LY3214996 - Moligand™, 10mM in DMSO , Mitogen-activated protein kinase; ERK1/ERK2 inhibitor, CAS No.1951483-29-6, Mitogen-activated protein kinase; ERK1/ERK2 inhibitor

CAS: 1951483-29-6 Cat. No.: L408245 Molecular Weight: 453.56

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

4H-​Thieno[2,​3-​c]​pyrrol-​4-​one, 5,​6-​dihydro-​6,​6-​dimethyl-​2-​[2-​[(1-​methyl-​1H-​pyrazol-​5-​yl)​amino]​-​4-​pyrimidinyl]​-​5-​[2-​(4-​morpholinyl)​ethyl]​-

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

LY3214996 LY3214996 is a selective and novel ERK1/2 inhibitor with IC50 of 5 nM for both enzymes in biochemical assays. It potently inhibits cellular phospho-RSK1 in BRAF and RAS mutant cancer cell lines.
In vitro

In an unbiased tumor cell panel sensitivity profiling for inhibition of cell proliferation, tumor cells with MAPK pathway alterations including BRAF, NRAS or KRAS mutation are generally sensitivity to LY3214996. LY3214996 possesses an optimal balance of potency (hERK1 IC50 5 nM, hERK2 IC50 5nM, pRSK IC50 0.43 µM) and solubility.

In vivo

In tumor xenograft models, LY3214996 inhibits PD biomarker phospho-p90RSK1 in tumors and the PD effects are correlated with compound exposures and anti-tumor activities. LY3214996 shows either similar or superior anti-tumor activity as compared to other published ERK inhibitors in BRAF or RAS mutant cell lines and xenograft models. Oral administration of single-agent LY3214996 significantly inhibits tumor growth in vivo and is well tolerated in BRAF or NRAS mutant melanoma, BRAF or KRAS mutant colorectal, lung and pancreatic cancer xenografts or PDX models. In addition, LY3214996 has anti-tumor activity in a vemurafenib-resistant A375 melanoma xenograft model due to MAPK reactivation, may have potential for treatment of melanoma patients who have failed BRAF therapies. More importantly, LY3214996 can be combined with investigational and approved agents in preclinical models, particularly KRAS mutant models. Combination treatment of LY3214996 and CDK4/6 inhibitor abemaciclib is well tolerated and results in potent tumor growth inhibition or regression in multiple in vivo cancer models, including KRAS mutant colorectal and non-small cell lung cancers. LY3214996 has good PK properties (dog, AUCoral 23800 nM*hr, CL 12.1 mL/min/kg, bioavailability 75.4%), IVTI (TED50 =16 mg/kg pRSK1) and demonstrates significant in vivo efficacy in several human cancer xenograft models.
Cell Data

cell lines：

Concentrations：

Incubation Time：

Powder Purity:≥99%

Specifications

Synonyms

4H-​Thieno[2, ​3-​c]​pyrrol-​4-​one, 5, ​6-​dihydro-​6, ​6-​dimethyl-​2-​[2-​[(1-​methyl-​1H-​pyrazol-​5-​yl)​amino]​-​4-​pyrimidinyl]​-​5-​[2-​(4-​morpholinyl)​ethyl]​-

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

LY3214996 is a selective and novel ERK1/2 inhibitor with IC50 of 5 nM for both enzymes in biochemical assays. It potently inhibits cellular phospho-RSK1 in BRAF and RAS mutant cancer cell lines.

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Mitogen-activated protein kinase; ERK1/ERK2 inhibitor

Product Properties

• ALogP: 2.664
• hba_count: 5
• HBD Count: 1
• Rotatable Bond: 6

Names and Identifiers

• Isomeric SMILES: CC1(C2=C(C=C(S2)C3=NC(=NC=C3)NC4=CC=NN4C)C(=O)N1CCN5CCOCC5)C
• Molecular Weight: 453.56
• Reaxy-Rn: 29638130
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=29638130&ln=

Chemical and Physical Properties

• DMSO(mg / mL) Max Solubility: 27
• DMSO(mM) Max Solubility: 59.529059
• Water(mg / mL) Max Solubility: ＜1

References

1. Chen Xue, Zhou Xing-Yue, Lan Cai, Fu Hai-Jun, Li Zhi-Chao, Chen Meng-Yi, Wen Yong-Ping, Yu Lu, Qin Da-Lian, Wu An-Guo, Wu Jian-Ming, Zhou Xiao-Gang.  (2025)  Araloside A Induces Raf/MEK/ERK-Dependent Autophagy to Mitigate Alzheimer’s and Parkinson’s Pathology in Cellular and C. elegans Models.  MOLECULAR NEUROBIOLOGY,      [PMID:40742404] [10.1007/s12035-025-05242-4]