Nemtabrutinib (ARQ 531)

Catalog No.S8711 Batch:S871101

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Technical Data

Formula

C25H23ClN4O4
Molecular Weight 478.93 CAS No. 2095393-15-8
Solubility (25°C)* In vitro DMSO 95 mg/mL (198.35 mM)
Ethanol 7 mg/mL (14.61 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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)		 View More
0.85 nM 2.45 nM 2.45 nM 3.86 nM 3.86 nM
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].
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].

Protocol (from reference)

Cell Assay:

[3]
  • Cell lines

    CLL cells

  • Concentrations

    0.1 μM, 1.0 μM, or 10.0 μM

  • Incubation Time

    72 h

  • Method

    --
Animal Study:

[3]
  • 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

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

BTK inhibition sensitizes Acute Lymphoblastic Leukemia to asparaginase by suppressing the Amino Acid Response pathway [ Blood, 2021, blood.2021011787] PubMed: 34280258

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.