HDAC1-IN-16
HDAC1-IN-16 is a potent and selective HDAC1 inhibitor and antimalarial agent, with IC50 values of 2.2 nM and 0.223-0.248 nM against hHDAC1 and PfHDAC1, respectively. HDAC1-IN-16 induces histone hyperacetylation by inhibiting PfHDAC1, interferes with gene expression, thereby inhibits merozoite growth and reinvasion, and exhibits killing effects in the erythrocytic, hepatic, and gametocyte stages. HDAC1-IN-16 can be used for research on malaria.
For research use only. We do not sell to patients.
- CAS No.: 2482998-34-3
- Formula: C22H23N7O2
- Molecular Weight:417.47
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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- Purity & Documentation
- References
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Biological Activity
Description
IC50 & Target
[1]|
hHDAC1 2.2 nM (IC50) |
PfHDAC1 0.223-0.24 nM (IC50) |
hHDAC2 5.1 nM (IC50) |
hHDAC3 5.2 nM (IC50) |
hHDAC6 85.5 nM (IC50) |
hHDAC8 29.9 nM (IC50) |
hSIRT2 > 10000 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HepG2 | IC50 |
1.02 μM
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Cytotoxicity against human HepG2 cells assessed as viability reduction after 72 hrs incubation by CCK-8 assay.
Cytotoxicity against human HepG2 cells assessed as viability reduction after 72 hrs incubation by CCK-8 assay.
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acs.jmedchem.1c01993 |
| HEK-293T | IC50 |
1.21 μM
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Cytotoxicity against human 293T cells assessed as viability reduction after 72 hrs incubation by CCK-8 assay.
Cytotoxicity against human 293T cells assessed as viability reduction after 72 hrs incubation by CCK-8 assay.
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acs.jmedchem.1c01993 |
In Vitro
HDAC1-IN-16 (48 h) inhibits gametocyte survival in P. falciparum NF54 strain (stage II and stage IV gametocytes), with IC50 values of 15.83 nM and 12.42 nM, respectively[1].
HDAC1-IN-16 (10-100 nM; 3-24 h) exhibits time- and dose-dependent killing effects in asynchronous P. falciparum 3D7 strains[1].
HDAC1-IN-16 (40 nM; 12 h) irreversibly inhibits erythrocyte reinvasion and schizont growth in highly synchronized P. falciparum 3D7 strains (ring, trophozoite, and schizont stages)[1].
HDAC1-IN-16 (700 nM; 6 h) potently inhibits the growth of Artemisinin-resistant strains in the Artemisinin (HY-B0094)-resistant mutant strains 6218 and 6320[1].
HDAC1-IN-16 (5-20 nM; 4 h) dose-dependently inhibits PfHDAC in the P. falciparum 3D7 strain, thereby causing histone H3 hyperacetylation[1].
HDAC1-IN-16 (72 h) exhibits potent activity against multidrug-resistant P. falciparum GB4, C2A, and CP286, with IC50 values of 3.06, 2.18, and 5.85 nM, respectively[1].
HDAC1-IN-16 (4 h) is selective for human HDAC enzymes, with IC50 values of 2.2, 5.1, 5.2, 85.5, 29.9, and > 10000 nM for hHDAC1, hHDAC2, hHDAC3, hHDAC6, hHDAC8, and SIRT2, respectively[1].
HDAC1-IN-16 (50-800 nM; 120 min) has direct inhibitory activity against the catalytic activity of recombinant PfHDAC1 enzyme, with an IC50 of 0.223-0.248 nM.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human HepG2 and 293T cells
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Concentration:20 μM (doubly diluted from highest concentration)
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Incubation Time:72 h
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Result:Exhibited attenuated cytotoxicity (IC50 around 1 μM) and improved selectivity index compared to the parent drug Quisinostat.
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Cell Line:asynchronous P. falciparum 3D7 strain
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Concentration:5 nM, 20 nM
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Incubation Time:4 h
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Result:Induced hyperacetylation of parasite histone H3, verifying the inhibition of PfHDAC functions inside the cells.
Parmacokinetics
| Species | Dose | Route | Cmax | Tmax | AUClast | AUCinf | T1/2 | CLz/F | Vz/F |
|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 5 mg/kg | i.p. | 539 ng/mL | 0.25 h | 638 ng·h/mL | 640 ng·h/mL | 0.91 h | 7.81 L/h/kg | 10.20 L/kg |
In Vivo
HDAC1-IN-16 (30 mg/kg; i.v.; single administration; 4-day observation) effectively kills liver-stage malaria parasites and blocks their transition to the blood stage in a BALB/c mouse liver-stage infection model intravenously inoculated with luciferase-expressing P. berghei sporozoites[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c (female, 6-8 weeks)[1]
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Dosage:30 mg/kg, 60 mg/kg, and 90 mg/kg
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Administration:i.p.; once daily for 5 successive days; observation up to 60 days
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Result:Demonstrated excellent therapeutic efficacy and safety compared to the lead compound Quisinostat.
Completely cured the infected mice at 90 mg/kg without any recrudescence or animal death.
No overt toxicity or body weight loss was observed.
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Animal Model:BALB/c (female, 6-8 weeks)[1]
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Dosage:30 mg/kg
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Administration:i.v.; single dose; 1, 2, 3, 4 days
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Result:Effectively delayed the progression of liver-stage infection and prevented the liver-stage to blood-stage transition.
Had better therapeutic effects and safety than Quisinostat in the liver stage.
Chemical Information
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CAS No. 2482998-34-3
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Molecular Weight 417.47
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Formula C22H23N7O2
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SMILES
N#CC=1C=CC2=C(C1)N(C=C2CN3CC4(CN(C5=NC=C(C=N5)C(=O)NO)CC4)C3)C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
HDAC1-IN-16 Related Classifications
HY-187929 Related Classifications
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