Home MAPK ERK inhibitor Temuterkib (LY3214996) For research use only.

Temuterkib (LY3214996)

Temuterkib (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.

Temuterkib (LY3214996) Chemical Structure

Temuterkib (LY3214996) Chemical Structure

CAS No. 1951483-29-6

Purity & Quality Control

Temuterkib (LY3214996) Related Products

Signaling Pathway

ERK Signaling Pathways

ERK Signaling Pathway

Biological Activity

Description Temuterkib (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.
Targets
ERK1 [1]
(Cell-free assay)		 ERK2 [1]
(Cell-free assay)
5 nM 5 nM
In vitro
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[1].

LY3214996 possesses an optimal balance of potency (hERK1 IC50 5 nM, hERK2 IC50 5nM, pRSK IC50 0.43 µM) and solubility[2].
In Vivo
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 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 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[1].

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[2].
Animal Research Animal Models NSG mice
Dosages 100 mg/kg
Administration o.g.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04916236 Recruiting
Pancreatic Cancer|Colorectal Cancer|Non-small Cell Lung Cancer|KRAS Mutation-Related Tumors
The Netherlands Cancer Institute|Lustgarten Foundation
 March 31 2022 Phase 1
NCT04033341 Completed
Healthy
Eli Lilly and Company
 August 1 2019 Phase 1

Chemical Information & Solubility

Molecular Weight 453.56 Formula

C22H27N7O2S
CAS No. 1951483-29-6 SDF Download Temuterkib (LY3214996) SDF
Smiles CC1(C2=C(C=C(S2)C3=NC(=NC=C3)NC4=CC=NN4C)C(=O)N1CCN5CCOCC5)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 27.5 mg/mL ( (60.63 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 15 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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