| Identification | Back Directory | [Name]
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]
2756173-91-6 | [Synonyms]
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 | [Molecular Formula]
C23H29NO6 | [MOL File]
2756173-91-6.mol | [Molecular Weight]
415.48 |
| Hazard Information | Back Directory | [Description]
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. | [Uses]
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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| [References]
[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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