HG-7-85-01 是一种Bcr-Abl，PDGFRα，Kit和Src激酶的野生型和看门突变形式的 II 型 ATP 竞争性抑制剂。HG-7-85-01 抑制 T315I 突变型 Bcr-Abl (T315I mutant Bcr-Abl) 激酶，KDR和RET，IC50为 3 nM，20 nM 和 30 nM，对其他激酶的抑制作用很小或没有抑制作用 (IC50>2 μM)。HG-7-85-01 通过诱导细胞凋亡 (apoptosis) 和抑制细胞周期进程来抑制细胞增殖。
| 生物活性 | HG-7-85-01 is a type II ATP competitive inhibitor of wild-type and gatekeeper mutations forms ofBcr-Abl,PDGFRα,Kit, andSrckinases. HG-7-85-01 inhibitsT315I mutantBcr-Ablkinase,KDRandRETwithIC50s of 3 nM, 20 nM and 30 nM, and is only weak or no inhibition of other kinases (IC50>2 μM). HG-7-85-01 inhibits the cell proliferation, which is mediated by the induction ofapoptosis, and inhibition of cell-cycle progression[1]. |
| IC50& Target | Bcr-AblT315I 3 nM (IC50) | PDGFRα 440 nM (IC50) | JAK1 120 nM (IC50) | KDR 20 nM (IC50) | RET 30 nM (IC50) | MK5 560 nM (IC50) |
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体外研究
(In Vitro) | HG-7-85-01 (0-1 μM; 24 hours; BCR-ABL-, BCR-ABL-T315I-, Kit-T670I-, PDGFRα-T674M-, and PDGFRα-T674I-expressing cells) treatment leads to G0G1 arrest of BCR-ABL-expressing cells[1].
HG-7-85-01 (0-1 μM; 72 hours; BCR-ABL-, BCR-ABL-T315I-, Kit-T670I-, PDGFRα-T674M-, and PDGFRα-T674I-expressing cells) treatment also leads to induction of apoptosis of BCR-ABL-expressing cells[1].
HG-7-85-01 treatment potently and selectively inhibits the proliferation of 32D- and Ba/F3 cells expressing nonmutant BCR-ABL and the BCR-ABL-T315I gatekeeper mutant. HG-7-85-01 shows higher potency against nonmutant BCR-ABL and BCR-ABL-T315I (IC50= 0.06-0.14 μM)[1].
HG-7-85-01 inhibits BCR-ABL kinase activity in a concentration-dependent manner, suggesting selective targeting of the BCR-ABL kinase as the mechanism of action of HG-7-85-01[1].
HG-7-85-01 potently inhibits the proliferation of Ba/F3 cells expressing the Kit-T670I gatekeeper mutation (Ba/F3- Kit-T670I) and Ba/F3 cells expressing TEL/PDGFRβ and no effect on parental Ba/F3 cells. HG-7-85-01 inhibits Kit, PDGFR phosphorylation in a concentration-dependent manner[1].
The PDGFRα-T674M and PDGFRα-T674I gatekeeper mutant variants are highly responsive to HG-7-85-01 and significant IL-3 rescue[1].
HG-7-85-01 inhibits the proliferation of Ba/F3 cells transformed with human c-Src (EC50= 190 nM), T338I Src (EC50= 290 nM), and T338M Src (EC50= 150 nM; chicken c-Src numbering). And potently inhibits the proliferation of exon 11 Kit mutant-expressing cells, exon 9 kit mutant-expressing cells are significantly less responsive[1].
Cell Cycle Analysis[1] | Cell Line: | BCR-ABL-, BCR-ABL-T315I-, Kit-T670I-, PDGFRα-T674M-, and PDGFRα-T674I-expressing cells | | Concentration: | 0 μM, 0.01 μM, 0.1 μM and 1 μM | | Incubation Time: | 24 hours | | Result: | Led to G0G1 arrest of BCR-ABL-expressing cells. |
Apoptosis Analysis[1] | Cell Line: | BCR-ABL-, BCR-ABL-T315I-, Kit-T670I-, PDGFRα-T674M-, and PDGFRα-T674I-expressing cells | | Concentration: | 0 μM, 0.01 μM, 0.1 μM and 1 μM | | Incubation Time: | 72 hours | | Result: | Led to induction of apoptosis of BCR-ABL-expressing cells. |
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体内研究
(In Vivo) | HG-7-85-01 has limited oral bioavailability (BAV % F mouse = 5 %, rat = 19 %), a moderate half life (T1/2mouse =1.1 h rat = 5.8 hours), a relative low maximal serum concentration (Cmaxmouse = 106 ng/mL at 10 mg/kg , rat = 292 ng/mL and 2 mg/kg ) and a relatively high clearance (Cl mouse = 23 ml/min/kg, rat = 13 ml/min/kg)[1].
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
