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| Product Name: | GZD824 | | Synonyms: | Benzamide, 4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]-, methanesulfonate (1:2);4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]-, methanesulfonate (1:2) -Benzamide GZD824 Dimesylate;GZD824 GZD824DIMESYLATE;GZD824 GZD824DIMESYLATE Benzamide, 4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]-, meth;4-Methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]benzamide methanesulfonate (1:2);GZD824DIMESYLATE;CS-1086; Benzamide, 4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]-, methanesulfonate | | CAS: | 1421783-64-3 | | MF: | C31H35F3N6O7S2 | | MW: | 724.7708096 | | EINECS: | | | Product Categories: | Inhibitors | | Mol File: | 1421783-64-3.mol |  |
| | GZD824 Chemical Properties |
| storage temp. | 4°C, away from moisture and light | | solubility | ≥36.25 mg/mL in DMSO; ≥33.95 mg/mL in H2O with ultrasonic; ≥4.71 mg/mL in EtOH with ultrasonic | | form | solid | | color | Light yellow to yellow | | InChIKey | LEVIGHXVOVROGW-UHFFFAOYSA-N |
| | GZD824 Usage And Synthesis |
| Uses | GZD824 is an orally bioavailable Bcr-Abl inhibitor for Bcr-Abl(WT) and Bcr-Abl(T315I). It is a COVID19-related research product. | | Biological Activity | gzd824 is an orally bioavailable inhibitor of bcr-abl with ic50 values of 0.34 and 0.68 nm for bcr-ablwt and bcr-ablt315i, respectively [1].bcr-abl is a fused protein that interacts with the interleukin-3 receptorβ(c) subunit and has tyrosine kinase activity. abl activates cell cycle-related proteins and enzymes and increases cell division. bcr-abl inhibits dna repair and causes genomic instability.gzd824 is an orally bioavailable bcr-abl inhibitor. gzd824 exhibited high affinity with kd values of 0.32 and 0.71 nm for bcr-ablwt and bcr-ablt315i, respectively. gzd824 inhibited bcr-abl with ic50 values of 0.34, 0.68, 0.27, 0.71, 0.15, 0.35, 0.29 and 0.35 nm for bcr-ablwt, bcr-ablt315i, bcr-able255k, bcr-ablg250e, bcr-ablq252h, bcr-ablh396p, bcr-ablm351t and bcr-ably253f, respectively. in a competitive binding assay, gzd824 bound to the atp-binding sites of native abl with kd values of 0.32 and 0.34 nm for non-phosphorylated and phosphorylated abl. in stably transformed ba/f3 cells, gzd824 potently inhibited cells growth with ic50 values of 1.0 and 7.1 nm for bcr-ablwt and bcr-ablt315i expressed cells, respectively [1].in mouse xenograft tumor models, gzd824 inhibited tumor growth. in mice bearing an allograft leukemia model, gzd824 significantly increased survival [1]. | | in vivo | Olverembatinib dimesylate suppresses tumor growth in mice bearing allografted Ba/F3 cells expressing Bcr-AblWT[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-AblT315I[1].
Olverembatinib dimesylate exhibits a good oral bioavailability (rat 48.7%) and Cmax (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].
| Animal Model: | SCID nude mice, bearing allografted Ba/F3 cells expressing Bcr-AblT315I[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%), Cmax (390.5 μg/L), T1/2 (5.6 h). |
| | references | ren x, pan x, zhang z, et al. 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, 56(3): 879-894. |
| | GZD824 Preparation Products And Raw materials |
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