2. Protein Tyrosine Kinase/RTK
  3. Btk
  4. Nemtabrutinib

Nemtabrutinib  (Synonyms: ARQ-531; MK-1026)

Cat. No.: HY-112215 Purity: 99.32%
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COA
Handling Instructions Technical Support

Nemtabrutinib (ARQ 531) is a reversible non-covalent and orally active inhibitor of Bruton’s Tyrosine Kinase (BTK), with IC50s of 0.85 nM and 0.39 nM for WT-BTK and C481S-BTK, respectively.

For research use only. We do not sell to patients.

Nemtabrutinib Chemical Structure

Nemtabrutinib Chemical Structure

CAS No. : 2095393-15-8

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10 mM * 1 mL in DMSO
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Customer Review

Based on 3 publication(s) in Google Scholar

Nemtabrutinib Related Antibodies

Top Publications Citing Use of Products

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

Nemtabrutinib (ARQ 531) is a reversible non-covalent and orally active inhibitor of Bruton’s Tyrosine Kinase (BTK), with IC50s of 0.85 nM and 0.39 nM for WT-BTK and C481S-BTK, respectively.

IC50 & Target

IC50: 0.85 nM (WT-BTK), 0.39 nM (C481S-BTK)[1].
In Vitro

Nemtabrutinib (ARQ 531) shows strong target inhibition in TMD8 cell line. The IC50 values are 0.85 nM and 0.39 nM for WT-BTK and C481S-BTK, respectively, in biochemical assay. Additionally, Nemtabrutinib also shows strong inhibition of TEK kinases with IC50s of 5.23 nM (BMX), 5.80 nM (TEC), 36.4 nM (TXK). The IC50s of Nemtabrutinib for SRC kinases are 3.86 nM (LCK), 4.22 nM (YES), 9.71 nM (BLK), 18.3 nM (HCK), 18.8 nM (LYNa), 25.9 nM (FGR), 32.2 nM (FYN), 48.0 nM (FRK) and for TRK kinases are 11.7 nM (TrkB), 13.1 nM (TrkA), 19.1 nM (TrkC). Nemtabrutinib inhibits proliferation of diverse types of cell lines (TMD8: GI50=0.13 μM, REC1: GI50=0.18 nM) and shows potency in cell lines that are addict to BCR, Src-family kinase and PI3K/AKT pathways.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Nemtabrutinib Related Antibodies
In Vivo

Nemtabrutinib is efficacious in TMD-8 tumor xenograft model. Nemtabrutinib causes complete tumor regression after 14 days of treatment. Nemtabrutinib is also efficacious in collagen induced arthritis model. Nemtabrutinib demonstrates potent efficacy against arthritis in mouse model. In the BTK driven TMD8 xenograft mouse model, Nemtabrutinib demonstrates excellent anti-tumor activity with durable response. Nemtabrutinib demonstrates in vivo efficacy in a mouse collagen-induced arthritis (CIA) model[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Molecular Weight

478.93

Formula

C25H23ClN4O4
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

O=C(C1=C(C=C(OC2=CC=CC=C2)C=C1)Cl)C3=CNC4=NC=NC(N[C@@H]5CC[C@@H](CO)OC5)=C34
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : ≥ 50 mg/mL (104.40 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.0880 mL 10.4399 mL 20.8799 mL
5 mM 0.4176 mL 2.0880 mL 4.1760 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

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Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.08 mg/mL (4.34 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.08 mg/mL (4.34 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.32%

SDS (393 KB)

COA (246 KB) HNMR (284 KB) LCMS (98 KB)

Handling Instructions (2659 KB)
References
Cell Assay
[1]

Biochemical inhibition assay is measured using full length BTK constructs of wild type or C481S mutant. Profiling on 236 kinases identifies 45 kinases with >50% inhibition at 200 nM concentration of ARQ 531. Subsequently, the potency of this ATP competitive inhibitor is determined on such kinases at the physiological 1 mM ATP concentration cells are treated with increasing concentrations of inhibitors in SUDHL-4 for 2 hours, following stimulation with either anti-IgM or growth factors cells are lysed for Western blot analysis[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Mice[1]
Six week old female CB-17 SCID mice (1-2 weeks) are used. Mice are housed in sterile micro isolator cages, five mice per cage and receive food and water ad libitum. Female SCID mice are implanted subcutaneously with 8x106 TMD8 cells in 0.2 mL HBSS with 50% standard concentration BD matrigel in the upper right flank area. Mice are monitored and staged on day 14 (post injection of tumor cells) when size reaches approximately 400 mg. Oral daily dosing with ARQ 531 at 100 mg/kg or vehicle began on stage day. Tumor measurements and body weights are collected three times a week. In vivo Target and pathway inhibition is studied in mouse TMD8 xenograft model. Percent inhibition relative to the vehicle control is determined using densitometry analysis and the intensity of actin band is used as a loading control and the percentage of vehicle group is designated as 100%. DBA1/J mice are immunized with collagen to develop the arthritis, following the onset of arthritis, mice are randomized into treatment groups. Treatment is initiated by oral dosing of ARQ 531 at 25, 50 and 75 mg/kg and continued daily through arthritis day 14. Clinical scores are assessed for each of the paws on study arthritis days 1-15[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.0880 mL 10.4399 mL 20.8799 mL 52.1997 mL
5 mM 0.4176 mL 2.0880 mL 4.1760 mL 10.4399 mL
10 mM 0.2088 mL 1.0440 mL 2.0880 mL 5.2200 mL
15 mM 0.1392 mL 0.6960 mL 1.3920 mL 3.4800 mL
20 mM 0.1044 mL 0.5220 mL 1.0440 mL 2.6100 mL
25 mM 0.0835 mL 0.4176 mL 0.8352 mL 2.0880 mL
30 mM 0.0696 mL 0.3480 mL 0.6960 mL 1.7400 mL
40 mM 0.0522 mL 0.2610 mL 0.5220 mL 1.3050 mL
50 mM 0.0418 mL 0.2088 mL 0.4176 mL 1.0440 mL
60 mM 0.0348 mL 0.1740 mL 0.3480 mL 0.8700 mL
80 mM 0.0261 mL 0.1305 mL 0.2610 mL 0.6525 mL
100 mM 0.0209 mL 0.1044 mL 0.2088 mL 0.5220 mL
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Nemtabrutinib Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Nemtabrutinib2095393-15-8ARQ-531 MK-1026ARQ531ARQ 531MK1026MK 1026MK-1026BtkBruton tyrosine kinaseInhibitorinhibitorinhibit

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