WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406578
CAS#: 942183-80-4
Description: 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.
Hodoodo Cat#: H406578
Name: SCH772984
CAS#: 942183-80-4
Chemical Formula: C33H33N9O2
Exact Mass: 587.28
Molecular Weight: 587.674
Elemental Analysis: C, 67.44; H, 5.66; N, 21.45; O, 5.44
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:
| 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 | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 7.1 | 12.08 | |
| DMF | 2.0 | 3.40 | |
| DMF:PBS (pH 7.2) (1:5) | 0.1 | 0.17 |
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: | 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. |
| 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: Chaikuad A, M C Tacconi E, 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. PubMed PMID: 25195011.
2: 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 SCH722984 against BRAF mutant, NRAS mutant and wild-type melanoma. Mol Cancer. 2014 Aug 20;13:194. doi: 10.1186/1476-4598-13-194. PubMed PMID: 25142146; PubMed Central PMCID: PMC4155088.
3: 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. PubMed PMID: 23847348.
4: 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. PubMed PMID: 23614898.
