| Identification | More | [Name]
SCH772984 | [CAS]
942183-80-4 | [Synonyms]
SCH772984
SCH772984/SCH-772984
(R)-1-(2-oxo-2-(4-(4-(pyrimidin-2-yl)phenyl)piperazin-1-yl)ethyl)-N-(3-(pyridin-4-yl)-1H-indazol-5-
(3R)-1-[2-Oxo-2-[4-[4-(2-pyrimidinyl)phenyl]-1-piperazinyl]ethyl]-N-[3-(4-pyridinyl)-1H-indazol-5-yl]-3-pyrrolidinecarboxamide
(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
(3R)-1-[2-Oxo-2-[4-[4-(2-pyrimidinyl)phenyl]-1-piperazinyl]ethyl]-N-[3-(4-pyridinyl)-1H-indazol-5-yl]-3-pyrrolidinecarboxamide SCH772984 | [EINECS(EC#)]
1592732-453-0 | [Molecular Formula]
C33H33N9O2 | [MDL Number]
MFCD11878503 | [MOL File]
942183-80-4.mol | [Molecular Weight]
587.685 |
| Chemical Properties | Back Directory | [Melting point ]
>214°C (dec.) | [Boiling point ]
857.3±65.0 °C(Predicted) | [density ]
1.353±0.06(20.0000℃) | [storage temp. ]
Refrigerator | [solubility ]
DMSO (Slightly) | [form ]
Solid | [pka]
12.05±0.40(Predicted) | [color ]
Pale Yellow | [InChIKey]
HDAJDNHIBCDLQF-RUZDIDTESA-N | [SMILES]
N1(CC(=O)N2CCN(C3=CC=C(C4=NC=CC=N4)C=C3)CC2)CC[C@@H](C(NC2C=CC3=C(C=2)C(C2C=CN=CC=2)=NN3)=O)C1 | [CAS DataBase Reference]
942183-80-4 |
| Hazard Information | Back Directory | [Description]
The extracellular regulated kinases 1 and 2 (ERK1/2) are functionally redundant kinases activated by a variety of growth factors and mitogens.1 SCH 772984 is a potent inhibitor of ERK1 and ERK2 (IC50s = 4 and 1 nM, respectively).2 It is highly selective, with only seven kinases of 300 tested showing more than 50% inhibition at a concentration of 1 μM. SCH 772984 has nanomolar cytotoxicity in tumor cells with mutations in BRAF, NRAS, or KRAS.2 It is effective in vivo, inducing regression of xenograft tumors in mice. SCH 772984 displays slow binding kinetics, binding to a novel binding pocket in inactive ERK isoforms.3 | [Uses]
SCH772984 is a novel and selective inhibitor of ERK1/2 that displays behaviors of both type I and type II kinase inhibitors and has nanomolar cellular potency in tumor cells with mutations in BRAF, NRA5, or KRAS and induces tumor regressions in xenograft models. | [Definition]
ChEBI: SCH772984 is a member of the class of indazoles that is 1H-indazole substituted by pyridin-4-yl and {[(3R)-1-(2-oxo-2-{4-[4-(pyrimidin-2-yl)phenyl]piperazin-1-yl}ethyl)pyrrolidin-3-yl]carbonyl}amino groups at positions 3 and 5, respectively. It is a potent inhibitor of mitogen-activated protein kinases ERK1 and ERK2 (IC50 = 4 and 1 nM, respectively) that exhibits anti-cancer properties. It has a role as an antineoplastic agent, an EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor, an apoptosis inducer and an analgesic. It is a member of pyridines, a biaryl, a secondary carboxamide, a pyrrolidinecarboxamide, a member of indazoles, a tertiary amino compound, a N-acylpiperazine, a N-arylpiperazine, a member of pyrimidines, a N-alkylpyrrolidine and a tertiary carboxamide. | [in vivo]
SCH772984 (12.5-50 mg/kg; i.p.; twice daily for 14 days) leads to 98% tumor regression[1].
Dose-dependent antitumor activity is also observed in the KRAS-mutant pancreatic MiaPaCa model, with 36% regression at 50 mg/kg twice daily. Importantly, tumor regression is accompanied by robust inhibition of ERK phosphorylation in tumor tissue. SCH772984 is well tolerated on this schedule as measured by morbidity, lethality, or body weight loss[1]. | Animal Model: | Female nude mice bearing human LOX BRAFV600E tumors[1] | | Dosage: | 12.5, 25, 50 mg/kg | | Administration: | Intraperitoneal injection; twice daily for 14 days | | Result: | Tumor regressions were observed at all doses, such as 17% at 12.5 mg/kg, 84% at 25 mg/kg, and 98% at 50 mg/kg). |
| [target]
ERK1 | [IC 50]
ERK2: 1 nM (IC50); ERK1: 4 nM (IC50) | [storage]
Store at -20°C | [References]
[1] ERICK J MORRIS. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors.[J]. Cancer discovery, 2013, 3 7: 742-750. DOI: 10.1158/2159-8290.cd-13-0070
[2] APIRAT CHAIKUAD. A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics[J]. Nature chemical biology, 2014, 10 10: 853-860. DOI: 10.1038/nchembio.1629 |
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| Company Name: |
Moltt Biocem Co., Ltd.
|
| Telephone: |
+86-21-38682181 15900741819 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList15856/0_EN.htm |
| Company Name: |
LETOPHARM LIMITED
|
| Telephone: |
+86-21-5821 5861 |
| Website: |
www.letopharm.com |
|