INCB024360 analogue(IDO-IN-1)

INCB14943, also known as INCB024360-analog, IDO5L and IDO-IN-2 with CAS#914471-09-3, is a potent and orally available hydroxyamidine and inhibitor of indoleamine 2, 3-dioxygenase (IDO1) with potential immunomodulating and antineoplastic activities. INCB024360-analog is a potent (HeLa IC50=19 nM) competitive inhibitor of IDO. Testing of INCB024360-analog in mice demonstrated pharmacodynamic inhibition of IDO, as measured by decreased kynurenine levels (>50%) in plasma and dose dependent efficacy.

Product information

CAS Number: 914471-09-3

Molecular Weight: 271.64

Formula: C9H7ClFN5O2

Synonym:

INCB14943

Epacadostat-analog

IDO-IN-2

IDO5L

INCB-14943

INCB 14943

INCB024360-analog

INCB24360-analog

Chemical Name:  4-amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide

Smiles: NC1=NON=C1C(NC1=CC(Cl)=C(F)C=C1)=NO

InChiKey: HGXSLPIXNPASGZ-UHFFFAOYSA-N

InChi: InChI=1S/C9H7ClFN5O2/c10-5-3-4(1-2-6(5)11)13-9(14-17)7-8(12)16-18-15-7/h1-3,17H,(H2,12,16)(H,13,14)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

IDO5L (Compound 5l) is a potent (HeLa IC50=19 nM) inhibitor of IDO. IDO5L is one of the highest potent inhibitors of the IDO1 (IC50=19 nM, in HeLa cell assay).

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.

References:

1. Devaraja K. Current Prospects of Molecular Therapeutics in Head and Neck Squamous Cell Carcinoma. Pharmaceut Med. 2019 Aug;33(4):269-289. doi: 10.1007/s40290-019-00288-x. PubMed PMID: 31933185.
2. Chu CE, Porten SP, Grossfeld GD, Meng MV. Role of Indoleamine-2,3-Dioxygenase Inhibitors in Salvage Therapy for Non-Muscle Invasive Bladder Cancer. Urol Clin North Am. 2020 Feb;47(1):111-118. doi: 10.1016/j.ucl.2019.09.013. Review. PubMed PMID: 31757294.
3. Rohrig UF, Reynaud A, Majjigapu SR, Vogel P, Pojer F, Zoete V. Inhibition Mechanisms of Indoleamine 2,3-Dioxygenase 1 (IDO1). J Med Chem. 2019 Oct 10;62(19):8784-8795. doi: 10.1021/acs.jmedchem.9b00942. Epub 2019 Sep 26. PubMed PMID: 31525930.

Products are for research use only. Not for human use.