SCH772984 | CAS#942183-80-4 | ERK inhibitor

MedKoo Cat#: 406578 | Name: SCH772984

Description:

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

SCH772984 is an potent and selective ERK inhibitor with potential anticancer activity. SCH722984 showed activity against BRAF mutant, NRAS mutant and wild-type melanoma. Combining vemurafenib and SCH722984 in BRAF mutant melanoma was synergistic in a majority of cell lines and significantly delayed the onset of acquired resistance in long term in vitro assays. Therefore, SCH772984 may be clinically applicable as a treatment for non-BRAF mutant melanoma or in BRAF-mutant melanoma with innate or acquired resistance, alone or in combination with BRAF inhibitors.

Chemical Structure

SCH772984

CAS#942183-80-4

Theoretical Analysis

MedKoo Cat#: 406578

Name: SCH772984

CAS#: 942183-80-4

Chemical Formula: C33H33N9O2

Exact Mass: 587.2757

Molecular Weight: 587.67

Elemental Analysis: C, 67.44; H, 5.66; N, 21.45; O, 5.44

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 1,350.00	Ready to ship
500mg	USD 2,950.00	Ready to ship

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Related CAS #

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Synonym

SCH772984; SCH-772984; SCH 772984.

IUPAC/Chemical Name

(R)-1-(2-oxo-2-(4-(4-(pyrimidin-2-yl)phenyl)piperazin-1-yl)ethyl)-N-(3-(pyridin-4-yl)-1H-indazol-5-yl)pyrrolidine-3-carboxamide

InChi Key

HDAJDNHIBCDLQF-RUZDIDTESA-N

InChi Code

InChI=1S/C33H33N9O2/c43-30(42-18-16-41(17-19-42)27-5-2-24(3-6-27)32-35-11-1-12-36-32)22-40-15-10-25(21-40)33(44)37-26-4-7-29-28(20-26)31(39-38-29)23-8-13-34-14-9-23/h1-9,11-14,20,25H,10,15-19,21-22H2,(H,37,44)(H,38,39)/t25-/m1/s1

SMILES Code

O=C([C@H]1CN(CC(N2CCN(C3=CC=C(C4=NC=CC=N4)C=C3)CC2)=O)CC1)NC5=CC6=C(NN=C6C7=CC=NC=C7)C=C5

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 (10mg/mL).

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#CRB50508

View CoA: current batch, Lot#A8T03K01

QC Data

View QC data: current batch, Lot#CRB50508

View QC data: current batch, Lot#A8T03K01

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SCH772984 is an ERK inhibitor with IC50s of 4 and 1 nM for ERK1 and ERK2, respectively.

In vitro activity:

SCH772984 may have potential as a treatment for non-BRAF mutant melanoma or in BRAF-mutant melanoma with innate or acquired resistance. In a panel of 50 melanoma cell lines, 71% of BRAF mutants, 100% of BRAF/NRAS double mutants, 78% of NRAS mutants, and 71% of wild-type melanomas were sensitive to SCH772984. SCH772984 caused G1 arrest and induced apoptosis. Reference: Mol Cancer. 2014 Aug 20;13:194. https://pubmed.ncbi.nlm.nih.gov/25142146/

In vivo activity:

SCH772984 may serve as a potential therapeutic intervention for LPS-induced hypoglycemia. LPS administration resulted in reduced blood glucose levels and gluconeogenesis capacity in mice, but SCH772984 effectively reversed the LPS-induced hypoglycemia. SCH772984 elevated blood glucose levels, increased expression of G6Pase and PEPCK, and inhibited phosphorylated ERK1/2 and phosphorylated Foxo1. Reference: Can J Physiol Pharmacol. 2023 Nov 9. https://pubmed.ncbi.nlm.nih.gov/37944129/

	Solvent	mg/mL	mM
Solubility
	DMSO	7.1	12.08
	DMF	2.0	3.40
	DMF:PBS (pH 7.2) (1:5)	0.1	0.17

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 587.67 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. Wong DJ, Robert L, Atefi MS, Lassen A, Avarappatt G, Cerniglia M, Avramis E, Tsoi J, Foulad D, Graeber TG, Comin-Anduix B, Samatar A, Lo RS, Ribas A. Antitumor activity of the ERK inhibitor SCH772984 [corrected] against BRAF mutant, NRAS mutant and wild-type melanoma. Mol Cancer. 2014 Aug 20;13:194. doi: 10.1186/1476-4598-13-194. Erratum in: Mol Cancer. 2015;14:128. PMID: 25142146; PMCID: PMC4155088. 2. Morris EJ, Jha S, Restaino CR, Dayananth P, Zhu H, Cooper A, Carr D, Deng Y, Jin W, Black S, Long B, Liu J, Dinunzio E, Windsor W, Zhang R, Zhao S, Angagaw MH, Pinheiro EM, Desai J, Xiao L, Shipps G, Hruza A, Wang J, Kelly J, Paliwal S, Gao X, Babu BS, Zhu L, Daublain P, Zhang L, Lutterbach BA, Pelletier MR, Philippar U, Siliphaivanh P, Witter D, Kirschmeier P, Bishop WR, Hicklin D, Gilliland DG, Jayaraman L, Zawel L, Fawell S, Samatar AA. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 2013 Jul;3(7):742-50. doi: 10.1158/2159-8290.CD-13-0070. Epub 2013 Apr 24. PMID: 23614898. 3. Wang Y, Qing S, Yang J, Qian D. SCH772984 ameliorates lipopolysaccharide induced hypoglycemia in mice through reversing MEK/ERK/Foxo1 mediated gluconeogenesis suppression. Can J Physiol Pharmacol. 2023 Nov 9. doi: 10.1139/cjpp-2023-0133. Epub ahead of print. PMID: 37944129. 4. Bian J, Zhu S, Ma W, Li C, Ashraf MA. Analgesic effect and possible mechanism of SCH772984 intrathecal injection on rats with bone cancer pain. Saudi Pharm J. 2016 May;24(3):354-62. doi: 10.1016/j.jsps.2016.04.017. Epub 2016 Apr 26. PMID: 27275127; PMCID: PMC4881153.

In vitro protocol:

In vivo protocol:

1. Wang Y, Qing S, Yang J, Qian D. SCH772984 ameliorates lipopolysaccharide induced hypoglycemia in mice through reversing MEK/ERK/Foxo1 mediated gluconeogenesis suppression. Can J Physiol Pharmacol. 2023 Nov 9. doi: 10.1139/cjpp-2023-0133. Epub ahead of print. PMID: 37944129. 2. Bian J, Zhu S, Ma W, Li C, Ashraf MA. Analgesic effect and possible mechanism of SCH772984 intrathecal injection on rats with bone cancer pain. Saudi Pharm J. 2016 May;24(3):354-62. doi: 10.1016/j.jsps.2016.04.017. Epub 2016 Apr 26. PMID: 27275127; PMCID: PMC4881153.

1: Morris EJ, Jha S, Restaino CR, Dayananth P, Zhu H, Cooper A, Carr D, Deng Y, Jin W, Black S, Long B, Liu J, Dinunzio E, Windsor W, Zhang R, Zhao S, Angagaw MH, Pinheiro EM, Desai J, Xiao L, Shipps G, Hruza A, Wang J, Kelly J, Paliwal S, Gao X, Babu BS, Zhu L, Daublain P, Zhang L, Lutterbach BA, Pelletier MR, Philippar U, Siliphaivanh P, Witter D, Kirschmeier P, Bishop WR, Hicklin D, Gilliland DG, Jayaraman L, Zawel L, Fawell S, Samatar AA. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 2013 Jul;3(7):742-50. doi: 10.1158/2159-8290.CD-13-0070. Epub 2013 Apr 24. PMID: 23614898. 2: Nissan MH, Rosen N, Solit DB. ERK pathway inhibitors: how low should we go? Cancer Discov. 2013 Jul;3(7):719-21. doi: 10.1158/2159-8290.CD-13-0245. PMID: 23847348. 3: Wong DJ, Robert L, Atefi MS, Lassen A, Avarappatt G, Cerniglia M, Avramis E, Tsoi J, Foulad D, Graeber TG, Comin-Anduix B, Samatar A, Lo RS, Ribas A. Antitumor activity of the ERK inhibitor SCH772984 [corrected] against BRAF mutant, NRAS mutant and wild-type melanoma. Mol Cancer. 2014 Aug 20;13:194. doi: 10.1186/1476-4598-13-194. Erratum in: Mol Cancer. 2015 Jul 02;14:128. doi: 10.1186/s12943-015-0393-2. PMID: 25142146; PMCID: PMC4155088. 4: Foda ZH, Seeliger MA. Kinase inhibitors: an allosteric add-on. Nat Chem Biol. 2014 Oct;10(10):796-7. doi: 10.1038/nchembio.1630. Epub 2014 Sep 7. PMID: 25195010. 5: Chaikuad A, Tacconi EM, Zimmer J, Liang Y, Gray NS, Tarsounas M, Knapp S. A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics. Nat Chem Biol. 2014 Oct;10(10):853-60. doi: 10.1038/nchembio.1629. Epub 2014 Sep 7. PMID: 25195011; PMCID: PMC4687050. 6: Rudolph J, Xiao Y, Pardi A, Ahn NG. Slow inhibition and conformation selective properties of extracellular signal-regulated kinase 1 and 2 inhibitors. Biochemistry. 2015 Jan 13;54(1):22-31. doi: 10.1021/bi501101v. Epub 2014 Dec 4. PMID: 25350931; PMCID: PMC4724192. 7: Smit MA, Maddalo G, Greig K, Raaijmakers LM, Possik PA, van Breukelen B, Cappadona S, Heck AJ, Altelaar AF, Peeper DS. ROCK1 is a potential combinatorial drug target for BRAF mutant melanoma. Mol Syst Biol. 2014 Dec 23;10(12):772. doi: 10.15252/msb.20145450. PMID: 25538140; PMCID: PMC4300494. 8: Vogel CJ, Smit MA, Maddalo G, Possik PA, Sparidans RW, van der Burg SH, Verdegaal EM, Heck AJ, Samatar AA, Beijnen JH, Altelaar AF, Peeper DS. Cooperative induction of apoptosis in NRAS mutant melanoma by inhibition of MEK and ROCK. Pigment Cell Melanoma Res. 2015 May;28(3):307-17. doi: 10.1111/pcmr.12364. Epub 2015 Apr 6. PMID: 25728708. 9: Jha S, Morris EJ, Hruza A, Mansueto MS, Schroeder GK, Arbanas J, McMasters D, Restaino CR, Dayananth P, Black S, Elsen NL, Mannarino A, Cooper A, Fawell S, Zawel L, Jayaraman L, Samatar AA. Dissecting Therapeutic Resistance to ERK Inhibition. Mol Cancer Ther. 2016 Apr;15(4):548-59. doi: 10.1158/1535-7163.MCT-15-0172. Epub 2016 Feb 1. PMID: 26832798. 10: Zhou B, Ritt DA, Morrison DK, Der CJ, Cox AD. Protein Kinase CK2α Maintains Extracellular Signal-regulated Kinase (ERK) Activity in a CK2α Kinase- independent Manner to Promote Resistance to Inhibitors of RAF and MEK but Not ERK in BRAF Mutant Melanoma. J Biol Chem. 2016 Aug 19;291(34):17804-15. doi: 10.1074/jbc.M115.712885. Epub 2016 May 17. PMID: 27226552; PMCID: PMC5016172. 11: Bian J, Zhu S, Ma W, Li C, Ashraf MA. Analgesic effect and possible mechanism of SCH772984 intrathecal injection on rats with bone cancer pain. Saudi Pharm J. 2016 May;24(3):354-62. doi: 10.1016/j.jsps.2016.04.017. Epub 2016 Apr 26. PMID: 27275127; PMCID: PMC4881153. 12: Lim J, Kelley EH, Methot JL, Zhou H, Petrocchi A, Chen H, Hill SE, Hinton MC, Hruza A, Jung JO, Maclean JK, Mansueto M, Naumov GN, Philippar U, Raut S, Spacciapoli P, Sun D, Siliphaivanh P. Discovery of 1-(1H-Pyrazolo[4,3-c]pyridin-6-yl)urea Inhibitors of Extracellular Signal- Regulated Kinase (ERK) for the Treatment of Cancers. J Med Chem. 2016 Jul 14;59(13):6501-11. doi: 10.1021/acs.jmedchem.6b00708. Epub 2016 Jul 1. PMID: 27329786. 13: Ryan MB, Finn AJ, Pedone KH, Thomas NE, Der CJ, Cox AD. ERK/MAPK Signaling Drives Overexpression of the Rac-GEF, PREX1, in BRAF- and NRAS-Mutant Melanoma. Mol Cancer Res. 2016 Oct;14(10):1009-1018. doi: 10.1158/1541-7786.MCR-16-0184. Epub 2016 Jul 14. PMID: 27418645; PMCID: PMC5065759. 14: Kim JY, Welsh EA, Fang B, Bai Y, Kinose F, Eschrich SA, Koomen JM, Haura EB. Phosphoproteomics Reveals MAPK Inhibitors Enhance MET- and EGFR-Driven AKT Signaling in KRAS-Mutant Lung Cancer. Mol Cancer Res. 2016 Oct;14(10):1019-1029. doi: 10.1158/1541-7786.MCR-15-0506. Epub 2016 Jul 15. PMID: 27422710; PMCID: PMC5065770. 15: Kawasaki Y, Sakimura A, Park CM, Tomaru R, Tanaka T, Ozawa T, Zhou Y, Narita K, Kishi H, Muraguchi A, Sakurai H. Feedback control of ErbB2 via ERK-mediated phosphorylation of a conserved threonine in the juxtamembrane domain. Sci Rep. 2016 Aug 17;6:31502. doi: 10.1038/srep31502. PMID: 27531070; PMCID: PMC4987620. 16: Krepler C, Xiao M, Samanta M, Vultur A, Chen HY, Brafford P, Reyes-Uribe PI, Halloran M, Chen T, He X, Hristova D, Liu Q, Samatar AA, Davies MA, Nathanson KL, Fukunaga-Kalabis M, Herlyn M, Villanueva J. Targeting Notch enhances the efficacy of ERK inhibitors in BRAF-V600E melanoma. Oncotarget. 2016 Nov 1;7(44):71211-71222. doi: 10.18632/oncotarget.12078. PMID: 27655717; PMCID: PMC5342073. 17: Liu Y, Li F, Gao F, Xing L, Qin P, Liang X, Zhang J, Qiao X, Lin L, Zhao Q, Du L. Periostin promotes tumor angiogenesis in pancreatic cancer via Erk/VEGF signaling. Oncotarget. 2016 Jun 28;7(26):40148-40159. doi: 10.18632/oncotarget.9512. PMID: 27223086; PMCID: PMC5129999. 18: Sun WJ, Huang H, He B, Hu DH, Li PH, Yu YJ, Zhou XH, Lv Z, Zhou L, Hu TY, Yao ZC, Lu MD, Shen X, Zheng ZQ. Romidepsin induces G2/M phase arrest via Erk/cdc25C/cdc2/cyclinB pathway and apoptosis induction through JNK/c-Jun/caspase3 pathway in hepatocellular carcinoma cells. Biochem Pharmacol. 2017 Mar 1;127:90-100. doi: 10.1016/j.bcp.2016.12.008. Epub 2016 Dec 22. PMID: 28012958. 19: Negishi T, Matsumoto M, Kobayashi Y, Kojima M, Sakaguchi F, Takahata K, Kanehira T, Arakaki R, Aoyama Y, Yoshida H, Yamada R, Sumiyoshi N, Tashiro T, Hirano S, Yoshida K, Yukawa K. Dysregulation of MAP Kinase Signaling Pathways Including p38MAPK, SAPK/JNK, and ERK1/2 in Cultured Rat Cerebellar Astrocytes Exposed to Diphenylarsinic Acid. Toxicol Sci. 2017 Apr 1;156(2):509-519. doi: 10.1093/toxsci/kfx012. PMID: 28087833. 20: Trousil S, Chen S, Mu C, Shaw FM, Yao Z, Ran Y, Shakuntala T, Merghoub T, Manstein D, Rosen N, Cantley LC, Zippin JH, Zheng B. Phenformin Enhances the Efficacy of ERK Inhibition in NF1-Mutant Melanoma. J Invest Dermatol. 2017 May;137(5):1135-1143. doi: 10.1016/j.jid.2017.01.013. Epub 2017 Jan 28. PMID: 28143781; PMCID: PMC5392423.