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Purity: ≥98%
Olverembatinib Dimesylate (GZD-824; HQP-1351; trade name in China: Nailike), the dimesylate salt of GZD824 (HQP1351), is a novel, potent, orally bioavailable Bcr-Abl inhibitor with potential antineoplastic activity. As of November 2021, Olverembatinib has been approved in China for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation. It inhibits Bcr-Abl(WT) and Bcr-Abl(T315I) with IC50s of 0.34 nM and 0.68 nM, respectively.
| ln Vitro |
In stably transformed Ba/F3 cells, Olverembatinib dimesylate shows antiproliferative activity, with growth driven by either native Bcr-Abl or Bcr-Abl mutants [1]. Leukemia cells positive for Bcr-Abl[1]. 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–AblT315I (0.1–100 nM; 4.0 hours), olverembatinib dimesylate inhibits Bcr–Abl signaling[1].
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| ln Vivo |
In mice bearing allogeneic Ba/F3 cells expressing Bcr-AblWT, olverembatinib dimesylate reduces tumor growth[1]. The median lifespan of mice harboring allogeneic Ba/F3 cells expressing Bcr-AblT315I is markedly increased by olverembatinib dimesylate (1–20 mg/kg; ig; daily; for 10 days) [1]. Olverembatinib dimesylate, when administered orally to rats at a dose of 25 mg/kg, demonstrates a good oral bioavailability (rats 48.7%) and Cmax (rats 390.5 μg/L) [1]. Because of its high plasma clearance (1.7 L/h/kg) upon intravenous dosing (rat 5 mg/kg), olverembatinib dimesylate has a terminal elimination half-life (rat 5.6 hours) [1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: K562 cells Tested Concentrations: 1 nM, 2 nM, 5 nM, 10 nM, 20nM Incubation Duration: 4.0 hrs (hours) Experimental Results: Inhibited Bcr-Abl signaling in K562 cell lines. |
| Animal Protocol |
Animal/Disease Models: SCID nude mice, bearing allografted Ba/F3 cells expressing Bcr-AblT315I[1]
Doses: 1 mg/kg, 2 mg/kg, 5.0 mg/kg, 10 mg/kg, 20 mg/kg Route of Administration: po (oral gavage) , daily, for 10 days Experimental Results: Efficiently prolonged animal survival in an allograft leukemia tumor model. Animal/Disease Models: Rats[1] Doses: 5 mg/kg for iv; 25 mg/kg for oral (pharmacokinetic/PK Analysis) Route of Administration: intravenous (iv) injection and oral administration Experimental Results: Oral bioavailability (48.7%), Cmax (390.5 μg/L), T1/2 (5.6 h). |
| 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 imatinib. J Med Chem. 2013 Feb 14;56(3):879-94.
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| Molecular Formula |
C29H27F3N6O.2CH4O3S
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| Molecular Weight |
724.77
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| CAS # |
1421783-64-3
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| Related CAS # |
Olverembatinib;1257628-77-5
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| SMILES |
CC1C=CC(C(NC2C=CC(CN3CCN(C)CC3)=C(C(F)(F)F)C=2)=O)=CC=1C#CC1C=NC2NN=CC=2C=1.CS(O)(=O)=O.CS(O)(=O)=O
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Preparing Stock Solutions | 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 |
*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.
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.
(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.
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