IHCH-3185
IHCH-3185 is an orally active class I HDAC inhibitor (HDAC1 IC50 =102.9 nM) and A2AR antagonist (A2AR Ki =7.6 nM). IHCH-3185 reverses immune gene silencing by inducing histone acetylation and blocks the adenosine signaling pathway to relieve T-cell suppression. IHCH-3185 exhibits antiproliferative activity, induces cell cycle arrest, and significantly improves the tumor microenvironment. IHCH-3185 reduces the proportion of regulatory T cells, increases the CD8+/Treg ratio, and upregulates the expression of key factors such as H2-K1, Cxcl9 and Cxcl10. IHCH-3185 shows significant antitumor potential in CT26 and MC38 mouse tumor models and is suitable for related cancer research.
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- Formule: C24H21N7O3
- Masse moléculaire:455.47
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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HDAC1 102.9 nM (IC50) |
A2AR 7.6 nM (Ki) |
IHCH-3185 (compound 13t) inhibits recombinant human HDAC1 (IC50=102.9 nM, 15 min), exerts moderate inhibitory effects on HDAC2 and HDAC3, and shows no inhibitory activity against HDAC4 or HDAC6 even at concentrations up to 10 μM[1].
IHCH-3185 inhibits the human A2AR receptor-mediated cAMP signaling pathway in HEK293-A2 AR cells, with an IC50 of 88 nM[1].
IHCH-3185 exhibits broad-spectrum antiproliferative activity in a variety of human and mouse tumor cell lines, with a GI50 ranging from 0.06 μM (DoHH2) to 1.8 μM (MC38, SK-BR-3)[1].
IHCH-3185 (0.3-3.0 μM; 48 h) induces G0/G1 phase arrest in a concentration-dependent manner in murine colon cancer cell lines CT26 and HCT-116 following treatment at concentrations of 0.3, 1.0 and 3.0 μM for 48 h[1].
IHCH-3185 (1.5 nM; 72 h) reverses the inhibitory effect of NECA on IFN-γ secretion in activated mouse splenocytes, with an incubation time of 72 h[1].
IHCH-3185 (0.3-3.0 μM; 24 h) induces concentration-dependent increases in the levels of acetylated histone H3 and H4 in CT26 and MC38 mouse colon cancer cells following treatment at 0.3, 1.0 and 3.0 μM for 24 h[1].
IHCH-3185 (1-10 μM; 24 h) upregulates the mRNA expression of H2-K1, Cxcl9 and Cxcl10 in MC38 mouse colon cancer cells in a concentration-dependent manner after 24 h of treatment at 1, 3 and 10 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:CT26, MC38, GP-2d, SW620, HCT-116, T-47D, SK-BR-3, NCI-H1975, PC-9, SU-DHL-4, DoHH2
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Concentration:0.00005-10 μM
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Incubation Time:72 h
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Result:Exhibited broad-spectrum antiproliferative activity with GI50 values of 0.38 μM (CT26), 1.8 μM (MC38), 0.6 μM (GP-2d), 0.6 μM (SW620), 0.2 μM (HCT-116), 0.8 μM (T-47D), 1.8 μM (SK-BR-3), 0.5 μM (NCI-H1975), 0.4 μM (PC-9), 0.5 μM (SU-DHL-4), and 0.06 μM (DoHH2).
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Cell Line:CT26, HCT-116 mouse colon cancer cell lines
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Concentration:0.3, 1.0, 3.0 μM
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Incubation Time:48 h
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Result:Induced a concentration-dependent G0/G1 phase arrest in both CT26 and HCT-116 cells, with significant increases in G0/G1 population and corresponding decreases in S phase population at all tested concentrations.
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Cell Line:CT26, MC38 mouse colon cancer cells
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Concentration:0.3, 1.0, 3.0 μM
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Incubation Time:24 h
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Result:Induced a concentration-dependent increase in acetylated H3 and H4 levels in both CT26 and MC38 cells, confirming functional HDAC inhibition.
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Cell Line:MC38 mouse colon cancer cells
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Concentration:1-10 μM
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Incubation Time:24 h
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Result:Significantly upregulated mRNA expression of H2-K1 (MHC-I), Cxcl9, and Cxcl10 in a concentration-dependent manner, with fold changes relative to vehicle control of ~2.5 (1 μM), ~3 (3 μM), and ~2.8 (10 μM) for H2-K1; ~2 (1 μM), ~4 (3 μM), and ~2.8 (10 μM) for Cxcl9; and ~2 (1 μM), ~4 (3 μM), and ~2.8 (10 μM) for Cxcl10.
| Species | Dose | Route | T1/2β | Tmax | Cmax | AUC0-t | AUC0-∞ | MRT | F | CL | Vdss |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 5 mg/kg | i.v. | 1.03 h | / | 6279 ng/mL | 5474 ng·h/mL | 5511 ng·h/mL | 0.966 h | / | 15.2 mL/min/kg | 0.881 L/kg |
| Mice[1] | 20 mg/kg | p.o. | 4.29 h | 0.667 h | 6911 ng/mL | 18605 ng·h/mL | 18808 ng·h/mL | 3.36 h | 85 % | / | / |
| Mice[1] | 100 mg/kg | p.o. | 6.33 h | 0.833 h | 38617 ng/mL | 134817 ng·h/mL | 139094 ng·h/mL | 4.48 h | 126 % | / | / |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male); BALB/c[1]
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Dosage:60-120 mg/kg (MC38 model); 90-120 mg/kg (CT26 model); 20 mg/kg (PK); 100 mg/kg (PK); 5 mg/kg (PK, IV)
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Administration:p.o.; qd; 14 days (antitumor efficacy); p.o. (PK, 20 mg/kg, 100 mg/kg); i.v. (PK, 5 mg/kg)
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Result:Achieved TGI of 47.1% (P < 0.05) at 60 mg/kg, 62.2% (P < 0.01) at 90 mg/kg, and 71.1% (P < 0.001) at 120 mg/kg in MC38 syngeneic model.
Achieved TGI of 50.9% (P < 0.01) at 90 mg/kg and 68.5% (P < 0.001) at 120 mg/kg in CT26 syngeneic model.
Showed high oral bioavailability of 85% at 20 mg/kg and 126% at 100 mg/kg in male C57BL/6 mice.
Reduced intratumoral regulatory T-cell populations and increased the CD8+ T-cell/Treg ratio in both CT26 and MC38 models.
Induced histone H3 acetylation in CT26 and MC38 tumor tissues.
Caused no significant body weight loss at all tested doses.
Chemical Information
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Masse moléculaire 455.47
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Formule C24H21N7O3
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SMILES
NC1=NC(OCCC2=CC=C(C=C2)C(NC3=CC=CC=C3N)=O)=CC4=NC(C5=CC=CO5)=NN41
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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