SCH772984 HCl
SCH772984 HCl is a specific inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2), with IC50 values of 4 nM and 1 nM, respectively [1].
ERK1/2 is a mitogen-activated protein kinase (MAPK) which is involved in the development of various cancers, especially the ones with BRAF or RAS mutations. Phospho-ERK reactivation in cancer cells is associated with resistance to BRAF and MEK inhibitors [1].
In BRAFV600E-mutant human melanoma cell line LOXIMV1 (LOX), SCH772984 at 0 ~ 300 nM inhibited phosphorylation of the ERK substrate p90 ribosomal S6 kinase in a dose-dependent manner. SCH772984 also reduced phosphorylation of residues in the activation loop of ERK itself. In addition, for approximately 88% and 49% of BRAF-mutant or RAS-mutant tumor lines, SCH772984 exhibited antiproliferative activity with EC50 values < 500 nM. SCH772984 effectively inhibited MAPK signaling and cell proliferation even in tumor cells resistant to concurrent treatment with BRAF and MAP-ERK kinase (MEK) inhibitors [1].
In female nude mice bearing human LOX BRAFV600E tumors, SCH772984 (12.5, 25, 50 mg/kg, i.p., b.i.d., for 14 days) induced tumor regressions in a dose-dependent manner, and 98% tumor regression was achieved at the largest dose [1].
Reference:
[1]. Morris E J, Jha S, Restaino C R, et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discovery, 2013, 3(7): 742-750.
- 1. Josh L. Stern, Lindsay F. Rizzardi, et al."Apurinic/apyrimidinic endodeoxyribonuclease 2 (APEX2/APE2) is required for efficient expression of TERT in human embryonic stem cells." September 23, 2024.
- 2. Spandana Kotian, Lindsay F. Rizzardi, et al. "MEK1/2 kinases cooperate with c-Myc:MAX to prevent polycomb repression of TERT in human pluripotent stem cells." September 18, 2024.
- 3. Lydia Daboussi, Giancarlo Costaguta, et al. "Mitf is a Schwann cell sensor of axonal integrity that drives nerve repair." Cell Rep. 2023 Nov 28;42(11):113282 PMID: 38007688
- 4. Sridhar Tatarao Narla, Joanne Lindsey Duara, et al. "Role of ERK signaling in bladder urothelium in response to cyclophosphamide injury." Physiol Rep. 2022 Jul;10(14):10.14814/phy2.15378. PMID: 35854647
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 624.17 |
| Cas No. | 942183-80-4 (free base) |
| Formula | C33H34ClN9O2 |
| Solubility | ≥23.5 mg/mL in H2O with gentle warming; insoluble in EtOH; ≥16.27 mg/mL in DMSO |
| SDF | Download SDF |
| Canonical SMILES | O=C(N1CCN(C2=CC=C(C3=NC=CC=N3)C=C2)CC1)CN4CC[C@@](/C(O)=N/C5=CC(C(C6=CC=NC=C6)=NN7)=C7C=C5)([H])C4.Cl |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
BRAFV600E-mutant human melanoma cell line LOXIMV1 (LOX) |
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Reaction Conditions |
0 ~ 300 nM SCH772984 for 24 h incubation |
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Applications |
SCH772984 inhibited phosphorylation of the ERK substrate p90 ribosomal S6 kinase in a dose-dependent manner. SCH772984 also reduced phosphorylation of residues in the activation loop of ERK itself, a modification catalyzed by the ERK-activating kinases, MEK 1 and MEK 2. |
| Animal experiment:[1] | |
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Animal models |
Female nude mice bearing human LOX BRAFV600E tumors |
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Dosage form |
12.5, 25, 50 mg/kg Twice daily (b.i.d.) by intraperitoneal route (i.p.) for 14 days |
|
Applications |
In female nude mice bearing human LOX BRAFV600E tumors, SCH772984 (12.5, 25, 50 mg/kg, i.p., b.i.d., for 14 days) induced tumor regressions in a dose-dependent manner, and 98% tumor regression was achieved at the largest dose. |
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Note |
The technical data provided above is for reference only. |
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References: 1. Morris E J, Jha S, Restaino C R, et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discovery, 2013, 3(7): 742-750. |
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Quality Control & MSDS
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Chemical structure
