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Nemtabrutinib (ARQ 531) BTK inhibitor

Name: Nemtabrutinib (ARQ 531)
Brand: Selleck Chemicals
SKU: S8711
Availability: InStock
Rating: 5 (1 reviews)

Cat.No.S8711

An ATP-competitive tyrosine kinase inhibitor, Nemtabrutinib (ARQ 531, MK-1026) is designed to target BTK with an IC50 of 0.85 nM. It also has a distinct kinase selectivity profile with strong inhibitory activity against several key oncogenic drivers from TEC, Trk and Src family kinases.

Chemical Structure

Molecular Weight: 478.93

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Quality Control

Batch: S871101 DMSO]95 mg/mL]false]Ethanol]7 mg/mL]false]Water]Insoluble]false Purity: 99.31%

Cited in Nature Medicine for its top-tier quality
COA
NMR
HPLC
SDS
Datasheet

99.31

Related Targets	EGFR VEGFR JAK PDGFR FGFR Src HIF FLT FLT3 HER2
Other BTK Products	Catadegbrutinib (BGB-16673) Spebrutinib (AVL-292) tirabrutinib(ONO-4059) hydrochloride CGI1746 LFM-A13 CNX-774 BMS-935177 Fenebrutinib (GDC-0853) Branebrutinib (BMS-986195) Evobrutinib

Solubility

In vitro
Batch:

DMSO : 95 mg/mL (198.35 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 7 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.	4.750mg/ml (9.92mM)	Taking the 1 mL working solution as an example, add 50 μL of 95 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.475mg/ml (0.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 9.5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

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

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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	478.93	Formula	C₂₅H₂₃ClN₄O₄	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	2095393-15-8	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	MK-1026			Smiles	C1CC(OCC1NC2=NC=NC3=C2C(=CN3)C(=O)C4=C(C=C(C=C4)OC5=CC=CC=C5)Cl)CO

Mechanism of Action

Targets/IC₅₀/Ki	BTK (Cell-free assay) 0.85 nM BRK (Cell-dree) 2.45 nM BRK (Cell-free assay) 2.45 nM LCK (Cell-free) 3.86 nM LCK (Cell-free assay) 3.86 nM YES (Cell-free) 4.22 nM YES (Cell-free assay) 4.22 nM BMX (Cell-free) 5.23 nM BMX (Cell-free assay) 5.23 nM TEC (Cell-free ) 5.8 nM TEC (Cell-free assay) 5.8 nM BLK (Cell-free assay) 9.71 nM TrkB (Cell-free assay) 11.7 nM TrkA (Cell-free assay) 13.1 nM TrkC (Cell-free) 19.1 nM TrkC (Cell-free assay) 19.1 nM Tie2 (Cell-free assay) 29.4 nM
In vitro	Nemtabrutinib (ARQ 531) potently inhibited BTK (IC50 = 0.85 nM), with the binding potency accompanied by long residence time (51 min). It selectively inhibits BCR signaling dependent PI3K/AKT/mTOR, Ras/Raf/Erk and Rap-GTPase-Cofilin pathways in TMD8 cells. In GCB-DLBCL cell lines (SUDHL-4 and DOHH-2), this compound potently suppressed expression of anti-apoptotic c-Myc and BCL6 oncoproteins in a dose dependent fashion, and concomitantly induced apoptotic cleavage of PARP protein.
In vivo	Nemtabrutinib (ARQ 531) has potent anti-tumor activity, as observed in both ABC-DLBCL and GCB-DLBCL mouse xenograft models. It crosses the blood-brain barrier. In a single oral dose study of 10mg/kg in monkeys, this compound demonstrated a bioavailability of 72.4%, with a Cmax of 9 μM and a half-life greater than 24 hours.
References	[1] https://www.arqule.com/wp-content/uploads/ARQ531_EHA_2017.pdf [2] http://cancerres.aacrjournals.org/content/78/13_Supplement/1963.short [3] http://www.bloodjournal.org/content/128/22/3232?sso-checked=true

Clinical Trial Information

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

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05673460	Active not recruiting	Mature B-cell Neoplasms	Merck Sharp & Dohme LLC	February 13 2023	Phase 1
NCT05347225	Active not recruiting	Hematological Malignancies	Merck Sharp & Dohme LLC	June 9 2022	Phase 1
NCT04728893	Recruiting	Hematologic Malignancies\|Waldenstroms Macroglobulinaemia\|Non-Hodgkins Lymphoma\|Chronic Lymphocytic Leukaemia	Merck Sharp & Dohme LLC	April 5 2021	Phase 2
NCT03162536	Active not recruiting	Lymphoma B-Cell\|Small Lymphocytic Lymphoma\|Chronic Lymphocytic Leukemia\|Waldenstrom Macroglobulinemia\|Mantle Cell Lymphoma\|Diffuse Large B Cell Lymphoma\|Richter''s Transformation\|Follicular Lymphoma\|Marginal Zone Lymphoma	ArQule Inc. a subsidiary of Merck Sharp & Dohme LLC a subsidiary of Merck & Co. Inc. (Rahway NJ USA)	June 26 2017	Phase 1\|Phase 2

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