INCB024360 is a potent IDO1 inhibitor (IC50 value of 10 nM) with desirable pharmaceutical properties, is poised to start clinical trials in cancer patients. In cellular assays, INCB024360 selectively inhibits human IDO1 with IC(50) values of approximately 10nM, demonstrating little activity against other related enzymes such as IDO2 or tryptophan 2,3-dioxygenase (TDO).
In vivo: In mice bearing GM-CSF-secreting B16 tumors, INCB024360 (75 mg/kg b.i.d) causes dose dependent inhibition of tumor growth. INCB024360 significantly suppresses tumor growth in immunocompetent, but not immunodeficient, mice.
In vitro: In HeLa cells, INCB024360 shows higher inhibitory activity on IDO1 with IC50 of 19 nM. In coculture systems of human allogeneic lymphocytes with dendritic cells or tumor cells, INCB024360, via IDO1 inhibition, reverses T-cell suppression mediated by IDO-expressing HeLa cells or DCs, and increases the proliferation and functional activity of CD4+ T cells, CD8+ T cells, and NK cells.
|Animal models||Mice bearing GM-CSF-secreting B16 tumors|
|Formulation||5% DMA, 47.5% propylene glycol|
|Dosages||75 mg/kg b.i.d|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO >13.6 mg/mL|
Structural insights into the binding mechanism of IDO1 with hydroxylamidine based inhibitor INCB14943.
Wu Y, et al. Biochem Biophys Res Commun. 2017 May 27;487(2):339-343. PMID: 28412361.
Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas.
Maliniemi P, et al. Oncoimmunology. 2017 Feb 10;6(3):e1273310. PMID: 28405495.
The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy.
Brochez L, et al. Eur J Cancer. 2017 May;76:167-182. PMID: 28324751.
|Related IDO Products|
1-Methyl-L-tryptophan is an inhibitor of indoleamine 2,3-dioxygenase (IDO).
LM10 is a selective tryptophan 2,3-dioxygenase (TDO) inhibitor (IC50 values are 0.62 and 2 μM for human and mouse TDO, respectively).
Palmatine chloride is an orally active and irreversible indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor.
Indoximod, also known as NLG8189 and D-1MT is an indoleamine 2,3-dioxygenase (IDO) pathway inhibitor with a Ki value of 19 μM.
IDO-IN-1 is a potent and selective indoleamine-2,3-dioxygenase (IDO) inhibitor with IC50 of 59 nM.
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