ONO-4059 analogue

Alias: ONO 4059-Analog; ONO-4059-Analog;ONO-WG-307;ONO4059-Analog; GS 4059-Analog; GS-4059-Analog; GS4059-Analog.

Cat No.:V0649 Purity: ≥98%

COA Product Data Instructions for use SDS

ONO-4059 analogue, an analogue of ONO-4059, is a novel, covalent, selective and orally bioavailable BTK inhibitor with potential anticancer and anti-inflammatory activity.

ONO-4059 analogue Chemical Structure CAS No.: 1351635-67-0
Product category: BTK

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of ONO-4059 analogue:

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Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

ONO-4059 analogue, an analogue of ONO-4059, is a novel, covalent, selective and orally bioavailable BTK inhibitor with potential anticancer and anti-inflammatory activity. It inhibits BTK with IC50 of 23.9 nM. ONO-4059 has demonstrated high antitumor activity in several pre-clinical models. It potently and dose-dependently reverse clinical arthritis and prevented bone damage in the CIA model. ONO-4059 inhibited the TMD-8 cell growth and Btk phosphorylation in a concentration-dependent manner. Furthermore, the decrease in Btk phosphorylation subsequently down-regulated Erk phosphorylation. After the combination of ONO-4059 with doxorubicin, etoposide, vincristine and dexamethasone, increased apoptosis ratio was observed, 25, 20, 17 and 29%, respectively.

Biological Activity I Assay Protocols (From Reference)

ln Vitro

In vitro activity: In TMD-8 cells, ONO-4059 inhibits cell growth with IC50 of 3.59 nM, and induces cell apoptosis. The combination of of ONO-4059 with doxorubicin, etoposide, vincristine or dexamethasone causes the increased apoptosis ratio.

Kinase Assay: ONO-4059 analog is the analog of ONO-4059, ONO-4059 is a highly potent and selective Btk inhibitor. IC50 value: sub-nM range.

Cell Assay: ONO-4059 inhibited the TMD-8 cell growth and Btk phosphorylation in a concentration-dependent manner. Furthermore, the decrease in Btk phosphorylation subsequently down-regulated Erk phosphorylation. After the combination of ONO-4059 with doxorubicin, etoposide, vincristine and dexamethasone, increased apoptosis ratio was observed, 25, 20, 17 and 29%, respectively.

ln Vivo

For the 100-200 mm3 tumour groups, tumour growth inhibition at the final treatment day was 23% in QD, 72.9% in BD and 100% in dose mixed in food, groups respectively. For the 400-450 mm3 tumour groups, no growth inhibition was observed in the QD group and, growth inhibitions of 27.5% in BD and 100% in dose mixed in food were observed. The PK concentration and phosphorylated Btk inhibition levels of those animals whose dose was mixed in with food were higher than that of other treatment groups.

Animal Protocol

ONO-4059 has demonstrated anti-tumour activity in several pre-clinical models. ONO-4059 potently and dose-dependently reverse clinical arthritis and prevented bone damage in the CIA model

Mouse tumor and CIA models

References

Blood.2016Jan 28;127(4):411-9.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C25H24N6O3

Molecular Weight

456.50

CAS #

1351635-67-0

Related CAS #

Tirabrutinib;1351636-18-4;Tirabrutinib hydrochloride;1439901-97-9

SMILES

O=C1N([C@H]2CCCN(C(C=C)=O)C2)C3=NC=NC(N)=C3N1C4=CC=C(OC5=CC=CC=C5)C=C4

InChi Key

KSUDUUBCXJUFRL-SFHVURJKSA-N

InChi Code

InChI=1S/C25H24N6O3/c1-2-21(32)29-14-6-7-18(15-29)31-24-22(23(26)27-16-28-24)30(25(31)33)17-10-12-20(13-11-17)34-19-8-4-3-5-9-19/h2-5,8-13,16,18H,1,6-7,14-15H2,(H2,26,27,28)/t18-/m0/s1

Chemical Name

(S)-9-(1-acryloylpiperidin-3-yl)-6-amino-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one

Synonyms

ONO 4059-Analog; ONO-4059-Analog;ONO-WG-307;ONO4059-Analog; GS 4059-Analog; GS-4059-Analog; GS4059-Analog.

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: 20 mg/mL (43.8 mM)

Water:<1 mg/mL

Ethanol:<1 mg/mL

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1906 mL	10.9529 mL	21.9058 mL
	5 mM	0.4381 mL	2.1906 mL	4.3812 mL
	10 mM	0.2191 mL	1.0953 mL	2.1906 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make 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 in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03100942	Completed	Drug: Lanraplenib Drug: Filgotinib	Sjogren's Syndrome	Gilead Sciences	May 1, 2017	Phase 2
NCT02626026	Completed	Drug: Tirabrutinib Drug: Placebo	Rheumatoid Arthritis	Gilead Sciences	January 26, 2016	Phase 1

Biological Data

PFS curves for CLL, MCL, and DLBCL patients. Results are shown for CLL, MCL, and DLBCL patients as separate curves. Estimated mean PFS for each cohort: CLL = 874 days, MCL = 341 days, and DLBCL = 54 days. Blood.2016Jan 28;127(4):411-9.

Efficacy of ONO/GS-4059 in patients with CLL. (A) Duration on treatment for all CLL patients (n = 28) according to dose cohort. *Ongoing patients. (B) Waterfall plot for all CLL patients by dose cohort (n = 25), showing response evaluated by CT imaging. Changes from baseline scan (sum of the largest diameter of each target lesion) are shown. Negative values indicate tumor response. **Patients with TP53/17p deletion; @patients with ATM/11q deletion. (C) Rate of response of lymph nodes in CLL patients up to cycle 7 (n = 23). Measured by the percentage change in tumor SPD. (D) Mean blood concentrations of hemoglobin (g/dL) and platelet count (×109/L) showing recovery of normal hemopoiesis in CLL patients up to cycle 31. (E) Case example: CT axial images from a CLL patient. (i) Pretreatment CT imaging showing large volume intra-abdominal lymphadenopathy. (ii) CT imaging during cycle 3 following treatment with ONO/GS-4059 600 mg once daily shows considerable reduction in lymphadenopathy. SPD, sum of perpendicular dimensions. Blood.2016Jan 28;127(4):411-9.

Efficacy of ONO/GS-4059 in patients with DLBCL. (A) Waterfall plot for all DLBCL patients by dose cohort (n = 17), showing response evaluated by CT imaging. Changes from baseline scan (sum of the largest diameter of each target lesion) are shown. Negative values indicate tumor response. (B) Duration on treatment for all DLBCL patients (n = 35) according to dose cohort. *Ongoing patients. Blood.2016Jan 28;127(4):411-9.