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

Nemtabrutinib (ARQ 531, MK-1026) is an ATP-competitive tyrosine kinase inhibitor 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.

Nemtabrutinib (ARQ 531) Chemical Structure

CAS: 2095393-15-8

Selleck's Nemtabrutinib (ARQ 531) has been cited by 1 publication

Purity & Quality Control

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

99.31

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Signaling Pathway

BTK Signaling Pathway

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Biological Activity

Description

Nemtabrutinib (ARQ 531, MK-1026) is an ATP-competitive tyrosine kinase inhibitor 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.

Targets

BTK ^[1] (Cell-free assay)	BRK ^[1] (Cell-dree)	BRK ^[1] (Cell-free assay)	LCK ^[1] (Cell-free)	LCK ^[1] (Cell-free assay)	Click to View More Targets
0.85 nM	2.45 nM	2.45 nM	3.86 nM	3.86 nM	Click to View More Targets

In vitro
In vitro	ARQ 531 potently inhibited BTK (IC50 = 0.85 nM), the binding potency was accompanied by long residence time (51 min). ARQ 531 selectively inhibits BCR signaling dependent PI3K/AKT/mTOR, Ras/Raf/Erk and Rap-GTPase-Cofilin pathways in TMD8 cells. It potently inhibits proliferation of hematological malignant cell lines both sensitive and resistant to ibrutinib addicted to BCR signaling^[1]. Unlike ibrutinib, ARQ 531 suppressed both the upstream activating signals (via inhibition of a select member of Src kinase family) and the downstream signaling pathways (via pAKT and pERK kinases). In GCB-DLBCL cell lines (SUDHL-4 and DOHH-2), ARQ 531 potently suppressed expression of anti-apoptotic c-Myc and BCL6 oncoproteins in a dose dependent fashion, and concomitantly induced apoptotic cleavage of PARP protein^[2].
Cell Research	Cell lines	CLL cells
	Concentrations	0.1 μM, 1.0 μM, or 10.0 μM
	Incubation Time	72 h
	Method	--

In Vivo
In vivo	ARQ 531 has potent anti-tumor activity was observed in both ABC-DLBCL and GCB-DLBCL mouse xenograft models^[1]. ARQ 531 crosses the blood, brain-barrier^[2]. In a single oral dose study of 10mg/kg in monkeys, the bioavailability of ARQ 531 is 72.4% with a Cmax of 9 μM and a half-life greater than 24 hours^[3].
Animal Research	Animal Models	B6 mice engrafted with 1E7 CD5+/CD19+ TCL1 lymphocytes via tail vein injection
	Dosages	50 or 75 mg/kg
	Administration	by oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT05673460	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

References

Chemical Information & Solubility

Molecular Weight	478.93	Formula	C₂₅H₂₃ClN₄O₄
CAS No.	2095393-15-8	SDF	--
Smiles	C1CC(OCC1NC2=NC=NC3=C2C(=CN3)C(=O)C4=C(C=C(C=C4)OC5=CC=CC=C5)Cl)CO
Storage (From the date of receipt)	3 years -20°C powder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years -20°C powder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 95 mg/mL ( (198.35 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 7 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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