| Identification | Back Directory | [Name]
1(2H)-Isoquinolinone, 2-[(S)-cyclopropyl(4-methyl-2-pyridinyl)methyl]-5-[1-ethyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-3,4-dihydro-7-(1H-imidazol-1-ylmethyl)- | [CAS]
2417012-26-9 | [Synonyms]
WDR5-IN-5
WDR5 inhibitor 41
1(2H)-Isoquinolinone, 2-[(S)-cyclopropyl(4-methyl-2-pyridinyl)methyl]-5-[1-ethyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-3,4-dihydro-7-(1H-imidazol-1-ylmethyl)- | [Molecular Formula]
C29H29F3N6O | [MOL File]
2417012-26-9.mol | [Molecular Weight]
534.58 |
| Chemical Properties | Back Directory | [Boiling point ]
752.8±60.0 °C(Predicted) | [density ]
1.39±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
6.63±0.12(Predicted) | [color ]
White to light yellow |
| Hazard Information | Back Directory | [Uses]
WDR5-IN-5 is an orally active and selective inhibitor of WIN site of WD repeat domain 5 (WDR5). WDR5-IN-5 exhibits anti-proliferative activity towards cancer cells and good pharmacokinetics profile in mice. WDR5-IN-5 shows high affinity to WDR5 and the binding affinity Ki value <0.02 nM[1]. | [in vivo]
WDR5-IN-5 (compound 41) (10 mg/kg; p.o.) shows high oral exposure (AUC0,inf=3984 h.ng/mL), long half-life of T1/2=1.3 h[1].
WDR5-IN-5 (3 mg/kg; i.v.) also shows low iv clearance (26 mL/min/kg). WDR5-IN-5 is well tolerated and shows no adverse effects in mice by both i.v. and p.o. dosing[1].
WDR5-IN-5 can be formulated as 0.6 and 1 mg/mL solutions in ethanol, tocopherol poly (ethylene glycol) succinate (TPGS), PEG400 and water (v/v/v/v, 5/5/30/60) for i.v. and p.o. dosing, respectively[1].
PK profile of WDR5-IN-5 in CD-1 Mice[1]
| Route | Dose (mg/kg) | CL (mL/min/kg) | AUC0,inf (h.ng/mL) | Vss (L/kg) | T1/2 (h) | F (%) | | i.v. | 3 | 26 | 1951 | 1.6 | / | / | | p.o. | 10 | 2083 | 3984 | / | 1.3 | 61 |
| Animal Model: | Male CD-1 mice[1] | | Dosage: | 3 mg/kg i.v.; 10 mg/kg p.o. | | Administration: | Intravenous injection or oral gavage | | Result: | Showed high oral exposure (AUC0,inf=3984 h.ng/mL), long half-life of T1/2=1.3 h, and low iv clearance (26 mL/min/kg). |
| [References]
[1] Teuscher KB, et al. Discovery of Potent Orally Bioavailable WD Repeat Domain 5 (WDR5) Inhibitors Using a Pharmacophore-Based Optimization. J Med Chem. 2022 Apr 28. 65(8):6287-6312. DOI:10.1021/acs.jmedchem.2c00195 |
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