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| | Carbonic acid, (1R,2E,6S,10E,11aS,13S,14aR)-1,6,7,8,9,11a,12,13,14,14a-decahydro-1-hydroxy-6-methyl-4-oxo-4H-cyclopent[f]oxacyclotridecin-13-yl 3-pyridinylmethyl ester 製品概要 |
| 化学名: | | | 英語化学名: | Carbonic acid, (1R,2E,6S,10E,11aS,13S,14aR)-1,6,7,8,9,11a,12,13,14,14a-decahydro-1-hydroxy-6-methyl-4-oxo-4H-cyclopent[f]oxacyclotridecin-13-yl 3-pyridinylmethyl ester | | 别名: | Carbonic acid, (1R,2E,6S,10E,11aS,13S,14aR)-1,6,7,8,9,11a,12,13,14,14a-decahydro-1-hydroxy-6-methyl-4-oxo-4H-cyclopent[f]oxacyclotridecin-13-yl 3-pyridinylmethyl ester;CHNQD-01255 | | CAS番号: | 2756173-91-6 | | 分子式: | C23H29NO6 | | 分子量: | 415.48 | | EINECS: | | | カテゴリ情報: | | | Mol File: | 2756173-91-6.mol | ![Carbonic acid, (1R,2E,6S,10E,11aS,13S,14aR)-1,6,7,8,9,11a,12,13,14,14a-decahydro-1-hydroxy-6-methyl-4-oxo-4H-cyclopent[f]oxacyclotridecin-13-yl 3-pyridinylmethyl ester](CAS/20210305/GIF/2756173-91-6.gif) |
| | Carbonic acid, (1R,2E,6S,10E,11aS,13S,14aR)-1,6,7,8,9,11a,12,13,14,14a-decahydro-1-hydroxy-6-methyl-4-oxo-4H-cyclopent[f]oxacyclotridecin-13-yl 3-pyridinylmethyl ester 物理性質 |
| 沸点 | 648.4±55.0 °C(Predicted) | | 比重(密度) | 1.22±0.1 g/cm3(Predicted) | | 酸解離定数(Pka) | 12.76±0.60(Predicted) |
| | Carbonic acid, (1R,2E,6S,10E,11aS,13S,14aR)-1,6,7,8,9,11a,12,13,14,14a-decahydro-1-hydroxy-6-methyl-4-oxo-4H-cyclopent[f]oxacyclotridecin-13-yl 3-pyridinylmethyl ester Usage And Synthesis |
| 説明 | CHNQD-01255 significantly suppressed tumor growth (TGI = 61.0%) at a dose of 45 mg/kg (p.o.) in the xenograft model. Notably, the improved safety profile of CHNQD-01255 (MTD > 750 mg/kg, p.o.) was confirmed to be superior to that of BFA (MTD < 506 mg/kg). Overall, CHNQD-01255 may serve as a safe and effective new anti-HCC prodrug. | | 使用 | CHNQD-01255 is an orally active Arf-GEFs inhibitor with potent anti-hepatocellular carcinoma (HCC) efficacy[1]. | | in vivo | CHNQD-01255 (5- 45 mg/kg, p.o.) inhibits tumor growth in HepG2 tumor-bearing xenograft mice[1].
CHNQD-01255 exhibits a high safety profile with MTD values exceeding 750 and 100 mg/kg for p.o. and i.p. administrations in mice[1].
| Animal Model: | HepG2 tumor-bearing xenograft mice[1] | | Dosage: | 5, 15, and 45 mg/kg | | Administration: | Oral adminstration (p.o.), every day for 21 consecutive days. | | Result: | Resulted in dramatically delayed tumor progression, with a tumor growth inhibition rate (TGI %) value of 61.0% at 45 mg/kg. |
| Animal Model: | HepG2 tumor-bearing xenograft mice[1] | | Dosage: | 1 and 9 mg/kg | | Administration: | Intraperitoneal injection (i.p.), every day for 21 consecutive days. | | Result: | Inhibited the tumor growth with the TGI values of 36.6 and 48.3%, respectively. |
| Animal Model: | Mice (Pharmacokinetic assay)[1] | | Dosage: | 45 mg/kg p.o., 10 mg/kg i.v. | | Administration: | Oral adminstration (p.o.) or intravenous injection (i.v.) | | Result: | Pharmacokinetic profile of CHNQD-01255.
| dose (mg/kg) | T1/2 (h) | Cmax (ng/mL) | Cl (mL/h/kg) | F (%) | |
| 45 (p.o.) | 7.35 | 20.26 | 598245.37 | 2.26 | |
| 10 (i.v.) | | 2060.78 | | |
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| | 参考文献 | [1] Yao-Yao Jiang, et al. Design and Characterization of a Natural Arf-GEFs Inhibitor Prodrug CHNQD-01255 with Potent Anti-Hepatocellular Carcinoma Efficacy In Vivo. J Med Chem. 2022 Sep 22;65(18):11970-11984. DOI:10.1021/acs.jmedchem.2c00532 |
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