JAK/HDAC-IN-5
JAK/HDAC-IN-5 is an orally active dual JAK/HDAC inhibitor that inhibits JAK1 (IC50 = 8.8 nM), JAK2 (2.1 nM), JAK3 (24 nM), and TYK2 (13 nM), and inhibits HDAC1 (49 nM), HDAC2 (5.3 nM), HDAC3 (14 nM), and HDAC6 (3.1 nM). JAK/HDAC-IN-5 inhibits LPS-induced NO release and TNF-α-induced STAT phosphorylation. JAK/HDAC-IN-5 ameliorates Imiquimod (HY-B0180)-induced psoriasis-like skin inflammation.
For research use only. We do not sell to patients.
- CAS No.: 3121277-22-0
- Formula: C27H31N7O5S
- Molecular Weight:565.64
-
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]
-
Biological Activity
-
Chemical Information
- Protocols
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
JAK1 8.8 nM (IC50) |
JAK2 2.1 nM (IC50) |
JAK3 24 nM (IC50) |
Tyk2 13 nM (IC50) |
HDAC1 49 nM (IC50) |
HDAC2 5.3 nM (IC50) |
HDAC3 14 nM (IC50) |
HDAC6 3.1 nM (IC50) |
HDAC8 >1000 nM (IC50) |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| HaCaT | IC50 |
1.2 μM
|
Antiproliferative activity against TNF-α-stimulated human HaCaT keratinocytes assessed by CCK-8 viability assay after 48 hrs incubation.
Antiproliferative activity against TNF-α-stimulated human HaCaT keratinocytes assessed by CCK-8 viability assay after 48 hrs incubation.
|
Design-Synthesis-and-Biological-Evaluation-of |
| HEK-293T | IC50 |
69 μM
|
Antiproliferative activity against human HEK293T cells.
Antiproliferative activity against human HEK293T cells.
|
Design-Synthesis-and-Biological-Evaluation-of |
In Vitro
JAK/HDAC-IN-5 (0.1-0.9 µM; 24 h) increases histone H3/H4 acetylation in TNF-α-stimulated HaCaT cells at 0.9 µM, and inhibits p-STAT3 at 0.1 and 0.9 µM, with a stronger inhibitory effect on p-STAT3 at 0.9 µM[1].
JAK/HDAC-IN-5 is a potent HDAC6 inhibitor in cell-free HDAC isoform assays (IC50 = 3.1 nM), with selectivity for HDAC8[1].
JAK/HDAC-IN-5 shows moderate Caco-2 permeability, with Papp (AB) = 2.95 µcm/s and ER = 3.33[1].
JAK/HDAC-IN-5 shows good metabolic stability in ICR mouse liver microsomes, T1/2 = 15.7 min, clearance = 349.3 mL/min/kg[1].
JAK/HDAC-IN-5 shows moderate antiproliferative activity in HEK293T cells, with IC50 = 69 µM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:HaCaT
-
Concentration:0.19-100 µM
-
Incubation Time:48 h
-
Result:Inhibited TNF-α-stimulated HaCaT proliferation with IC50 = 1.2 µM.
-
Cell Line:HaCaT
-
Concentration:0.1 and 0.9 µM
-
Incubation Time:24 h
-
Result:At 0.9 µM, acetyl-H3 and acetyl-H4 levels were increased; at 0.1 µM, acetyl-H3 was not increased but acetyl-H4 was increased.
Total H3/H4 levels remained largely unchanged. p-STAT3 was reduced at both 0.1 and 0.9 µM, with a greater reduction at 0.9 µM.
In Vivo
JAK/HDAC-IN-5 (20 mg/kg; p.o.; once daily; 7 days) retains considerable efficacy, reducing skin lesions and epidermal hyperplasia in IMQ-induced BALB/c mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:BALB/c (female, 6 weeks old, 18-20 g)[1]
-
Dosage:0.5% cream
-
Administration:topical
-
Result:Exposed mice showed nearly normal dorsal skin without apparent erythema or scales, with skin color comparable to normal mice.
Spleen index was lowest among all application groups.
HE staining showed markedly reduced stratum spinosum thickness, close to normal histology, with the most potent effect among application groups, superior to compounds 1, 2, and their combination.
-
Animal Model:BALB/c (female, 6 weeks old, 18-20 g)[1]
-
Dosage:20 mg/kg
-
Administration:p.o.; once daily; 7 days
-
Result:Oral administration alleviated IMQ-triggered cutaneous erythema and scaling symptoms.
IMQ-induced splenomegaly was effectively relieved.
HE staining showed reduced epidermal stratum spinosum thickness, superior to compounds 1, 2, and their combination, with the most potent efficacy in alleviating epidermal hyperplasia among all experimental groups.
Oral efficacy was inferior to that achieved by topical administration.
Chemical Information
-
CAS No. 3121277-22-0
-
Molecular Weight 565.64
-
Formula C27H31N7O5S
-
SMILES
O=C(C(N1)=CC2=C1C=CC(NC3=NC=CC(C4=CC=C(NS(=O)(C)=O)C=C4)=N3)=C2)NCCCCCCC(NO)=O
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
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)
JAK/HDAC-IN-5 Related Classifications
HY-191434 Related Classifications
Powered by Bioz