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LY3214996 (Temuterkib) ERK1/2 Inhibitor

Name: LY3214996 (Temuterkib)
Brand: Selleck Chemicals
SKU: S8534
Availability: InStock
Rating: 5 (62 reviews)

Cat.No.S8534

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.

Chemical Structure

Molecular Weight: 453.56

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Quality Control

Batch: Purity: 99.91%

99.91

Related Targets	p38 MAPK Raf JNK MEK Ras KRas S6 Kinase MAP4K TAK1 Mixed Lineage Kinase
Other ERK Inhibitors	Ravoxertinib (GDC-0994) Ulixertinib (BVD-523) SCH772984 FR 180204 VX-11e XMD8-92 AZD0364 (ATG-017) ERK5-IN-1 Senkyunolide I MK-8353 (SCH900353)

Solubility

In vitro
Batch:

DMSO : 27.5 mg/mL (60.63 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 15 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.000mg/ml (6.61mM)	Taking the 1 mL working solution as an example, add 50 μL 60 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	453.56	Formula	C₂₂H₂₇N₇O₂S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1951483-29-6	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1(C2=C(C=C(S2)C3=NC(=NC=C3)NC4=CC=NN4C)C(=O)N1CCN5CCOCC5)C

Mechanism of Action

Targets/IC₅₀/Ki	ERK1 (Cell-free assay) 5 nM ERK2 (Cell-free assay) 5 nM
In vitro	Temuterkib (LY3214996) possesses an optimal balance of potency (hERK1 IC50 5 nM, hERK2 IC50 5nM, pRSK IC50 0.43 µM) and solubility. 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 this compound.
In vivo	In tumor xenograft models, Temuterkib (LY3214996) inhibits PD biomarker phospho-p90RSK1 in tumors and the PD effects are correlated with compound exposures and anti-tumor activities. It 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 this compound as a single agent 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, it 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, it can be combined with investigational and approved agents in preclinical models, particularly KRAS mutant models. Combination treatment with a 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. This compound 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.
References	[1] http://cancerres.aacrjournals.org/content/77/13_Supplement/4973 [2] https://www.researchgate.net/publication/318810417 [3] https://pubmed.ncbi.nlm.nih.gov/35764642/ [4] https://pubmed.ncbi.nlm.nih.gov/36384095/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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