[CAS NO. 1439901-97-9] Tirabrutinibhydrochloride

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PRODUCTS SPECIFICATIONS [1439901-97-9]

Catalog

HY-15771A

Brand

MCE

CAS

1439901-97-9

DESCRIPTION [1439901-97-9]

Overview

MDL	-
Molecular Weight	490.94
Molecular Formula	C25H23ClN6O3
SMILES	O=C1N(C2=CC=C(OC3=CC=CC=C3)C=C2)C4=C(N)N=CN=C4N1[C@H]5CN(C(C#CC)=O)CC5.[H]Cl

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

2 Publications Citing Use of MCE

Summary

Tirabrutinib (ONO-4059) hydrochloride is an orally active Bruton’s Tyrosine Kinase ( BTK ) inhibitor (can cross the blood-brain barrier (BBB)), with an IC ₅₀ of 6.8 nM. Tirabrutinib hydrochloride irreversibly and covalently binds to BTK and inhibits aberrant B cell receptor signaling. Tirabrutinib hydrochloride can be used in studies of autoimmune diseases and hematological malignancies ^[1] ^[2] ^[3] ^[4] .

IC50 & Target

BMX

6 nM (IC ₅₀ )

BTK

6.8 nM (IC ₅₀ )

TEC

48 nM (IC ₅₀ )

TXK

92 nM (IC ₅₀ )

BLK

0.3 μM (IC ₅₀ )

ERBB4

0.77 μM (IC ₅₀ )

EGFR

3.02 μM (IC ₅₀ )

JAK3

5.52 μM (IC ₅₀ )

ERBB2

7.31 μM (IC ₅₀ )

In Vitro

Tirabrutinib hydrochloride (0.1-1000 nM or 0.001-100 nM; 72 h) inhibits the proliferation of OCI-L Y10 and SU-DHL-6 cells with IC ₅₀ s of 9.127 nM, and 17.10 nM, respectively ^[1] .
Tirabrutinib hydrochloride (0.5, 5, 50 μM; 24, 48 h) induces SU-DHL-6 cells apoptosis needs high dosage and prolonged administration (concentration up to 50 μM and incubates for 48 h) ^[1] .
Tirabrutinib hydrochloride (300 nM, 72 h) induces caspase-3 and PARP cleavage in TMD8 cells ^[2] .

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

Cell Proliferation Assay ^[1]

Cell Line:	SU-DHL-6 and OCI-L Y10 cells
Concentration:	0.1-1000 nM; 0.001 nM-100 nM.
Incubation Time:	72 h
Result:	Showed good anti-proliferative activity with IC ₅₀ s of 9.127 nM, and 17.10 nM for OCI-L Y10 and SU-DHL-6 cells, respectively.

Apoptosis Analysis ^[1]

Cell Line:	SU-DHL-6 cells
Concentration:	0.5, 5, 50 μM
Incubation Time:	24, 48 h
Result:	Induced cell apoptosis when concentration up to 50 μM and incubated for 48 h.

Western Blot Analysis ^[2]

Cell Line:	TMD8 cells
Concentration:	300 nM
Incubation Time:	72 h
Result:	Induced caspase-3 and PARP cleavage.

In Vivo

Tirabrutinib hydrochloride (10 mg/kg; p.o.; single) is rapidly absorbed into plasma and brain, and reaches C _max (blood C _max =339.53 ng/mL; brain C _max =28.9 ng/mL) 2 hours post administration ^[1] .
Tirabrutinib hydrochloride (6, 20 mg/kg; p.o.; single daily for 3 weeks) shows inhibition of tumour growth in vivo ^[2] .

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

Animal Model:

Male SD rats (219.0–260.5g) ^[1] .

Dosage:

10 mg/kg

Administration:

Oral administration; single.

Result:

1.19 Pharmacokinetic Parameters of Tirabrutinib in male SD rats ^[1] .

	Plasma, C _max (ng/mL)	Brain, C _max (ng/mL)	Penetration rate (%, C _{max, brain} /C _{max, plasma} )
PO (10 mg/kg)	339.53	28.9	8.5

Animal Model:	Immunodeficiency (SCID) mice (mouse xenograft model) ^[2] .
Dosage:	6, 20 mg/kg
Administration:	Oral administration; single daily for 3 weeks.
Result:	Inhibited tumour growth, and when dosage up to 20 mg/kg, a complete tumor suppression at day 14.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase
NCT02626026	Gilead Sciences\|Ono Pharmaceutical Co. Ltd	Rheumatoid Arthritis	January 26, 2016	Phase 1
NCT02457559	Gilead Sciences	Relapsed+Refractory B-cell Malignancies	September 10, 2015	Phase 1
NCT02457598	Gilead Sciences	B-cell Malignancies	June 16, 2015	Phase 1
NCT02968563	Gilead Sciences\|German CLL Study Group	Chronic Lymphocytic Leukemia	December 13, 2016	Phase 2
NCT04827589	Gilead Sciences	Chronic Spontaneous Urticaria	July 2021	Phase 2
NCT01659255	Gilead Sciences\|Ono Pharmaceutical Co. Ltd	Non Hodgkins Lymphoma\|Chronic Lymphocytic Leukaemia	August 17, 2012	Phase 1
NCT03100942	Gilead Sciences\|Galapagos NV\|Ono Pharmaceutical Co. Ltd	Sjogren´s Syndrome	May 1, 2017	Phase 2
NCT04947319	Ono Pharmaceutical Co. Ltd	Part A: Relapsed or Refractory Primary Central Nervous System Lymphoma (PCNSL), Part B: Newly Diagnosed, Treatment naïve PCNSL	December 29, 2021	Phase 2
NCT02983617	Gilead Sciences\|German CLL Study Group	Chronic Lymphocytic Leukemia	April 6, 2017	Phase 2

Appearance

Solid

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture

* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL ( 203.69 mM ; Need ultrasonic)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.0369 mL	10.1845 mL	20.3691 mL
5 mM	0.4074 mL	2.0369 mL	4.0738 mL
10 mM	0.2037 mL	1.0185 mL	2.0369 mL

* Please refer to the solubility information to select the appropriate solvent.

In Vivo:

1.

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

Solubility: 2.5 mg/mL (5.09 mM); Suspended solution; Need ultrasonic
2.

Add each solvent one by one: 10% DMSO >> 90% corn oil

Solubility: ≥ 2.5 mg/mL (5.09 mM); Clear solution
3.

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

Solubility: ≥ 1.79 mg/mL (3.65 mM); Clear solution

* All of the co-solvents are available by MCE.