AC710 mesylate, the mesylate salt of AC710, is a potent, orally bioactive, and selective inhibitor of PDGFR (platelet-derived growth factor receptor) family kinase with Kd values of 0.6, 1.57, 1, 1.3, 1.0 nM for FLT3, CSF1R, KIT, PDGFRα and PDGFRβ, respectively. As a PDGFR inhibitor, AC710 has potential anticancer activity. Results from a mouse tumor xenograft, a collagen-induced arthritis model, and a 7 day rat in vivo tolerability study culminated in the selection of AC710 as a preclinical development candidate.
理化性质和储存条件
| Molecular Weight (MW) | 658.81 |
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| Formula | C32H46N6O7S |
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| CAS No. | 1351522-05-8 (mesylate); |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 10 mM |
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| Water: <1 mg/mL |
| Ethanol: N/A |
| Solubility (In vivo) | O=C(C1=NC=C(OC2CC(C)(C)N(CC)C(C)(C)C2)C=C1)NC3=CC=C(NC(NC4=NOC(C(C)(C)C)=C4)=O)C=C3. CS(=O)(O)=O |
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| Synonyms | AC 710 Mesylate; AC710 Mesylate; AC-710 Mesylate. |
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实验参考方法
| In Vitro | In vitro activity: AC710 is a potent, orally active, and selective inhibitor of PDGFR (platelet-derived growth factor receptor) family kinase with Kd values of 0.6, 1.57, 1, 1.3, 1.0 nM for FLT3, CSF1R, KIT, PDGFRα and PDGFRβ, respectively. As a PDGFR inhibitor, AC710 has potential anticancer activity. Results from a mouse tumor xenograft, a collagen-induced arthritis model, and a 7 day rat in vivo tolerability study culminated in the selection of AC710 as a preclinical development candidate.
Kinase Assay: AC710 is a potent, orally active, and selective inhibitor of PDGFR (platelet-derived growth factor receptor) family kinase with Kd values of 0.6, 1.57, 1, 1.3, 1.0 nM for FLT3, CSF1R, KIT, PDGFRα and PDGFRβ, respectively. |
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| In Vivo | At 0.3 mg/kg of AC710, tumor growth is temporally inhibited, and growth resumes quickly thereafter. At 3 and 30 mg/kg of AC710, tumors regress completely, and the tumor volume stays suppressed for an extended period after dosing is halted. No body weight loss is observed in animals treated with AC710 at all doses, indicating that it is well tolerated in mice at efficacious doses. AC710 exhibits a significant impact on disease in a dose-dependent fashion in a mouse collagen-induced arthritis (CIA) model, at a dose as low as 3 mg/ kg for 15 days (day 0-14). At 10 and 30 mg/kg, AC710 demonstrates equivalent or slightly better efficacy in reducing the joint swelling and inflammation than dexomethasone administered at a safe dose. AC710 is well tolerated at the tested doses |
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| Animal model | Athymic nude mice models with subcutaneous flank-tumor xenograft model using the MV4-11cell line |
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| Formulation & Dosage | 0.3, 3, and 30 mg/kg |
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| References | ACS Med Chem Lett. 2012 Sep 24;3(12):997-1002 |
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