CAS |
914471-09-3 |
English Name |
INCB-024360 |
Synonyms |
4-氨基-N-(3-氯-4-氟苯基)-N'-羟基-1,2,5-恶二唑-3-甲脒 |
Molecular Formula |
C9H7ClFN5O2 |
Molecular Weight |
271.64 |
Solubility |
Soluble in DMSO ≥5mg/mL(Need ultrasonic) |
Purity |
≥98% |
Appearance |
Off-white to yellow Solid |
Storage |
Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year |
MDL |
MFCD18633286 |
SMILES |
ON/C(C1=NON=C1N)=N/C2=CC=C(F)C(Cl)=C2 |
Target Point |
Indoleamine 2,3-Dioxygenase (IDO) |
Passage |
Immunology & Inflammation;Metabolic Enzyme&Protease |
Background |
IDF-11774 is a HIF-1 inhibitor) |
Biological Activity |
IDO5L 是一种有效的吲哚胺-2,3-双加氧酶 (IDO) 抑制剂,IC50 为 67 nM。[1-2] |
IC50 |
IDO:67nM;IDO:19nM(HeLa cell)[1-2] |
In Vitro |
IDO5L(化合物5l)是IDO [1]的有效(HeLa IC50 = 19nM)抑制剂。 IDO5L是IDO1中最有效的抑制剂之一(IC50 = 19 nM,在HeLa细胞检测中)[2]。 |
In Vivo |
在小鼠中测试IDO5L表明IDO的药效学抑制,如通过血浆中的犬尿氨酸水平降低(> 50%)和携带GM-CSF的B16黑素瘤肿瘤的小鼠中的剂量依赖性效力所测量。最初的口服药代动力学研究表明,IDO5L被迅速清除(t1 / 2 <0.5小时),口服给药不适合体内研究。在此期间测量的IDO5L的血浆暴露(2.5μM)超过了我们计算的小鼠蛋白结合调节的B16细胞IC50(PBadjIC50 =1.0μM,鼠细胞B16 IC50 = 46nM)。值得注意的是,4小时后犬尿氨酸水平增加回到基线,因为IDO5L暴露水平从小鼠PBadjIC50降至1.0至0.1μM[1]。 |
Animal Experiment |
小鼠[1]向携带GM-CSF的B16肿瘤的幼稚C57BL / 6小鼠施用单次皮下100mg / kg剂量的IDO5L。在8小时内从个体小鼠收获血液。通过LCMS测量犬尿氨酸和IDO5L浓度。在2和4小时之间观察到犬尿氨酸水平降低50-60%,在2.5小时观察到最大抑制。允许肿瘤生长至第7天,开始以25,50和75mg / kg bid皮下给药IDO5L 14天。剂量依赖性抑制肿瘤生长与血浆中IDO5L的暴露增加相关。 |
Data Literature Source |
[1]. Yue EW,et al. Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model. J Med Chem. 2009 Dec 10;52(23):7364-7. [2]. Huang X,et al. Synthesis of [(18) F] 4-amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide (IDO5L): a novel potential PET probe for imaging of IDO1 expression. J Labelled Comp Radiopharm. 2015 Apr;58(4):156-62 |
Unit |
Bottle |
Specification |
10mg 25mg |