HDAC6-IN-13

Product NameHDAC6-IN-13
CAS2837128-41-1
MFC23H22N4O
MW370.45
EINECS
MOL File2837128-41-1.mol

Chemical Properties

Boiling point	562.289±50.00 °C(Press: 760.00 Torr)(predicted)
Density	1.213±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)
pka	12.536±0.23(predicted)
form	Solid
color	Light yellow to yellow

Usage And Synthesis

Uses

HDAC6-IN-13 (Compound 35m) is a potent, highly selective, orally active HDAC6 inhibitor with an IC50 of 0.019 μM. HDAC6-IN-13 also inhibits HDAC1, HDAC2 and HDAC3 with IC50s of 1.53, 2.06 and 1.03 μM, respectively. HDAC6-IN-13 shows significant BBB permeability and anti-inflammatory activity[1].

in vivo

HDAC6-IN-13 (Compound 35m) (20 mg/kg; p.o. and i.p.; once) displays a remarkable inhibition in LPS-induced inflammation in mice^[1].
HDAC6-IN-13 (20 mg/kg; p.o.; once) shows very high oral bioavailability (F% = 93.4%) and significant BBB permeability in mice^[1].

Animal Model:	Male C57BL/6 WT mice, LPS-induced endotoxic shock model^[1]
Dosage:	20 mg/kg
Administration:	PO and IP, immediately after the LPS injection
Result:	Significantly decreased the serum IL-1β levels in LPS-induced mice via both ip and po administration.

Animal Model:

Male CD-1 mice^[1]

Dosage:

5 mg/kg or 20 mg/kg

Administration:

IV (5 mg/kg) or PO (20 mg/kg) (Pharmacokinetic Study)

Result:

Pharmacokinetics Characterization of HDAC6-IN-13 (Compound 35m) with iv and Oral Administration^a^[1]

PK parameters	HDAC6-IN-13	HDAC6-IN-13
administered dose (mg/kg)	iv at 5 mg/kg	oral at 20 mg/kg
C_max (ng/mL)	4604 ± 551	5570 ± 551
t_1/2 (h)	7.95 ± 0.370	6.80 ± 0.145
AUC_0inf (ngh/mL)	2755 ± 395	10292 ± 1385
F%	n/a	93.4 ± 12.6

^aHDAC6-IN-13 was administrated via iv and po (n = 3). The blood sample was collected at different time points after dosing, and the plasma concentration of HDAC6-IN-13 was determined via LC-MS/MS. The area under the plasma concentration versus time curve (AUC) was calculated using the linear trapezoidal method. The pharmacokinetic parameters were obtained using the noncompartmental method. Data are shown as mean ± SD.

IC 50

HDAC6: 0.019 μM (IC₅₀); HDAC3: 1.03 μM (IC₅₀); HDAC1: 1.53 μM (IC₅₀); HDAC2: 2.06 μM (IC₅₀)

References

[1] Yue K, et al. First-in-Class Hydrazide-Based HDAC6 Selective Inhibitor with Potent Oral Anti-Inflammatory Activity by Attenuating NLRP3 Inflammasome Activation. J Med Chem. 2022 Sep 8. DOI:10.1021/acs.jmedchem.2c00853

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