914471-09-3
914471-09-3 structure
- Name: INCB024360 analogue
- Chemical Name: 4-Amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3 -carboximidamide
- CAS Number: 914471-09-3
- Molecular Formula: C9H7ClFN5O2
- Molecular Weight: 271.636
- Catalog: Biochemical Inhibitor Metabolism IDO inhibitor
- Create Date: 2016-06-15 02:05:21
- Modify Date: 2024-01-03 23:44:48
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IDO5L is a potent indoleamine 2,3-dioxygenase (IDO) inhibitor with an IC50 of 67 nM.
| Name | 4-Amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3 -carboximidamide |
|---|---|
| Synonyms |
IDO inhibitor 1
4-amino-N-(2-thioxo-2,3-dihydro-benzooxazol-6-yl)-benzenesulfonamide 1,2,5-Oxadiazole-3-carboximidamide, 4-amino-N'-(3-chloro-4-fluorophenyl)-N-hydroxy- INCB024360 4-Amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide IDO-IN-1 IDO5L |
| Description | IDO5L is a potent indoleamine 2,3-dioxygenase (IDO) inhibitor with an IC50 of 67 nM. |
|---|---|
| Related Catalog | |
| Target |
IDO:67 nM (IC50) IDO:19 nM (IC50, in HeLa cell) |
| In Vitro | IDO5L (Compound 5l) is a potent (HeLa IC50=19 nM) inhibitor of IDO[1]. IDO5L is one of the highest potent inhibitors of the IDO1 (IC50=19 nM, in HeLa cell assay)[2]. |
| In Vivo | Testing of IDO5L in mice demonstrates pharmacodynamic inhibition of IDO, as measured by decreased kynurenine levels (>50%) in plasma and dose dependent efficacy in mice bearing GM-CSF-secreting B16 melanoma tumors. Initial oral pharmacokinetic studies show that IDO5L is rapidly cleared (t1/2<0.5 h) and that oral administration will not be a suitable dosing method for in vivo studies. The measured plasma exposure (2.5 μM) of IDO5L during this period exceeded our calculated mouse protein binding adjusted B16 cellular IC50 (PBadjIC50=1.0 μM, murine cellular B16 IC50=46 nM). Notably, kynurenine levels increase back to baseline after 4 h as IDO5L exposure levels decreased below the mouse PBadjIC50 from 1.0 to 0.1 μM[1]. |
| Animal Admin | Mice[1] A single subcutaneous 100 mg/kg dose of IDO5L is administered to naive C57BL/6 mice bearing GM-CSF-secreting B16 tumors. Blood is harvested from individual mice over 8 h. Kynurenine and IDO5L concentrations are measured by LCMS. Reductions of kynurenine levels by 50-60% are observed between 2 and 4 h, with maximum inhibition seen at 2.5 h. Tumors are allowed to grow until day 7 when 14 days of subcutaneous dosing of IDO5L at 25, 50, and 75 mg/kg b.i.d. is initiated. Dose dependent inhibition of tumor growth is correlated with increasing exposures of IDO5L in plasma. |
| References |
| Density | 1.8±0.1 g/cm3 |
|---|---|
| Boiling Point | 504.7±60.0 °C at 760 mmHg |
| Molecular Formula | C9H7ClFN5O2 |
| Molecular Weight | 271.636 |
| Flash Point | 259.0±32.9 °C |
| Exact Mass | 271.027222 |
| PSA | 109.56000 |
| LogP | 4.30 |
| Vapour Pressure | 0.0±1.4 mmHg at 25°C |
| Index of Refraction | 1.715 |
| Storage condition | -20°C |