[CAS NO. 1257628-77-5] Olverembatinib
PRODUCTS SPECIFICATIONS [1257628-77-5]
DESCRIPTION [1257628-77-5]
Overview
| MDL | MFCD26142930 |
|---|---|
| Molecular Weight | 532.56 |
| Molecular Formula | C29H27F3N6O |
| 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 |
2 Publications Citing Use of MCE
Summary
Olverembatinib (GZD824) is a potent and orally active pan- Bcr-Abl inhibitor. Olverembatinib potently inhibits a broad spectrum of Bcr-Abl mutants. Olverembatinib strongly inhibits native Bcr-Abl and Bcr-Abl T315I with IC 50 s of 0.34 nM and 0.68 nM, respectively. Olverembatinib 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 shows antiproliferative activity in stably transformed Ba/F3 cells whose growth was driven by native Bcr-Abl or Bcr-Abl mutants
[1]
.
Olverembatinib selectively and potently inhibits the proliferation of Bcr-Abl-positive leukemia cells
[1]
.
Olverembatinib 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 suppresses tumor growth in mice bearing allografted Ba/F3 cells expressing Bcr-Abl
WT
[1]
.
Olverembatinib (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 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 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 |
|---|---|---|---|---|
| NCT04126681 | Ascentage Pharma Group Inc.|HealthQuest Pharma Inc. |
Chronic Myeloid Leukemia, Chronic Phase
|
October 21, 2019 | Phase 2 |
| NCT05594758 | Ascentage Pharma Group Inc.|Tanner Pharma Group |
|
||
| NCT05466175 | Chen Suning|The First Affiliated Hospital of Soochow University |
Philadelphia-Positive ALL
|
October 1, 2022 | Phase 2 |
| NCT03883087 | Ascentage Pharma Group Inc. |
Chronic Myeloid Leukemia, Chronic Phase
|
April 8, 2019 | Phase 2 |
| NCT05521204 | The First Affiliated Hospital of Soochow University |
Myeloproliferative Neoplasm|Acute Leukemia
|
September 1, 2022 | Phase 2 |
| 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 |
| NCT05603156 | Institute of Hematology & Blood Diseases Hospital |
Ph&addition; ALL|Bone Marrow Transplant|Minimal Residual Disease
|
October 30, 2022 | Not Applicable |
| NCT03882281 | Ascentage Pharma Group Inc.|HealthQuest Pharma Inc. |
Chronic Myeloid Leukemia, Chronic Phase
|
March 25, 2019 | Phase 1 |
| NCT05311943 | Shenzhen Second People´s Hospital |
Olverembatinib|Chronic Myeloid Leukemia, Chronic Phase|Tyrosine Kinase Inhibitors
|
July 1, 2022 | Phase 3 |
| 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 |
| 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 |
| NCT03594422 | Ascentage Pharma Group Inc.|HealthQuest Pharma Inc. |
Gastrointestinal Stromal Tumor (GIST)|Solid Tumor, Adult
|
July 11, 2018 | Phase 1 |
| 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 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 41.67 mg/mL ( 78.24 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.8777 mL | 9.3886 mL | 18.7772 mL |
| 5 mM | 0.3755 mL | 1.8777 mL | 3.7554 mL |
| 10 mM | 0.1878 mL | 0.9389 mL | 1.8777 mL |
