RMC-4550 | CAA#2172651-73-7 | SHP2

MedKoo Cat#: 407910 | Name: RMC-4550

Description:

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

RMC-4550 is a potent and selective SHP2 inhibitor. RMC-4550 identified as a high quality tool compound to study the role of SHP2 in tumor biology, both in vitro and in vivo in rodents. SHP2 is a convergent signalling node and inhibition of SHP2 is effective in targeting both upstream (RTK-driven) and downstream (RAS-GTP dependent) mutations in the RAS-MAPK pathway

Chemical Structure

RMC-4550

CAS#2172651-73-7

Theoretical Analysis

MedKoo Cat#: 407910

Name: RMC-4550

CAS#: 2172651-73-7

Chemical Formula: C21H26Cl2N4O2

Exact Mass: 436.1433

Molecular Weight: 437.37

Elemental Analysis: C, 57.67; H, 5.99; Cl, 16.21; N, 12.81; O, 7.32

Price and Availability

Size	Price	Availability
1mg	USD 75.00	Ready to ship
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 550.00	Ready to ship
50mg	USD 950.00	Ready to ship
100mg	USD 1,650.00	Ready to ship
200mg	USD 2,750.00	Ready to ship

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Related CAS #

No Data

Synonym

RMC-4550; RMC4550; RMC 4550.

IUPAC/Chemical Name

(3-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-6-(2,3-dichlorophenyl)-5-methylpyrazin-2-yl)methanol

InChi Key

IKUYEYLZXGGCRD-ORAYPTAESA-N

InChi Code

InChI=1S/C21H26Cl2N4O2/c1-12-18(14-4-3-5-15(22)17(14)23)26-16(10-28)20(25-12)27-8-6-21(7-9-27)11-29-13(2)19(21)24/h3-5,13,19,28H,6-11,24H2,1-2H3/t13-,19+/m0/s1

SMILES Code

ClC1=C(Cl)C(C2=NC(CO)=C(N3CCC4(CO[C@@H](C)[C@H]4N)CC3)N=C2C)=CC=C1

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#T21D09P19

View CoA: current batch, Lot#T20D07P21

QC Data

View QC data: current batch, Lot#T20D07P21

View QC data: current batch, Lot#T21D09P19

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

RMC-4550 is an inhibitor of Src homology region 2 domain-containing phosphatase 2 (SHP-2; IC50 = 1.55 nM). It inhibits tumor ERK phosphorylation in a KYSE-520 human esophageal cancer xenograft model in a dose-dependent manner.

In vitro activity:

Use SHP099 and RMC-4550 resulted in inhibition of cell growth in anaplastic lymphoma kinase (ALK)-driven neuroblastoma (NB) cells. There was a strong synergistic effect of combined ALK and SHP2 inhibition that was specific to ALK-driven NB cells, suggesting a potential therapeutic option for ALK-driven NB. Reference: J Mol Biol. 2021 Sep 17;433(19):167158. https://pubmed.ncbi.nlm.nih.gov/34273398/

In vivo activity:

Administration of RMC-4550 led to decidualization deficiency and embryo absorption in mice. Reduced expression of SHP2 was detected in the decidua of recurrent miscarriage patients. Results revealed that SHP2 is key to the progesterone receptor’s nuclear localization, meaning that reduced expression of SHP2 might be engaged in the pathogenesis of recurrent miscarriages. Reference: Reproduction. 2023 Jun 9;166(1):37-53. https://pubmed.ncbi.nlm.nih.gov/37184079/

	Solvent	mg/mL	mM
Solubility
	DMSO	21.9	50.10

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 437.37 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. Uçkun E, Siaw JT, Guan J, Anthonydhason V, Fuchs J, Wolfstetter G, Hallberg B, Palmer RH. BioID-Screening Identifies PEAK1 and SHP2 as Components of the ALK Proximitome in Neuroblastoma Cells. J Mol Biol. 2021 Sep 17;433(19):167158. doi: 10.1016/j.jmb.2021.167158. Epub 2021 Jul 15. PMID: 34273398. 2. Quintana E, Schulze CJ, Myers DR, Choy TJ, Mordec K, Wildes D, Shifrin NT, Belwafa A, Koltun ES, Gill AL, Singh M, Kelsey S, Goldsmith MA, Nichols R, Smith JAM. Allosteric Inhibition of SHP2 Stimulates Antitumor Immunity by Transforming the Immunosuppressive Environment. Cancer Res. 2020 Jul 1;80(13):2889-2902. doi: 10.1158/0008-5472.CAN-19-3038. Epub 2020 Apr 29. PMID: 32350067. 3. Chen L, Zhao W, Li M, Yang Y, Tian C, Zhang D, Chang Z, Zhang Y, Zhao ZJ, Chen Y, Ma L. SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor. Reproduction. 2023 Jun 9;166(1):37-53. doi: 10.1530/REP-22-0367. PMID: 37184079; PMCID: PMC10304905. 4. Panchal N, Houghton BC, Vassalou E, Thrasher AJ, Booth C. Allosteric inhibition of SHP2 rescues functional T-cell abnormalities in SAP deficiency. J Allergy Clin Immunol. 2022 Dec;150(6):1507-1516.e7. doi: 10.1016/j.jaci.2022.06.021. Epub 2022 Jul 14. PMID: 35839843.

In vitro protocol:

In vivo protocol:

1. Chen L, Zhao W, Li M, Yang Y, Tian C, Zhang D, Chang Z, Zhang Y, Zhao ZJ, Chen Y, Ma L. SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor. Reproduction. 2023 Jun 9;166(1):37-53. doi: 10.1530/REP-22-0367. PMID: 37184079; PMCID: PMC10304905. 2. Panchal N, Houghton BC, Vassalou E, Thrasher AJ, Booth C. Allosteric inhibition of SHP2 rescues functional T-cell abnormalities in SAP deficiency. J Allergy Clin Immunol. 2022 Dec;150(6):1507-1516.e7. doi: 10.1016/j.jaci.2022.06.021. Epub 2022 Jul 14. PMID: 35839843.

1: Frank KJ, Mulero-Sánchez A, Berninger A, Ruiz-Cañas L, Bosma A, Görgülü K, Wu N, Diakopoulos KN, Kaya-Aksoy E, Ruess DA, Kabacaoğlu D, Schmidt F, Kohlmann L, van Tellingen O, Thijssen B, van de Ven M, Proost N, Kossatz S, Weber WA, Sainz B Jr, Bernards R, Algül H, Lesina M, Mainardi S. Extensive preclinical validation of combined RMC-4550 and LY3214996 supports clinical investigation for KRAS mutant pancreatic cancer. Cell Rep Med. 2022 Nov 15;3(11):100815. doi: 10.1016/j.xcrm.2022.100815. PMID: 36384095; PMCID: PMC9729824. 2: Wang RR, Liu WS, Zhou L, Ma Y, Wang RL. Probing the acting mode and advantages of RMC-4550 as an Src-homology 2 domain-containing protein tyrosine phosphatase (SHP2) inhibitor at molecular level through molecular docking and molecular dynamics. J Biomol Struct Dyn. 2020 Mar;38(5):1525-1538. doi: 10.1080/07391102.2019.1613266. Epub 2019 May 13. PMID: 31043123. 3: Popescu B, Stahlhut C, Tarver TC, Wishner S, Lee BJ, Peretz CAC, Luck C, Phojanakong P, Camara Serrano JA, Hongo H, Rivera JM, Xirenayi S, Chukinas JA, Steri V, Tasian SK, Stieglitz E, Smith CC. Allosteric SHP2 inhibition increases apoptotic dependency on BCL2 and synergizes with venetoclax in FLT3- and KIT- mutant AML. Cell Rep Med. 2023 Nov 21;4(11):101290. doi: 10.1016/j.xcrm.2023.101290. PMID: 37992684; PMCID: PMC10694768. 4: Lee C, Rhee I. Important roles of protein tyrosine phosphatase PTPN12 in tumor progression. Pharmacol Res. 2019 Jun;144:73-78. doi: 10.1016/j.phrs.2019.04.011. Epub 2019 Apr 5. PMID: 30959160. 5: Vemulapalli V, Donovan KA, Seegar TCM, Rogers JM, Bae M, Lumpkin RJ, Cao R, Henke MT, Ray SS, Fischer ES, Cuny GD, Blacklow SC. Targeted Degradation of the Oncogenic Phosphatase SHP2. Biochemistry. 2021 Aug 31;60(34):2593-2609. doi: 10.1021/acs.biochem.1c00377. Epub 2021 Aug 19. PMID: 34411482; PMCID: PMC8410664. 6: Larson KC, Martens LH, Marconi M, Dejesus C, Bruhn S, Miller TA, Tate B, Levenson JM. Preclinical translational platform of neuroinflammatory disease biology relevant to neurodegenerative disease. J Neuroinflammation. 2024 Jan 31;21(1):37. doi: 10.1186/s12974-024-03029-3. PMID: 38297405; PMCID: PMC10832185. 7: Pandey G, Mazzacurati L, Rowsell TM, Horvat NP, Amin NE, Zhang G, Akuffo AA, Colin-Leitzinger CM, Haura EB, Kuykendall AT, Zhang L, Epling-Burnette PK, Reuther GW. SHP2 inhibition displays efficacy as a monotherapy and in combination with JAK2 inhibition in preclinical models of myeloproliferative neoplasms. Am J Hematol. 2024 Jun;99(6):1040-1055. doi: 10.1002/ajh.27282. Epub 2024 Mar 5. PMID: 38440831; PMCID: PMC11096011. 8: Panchal N, Houghton BC, Vassalou E, Thrasher AJ, Booth C. Allosteric inhibition of SHP2 rescues functional T-cell abnormalities in SAP deficiency. J Allergy Clin Immunol. 2022 Dec;150(6):1507-1516.e7. doi: 10.1016/j.jaci.2022.06.021. Epub 2022 Jul 14. PMID: 35839843. 9: Zhou P, Xiao M, Li W, Sun X, Bai Y, Meng F, Zhu Z, Yuan W, Sun K. SHP2 Inhibitors Show Anti-Myeloma Activity and Synergize With Bortezomib in the Treatment of Multiple Myeloma. Front Pharmacol. 2022 Apr 6;13:841308. doi: 10.3389/fphar.2022.841308. PMID: 35462913; PMCID: PMC9019471. 10: Sealover NE, Theard PL, Hughes JM, Linke AJ, Daley BR, Kortum RL. In situ modeling of acquired resistance to RTK/RAS pathway targeted therapies. bioRxiv [Preprint]. 2023 Jun 28:2023.01.27.525958. doi: 10.1101/2023.01.27.525958. Update in: iScience. 2023 Dec 11;27(1):108711. doi: 10.1016/j.isci.2023.108711. PMID: 36747633; PMCID: PMC9901014. 11: Quintana E, Schulze CJ, Myers DR, Choy TJ, Mordec K, Wildes D, Shifrin NT, Belwafa A, Koltun ES, Gill AL, Singh M, Kelsey S, Goldsmith MA, Nichols R, Smith JAM. Allosteric Inhibition of SHP2 Stimulates Antitumor Immunity by Transforming the Immunosuppressive Environment. Cancer Res. 2020 Jul 1;80(13):2889-2902. doi: 10.1158/0008-5472.CAN-19-3038. Epub 2020 Apr 29. PMID: 32350067. 12: Uçkun E, Siaw JT, Guan J, Anthonydhason V, Fuchs J, Wolfstetter G, Hallberg B, Palmer RH. BioID-Screening Identifies PEAK1 and SHP2 as Components of the ALK Proximitome in Neuroblastoma Cells. J Mol Biol. 2021 Sep 17;433(19):167158. doi: 10.1016/j.jmb.2021.167158. Epub 2021 Jul 15. PMID: 34273398. 13: Chen L, Zhao W, Li M, Yang Y, Tian C, Zhang D, Chang Z, Zhang Y, Zhao ZJ, Chen Y, Ma L. SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor. Reproduction. 2023 Jun 9;166(1):37-53. doi: 10.1530/REP-22-0367. PMID: 37184079; PMCID: PMC10304905. 14: Sisler DJ, Hinz TK, Le AT, Kleczko EK, Nemenoff RA, Heasley LE. Evaluation of KRASG12C inhibitor responses in novel murine KRASG12C lung cancer cell line models. Front Oncol. 2023 Feb 8;13:1094123. doi: 10.3389/fonc.2023.1094123. PMID: 36845684; PMCID: PMC9945252. 15: Ito M, Codony-Servat J, Giménez-Capitán A, Serra-Mitjans M, Pérez-Ochoa F, Llige D, Chaib I, Rami-Porta R, Obiols C, Call S, Iglesias M, Belda-Sanchis J, Tarroch-Sarasa X, Karachaliou N, Molina-Vila MA, Okada M, Rosell R. Src-Homology 2 Domain-Containing Phosphatase 2 in Resected EGFR Mutation-Positive Lung Adenocarcinoma. JTO Clin Res Rep. 2020 Aug 21;1(4):100084. doi: 10.1016/j.jtocrr.2020.100084. PMID: 34589963; PMCID: PMC8474259. 16: Nichols RJ, Haderk F, Stahlhut C, Schulze CJ, Hemmati G, Wildes D, Tzitzilonis C, Mordec K, Marquez A, Romero J, Hsieh T, Zaman A, Olivas V, McCoach C, Blakely CM, Wang Z, Kiss G, Koltun ES, Gill AL, Singh M, Goldsmith MA, Smith JAM, Bivona TG. RAS nucleotide cycling underlies the SHP2 phosphatase dependence of mutant BRAF-, NF1- and RAS-driven cancers. Nat Cell Biol. 2018 Sep;20(9):1064-1073. doi: 10.1038/s41556-018-0169-1. Epub 2018 Aug 13. PMID: 30104724; PMCID: PMC6115280. 17: Chen X, Zou F, Hu Z, Du G, Yu P, Wang W, Wang H, Ye L, Tian J. PCC0208023, a potent SHP2 allosteric inhibitor, imparts an antitumor effect against KRAS mutant colorectal cancer. Toxicol Appl Pharmacol. 2020 Jul 1;398:115019. doi: 10.1016/j.taap.2020.115019. Epub 2020 Apr 24. PMID: 32335126. 18: Valencia-Sama I, Ladumor Y, Kee L, Adderley T, Christopher G, Robinson CM, Kano Y, Ohh M, Irwin MS. NRAS Status Determines Sensitivity to SHP2 Inhibitor Combination Therapies Targeting the RAS-MAPK Pathway in Neuroblastoma. Cancer Res. 2020 Aug 15;80(16):3413-3423. doi: 10.1158/0008-5472.CAN-19-3822. Epub 2020 Jun 25. PMID: 32586982.