WDR5-IN-5 是一种具有口服活性和选择性、靶向 WD 重复结构域 5 (WDR5)WIN位点的抑制剂。WDR5-IN-5 对WDR5具有高亲和力，结合亲和力 Ki<0.02 nM。WDR5-IN-5 具有抗癌细胞增殖活性和良好的药代动力学特征。

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 K i value<0.02 nM [1].

WDR5 plays an important role in the activity of MLL1 histone methyltransferase (HMT) complexes. WDR5-IN-5 (compound 41), as a WDR5 inhibitor, will exihibits inhibitory effect towards HMT [1]. WDR5-IN-5 displays average soluble concentrations (kinetic solubility) of 60 μM [1]. WDR5-IN-5 exhibits high selectivity between K562 cells and MV4:11, the selectivity index (GI 50, K562 /GI 50, MV4:11 ) is 290 [1]. WDR5-IN-5 (0-30 μM; 5 d) inhibits cell proliferation of MV4:11, MOLM-13, and K562 with GI 50 values are 13, 27, 3700 nM, respectively [1]. Cell Proliferation Assay [1] Cell Line: MV4:11, MOLM-13 cells Concentration: 0-30 μM Incubation Time: 5 days Result: Inhibited cell growth of MV4:11, MOLM-13, and showed on- and off-target inhibition mechanism.

WDR5-IN-5 (compound 41) (10 mg/kg; p.o.) shows high oral exposure (AUC 0,inf =3984 h. ng/mL), long half-life of T 1/2 =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) AUC 0,inf (h. ng/mL) V ss (L/kg) T 1/2 (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 (AUC 0,inf =3984 h.ng/mL), long half-life of T 1/2 =1.3 h, and low iv clearance (26 mL/min/kg).

2417012-26-9

C29H29F3N6O

534.58

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years