Fodor M, Price E, Wang P, Lu H, Argintaru A, Chen Z, Glick M, Hao HX, Kato M, Koenig R, LaRochelle JR, Liu G, McNeill E, Majumdar D, Nishiguchi GA, Perez LB, Paris G, Quinn CM, Ramsey T, Sendzik M, Shultz MD, Williams SL, Stams T, Blacklow SC, Acker MG, LaMarche MJ. Dual Allosteric Inhibition of SHP2 Phosphatase. ACS Chem Biol. 2018 Mar 16;13(3):647-656. doi: 10.1021/acschembio.7b00980. Epub 2018 Jan 18. PubMed PMID: 29304282. 11: Yang H, Jiang H, Song Y, Chen DJ, Shen XJ, Chen JH. Neutrophil CD16b crosslinking induces lipid raft-mediated activation of SHP-2 and affects cytokine expression and retarded neutrophil apoptosis. Exp Cell Res. 2018 Jan 1;362(1):121-131. doi: 10.1016/j.yexcr.2017.11.009. Epub 2017 Nov 11. PubMed PMID: 29137913. 12: Flemming A. Cancer: Allosteric phosphatase inhibitor puts brake on cancer cells. Nat Rev Drug Discov. 2016 Jul 29;15(8):530-1. doi: 10.1038/nrd.2016.157. PubMed PMID: 27469230. 13: Chen YN, LaMarche MJ, Chan HM, Fekkes P, Garcia-Fortanet J, Acker MG, Antonakos B, Chen CH, Chen Z, Cooke VG, Dobson JR, Deng Z, Fei F, Firestone B, Fodor M, Fridrich C, Gao H, Grunenfelder D, Hao HX, Jacob J, Ho S, Hsiao K, Kang ZB, Karki R, Kato M, Larrow J, La Bonte LR, Lenoir F, Liu G, Liu S, Majumdar D, Meyer MJ, Palermo M, Perez L, Pu M, Price E, Quinn C, Shakya S, Shultz MD, Slisz J, Venkatesan K, Wang P, Warmuth M, Williams S, Yang G, Yuan J, Zhang JH, Zhu P, Ramsey T, Keen NJ, Sellers WR, Stams T, Fortin PD. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature. 2016 Jul 7;535(7610):148-52. Epub 2016 Jun 29. PubMed PMID: 27362227. 14: Garcia Fortanet J, Chen CH, Chen YN, Chen Z, Deng Z, Firestone B, Fekkes P, Fodor M, Fortin PD, Fridrich C, Grunenfelder D, Ho S, Kang ZB, Karki R, Kato M, Keen N, LaBonte LR, Larrow J, Lenoir F, Liu G, Liu S, Lombardo F, Majumdar D, Meyer MJ, Palermo M, Perez L, Pu M, Ramsey T, Sellers WR, Shultz MD, Stams T, Towler C, Wang P, Williams SL, Zhang JH, LaMarche MJ. Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor. J Med Chem. 2016 Sep 8;59(17):7773-82. doi: 10.1021/acs.jmedchem.6b00680. Epub 2016 Jul 12. PubMed PMID: 27347692.