[CAS NO. 1421783-64-3] Olverembatinibdimesylate

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PRODUCTS SPECIFICATIONS [1421783-64-3]

Catalog

HY-15666A

Brand

MCE

CAS

1421783-64-3

DESCRIPTION [1421783-64-3]

Overview

MDL	-
Molecular Weight	724.77
Molecular Formula	C31H35F3N6O7S2
SMILES	O=C(NC1=CC=C(CN2CCN(C)CC2)C(C(F)(F)F)=C1)C3=CC=C(C)C(C#CC4=CN=C(NN=C5)C5=C4)=C3.CS(=O)(O)=O.CS(=O)(O)=O

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

2 Publications Citing Use of MCE

Summary

Olverembatinib (GZD824) dimesylate is a potent and orally active pan- Bcr-Abl inhibitor. Olverembatinib dimesylate potently inhibits a broad spectrum of Bcr-Abl mutants. Olverembatinib dimesylate strongly inhibits native Bcr-Abl and Bcr-Abl ^T315I with IC ₅₀ s of 0.34 nM and 0.68 nM, respectively. Olverembatinib dimesylate has antitumor activity ^[1] .

IC50 & Target

IC50: 0.68 nM (Bcr-Abl ^T315I ), 0.27 nM (Bcr-Abl ^E255K ) , 0.71 nM (Bcr-Abl ^G250E ) , 0.15 nM (Bcr-Abl ^Q252H ), 0.35 nM (Bcr-Abl ^H396P ), 0.29 nM (Bcr-Abl ^M351T ), 0.35 nM (Bcr-Abl ^Y253F ), Bcr-Abl ^F317L ^[1]

In Vitro

Olverembatinib dimesylate shows antiproliferative activity in stably transformed Ba/F3 cells whose growth was driven by native Bcr-Abl or Bcr-Abl mutants ^[1] .
Olverembatinib dimesylate selectively and potently inhibits the proliferation of Bcr-Abl-positive leukemia cells ^[1] .
Olverembatinib dimesylate inhibits Bcr-Abl signaling in K562 (1-20 nM; 4.0 hours) and Ba/F3 stable cell lines expressing native Bcr-Abl (0.1-100 nM; 4.0 hours) or Bcr-Abl ^T315I (0.1-100 nM; 4.0 hours) ^[1] .

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

Western Blot Analysis ^[1]

Cell Line:	K562 cells
Concentration:	1 nM, 2 nM, 5 nM, 10 nM, 20nM
Incubation Time:	4.0 hours
Result:	Inhibited Bcr-Abl signaling in K562 cell lines.

In Vivo

Olverembatinib dimesylate suppresses tumor growth in mice bearing allografted Ba/F3 cells expressing Bcr-Abl ^WT ^[1] .
Olverembatinib dimesylate (1-20 mg/kg; i.g.; daily; for 10 days) significantly increases the median survival of the mice bearing allografted Ba/F3 cells expressing Bcr-Abl ^T315I ^[1] .
Olverembatinib dimesylate exhibits a good oral bioavailability (rat 48.7%) and C _max (rat 390.5 μg/L) following oral administration (rat; 25 mg/kg) ^[1] .
Olverembatinib dimesylate exhibits terminal elimination half-lives (rat 5.6 h) due to high plasma clearance (rat 1.7 L/h/kg) following intravenous administration (rat 5 mg/kg) ^[1] .

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

Animal Model:	SCID nude mice, bearing allografted Ba/F3 cells expressing Bcr-Abl ^T315I ^[1]
Dosage:	1 mg/kg, 2 mg/kg, 5.0 mg/kg, 10 mg/kg, 20 mg/kg
Administration:	Oral gavage, daily, for 10 days
Result:	Efficiently prolonged animal survival in an allograft leukemia tumor model.

Animal Model:	Rats ^[1]
Dosage:	5 mg/kg for i.v.; 25 mg/kg for oral (Pharmacokinetic Analysis)
Administration:	Intravenous injection and oral administration
Result:	Oral bioavailability (48.7%), C _max (390.5 μg/L), T _1/2 (5.6 h).

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase
NCT03883087	Ascentage Pharma Group Inc.	Chronic Myeloid Leukemia, Chronic Phase	April 8, 2019	Phase 2
NCT05594758	Ascentage Pharma Group Inc.\|Tanner Pharma Group
NCT04126707	Ascentage Pharma Group Inc.\|HealthQuest Pharma Inc.	Chronic Myeloid Leukemia (CML)	November 19, 2019	Phase 1
NCT05594784	Institute of Hematology & Blood Diseases Hospital	Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia	October 8, 2022	Phase 2
NCT03594422	Ascentage Pharma Group Inc.\|HealthQuest Pharma Inc.	Gastrointestinal Stromal Tumor (GIST)\|Solid Tumor, Adult	July 11, 2018	Phase 1
NCT05521204	The First Affiliated Hospital of Soochow University	Myeloproliferative Neoplasm\|Acute Leukemia	September 1, 2022	Phase 2
NCT03882281	Ascentage Pharma Group Inc.\|HealthQuest Pharma Inc.	Chronic Myeloid Leukemia, Chronic Phase	March 25, 2019	Phase 1
NCT05603156	Institute of Hematology & Blood Diseases Hospital	Ph&addition; ALL\|Bone Marrow Transplant\|Minimal Residual Disease	October 30, 2022	Not Applicable
NCT04260022	Ascentage Pharma Group Inc.	Leukemia, Myeloid, Chronic\|Myeloid Leukemia\|Chronic Myeloid Leukemia\|Philadelphia Positive Acute Lymphoblastic Leukemia\|B Cell Precursor Type Acute Leukemia	January 9, 2020	Phase 1
NCT05466175	Chen Suning\|The First Affiliated Hospital of Soochow University	Philadelphia-Positive ALL	October 1, 2022	Phase 2
NCT04126681	Ascentage Pharma Group Inc.\|HealthQuest Pharma Inc.	Chronic Myeloid Leukemia, Chronic Phase	October 21, 2019	Phase 2
NCT05604755	xuna\|Nanfang Hospital of Southern Medical University\|Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University\|Third Affiliated Hospital, Sun Yat-Sen University\|Guangdong Second Provincial General Hospital	Prophylactic HQP1351 Therapy\|Third Generation TKI	January 1, 2022	Phase 2
NCT03883100	Ascentage Pharma Group Inc.	Chronic Myeloid Leukemia - Accelerated Phase	April 8, 2019	Phase 2
NCT05376852	Nanfang Hospital of Southern Medical University	Chronic Myeloid Leukemia in Myeloid Blast Crisis\|Chronic Myeloid Leukaemia Transformation\|Chronic Myeloid Leukemia - Accelerated Phase\|Chronic Myeloid Leukemia in Lymphoid Blast Crisis (Diagnosis)	December 1, 2021	Phase 2
NCT05311943	Shenzhen Second People´s Hospital	Olverembatinib\|Chronic Myeloid Leukemia, Chronic Phase\|Tyrosine Kinase Inhibitors	July 1, 2022	Phase 3

Appearance

Solid

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture and light

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

Solvent & Solubility

In Vitro:

DMSO : 125 mg/mL ( 172.47 mM ; Need ultrasonic)

H ₂ O : ≥ 50 mg/mL ( 68.99 mM )

* "≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.3797 mL	6.8987 mL	13.7975 mL
5 mM	0.2759 mL	1.3797 mL	2.7595 mL
10 mM	0.1380 mL	0.6899 mL	1.3797 mL

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

In Vivo:

1.

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

Solubility: ≥ 2.08 mg/mL (2.87 mM); Clear solution
2.

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

Solubility: ≥ 2.08 mg/mL (2.87 mM); Clear solution
3.

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

Solubility: ≥ 2.08 mg/mL (2.87 mM); Clear solution

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

References

[1] Ren X, Pan X, Zhang Z, Identification of GZD824 as an orally bioavailable inhibitor that targets phosphorylated and nonphosphorylated breakpoint cluster region-Abelson (Bcr-Abl) kinase and overcomes clinically acquired mutation-induced resistance against