Art. -Nr.: HY-18542

KT195

KT195 is a serine hydrolase inhibitor that targets ABHD6 (IC₅₀ = 10 nM) and ABHD2, with no significant activity against DAGLβ. KT195 inhibits endoplasmic reticulum calcium release and mitochondrial calcium uptake by targeting ABHD2, thereby blocking A23187 (HY-N6687) and H₂O₂-induced necrotic cell death and apoptosis. By inhibiting ABHD6 activity, KT195 significantly induces 2-AG accumulation in Neuro2A cells and reduces IL-1β secretion in lipopolysaccharide-treated macrophages. KT195 has been used as a negative control probe for DAGLβ and can be applied in studies of ABHD6 and ABHD2 in calcium signaling, lipid metabolism, neuronal function, and inflammatory.

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CAS. Nr.: 1402612-58-1
Formel: C₂₇H₂₆N₄O₂
Molecular Weight:438.52

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Please store the product under the recommended conditions in the Certificate of Analysis.

KT195 Chemical Structure

CAS. Nr.: 1402612-58-1

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Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
- In Vivo
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Beschreibung

IC₅₀ & Target^[1]^[2]^[3]

ABHD6

10 nM (IC₅₀)

ABHD2

In Vitro

KT195 (0.2-2 μM; pretreated for 30 min) significantly inhibits 50 μMH₂O₂-induced apoptosis in MLF cells, partially inhibits 1 mM H₂O₂-induced [³H]arachidonic acid release and LDH release, and inhibits MPTP formation; in IMLF α⁻/⁻ cells, it concentration-dependently inhibits A23187-induced [³H]arachidonic acid release and LDH release (IC₅₀ ≈ 0.7 μM); but it shows no inhibitory effect on 250 nM Staurosporine (HY-15141)-induced apoptosis^[1]^[2].
KT195-alkyne (0.2-10 μM; 1 h) labels ABHD2 and ABHD6 in a concentration-dependent manner in the IMLF cell membrane proteome^[1].
KT195-alkyne (30 min) inhibits A23187 (HY-N6687)-induced necrotic cell death in IMLF cells, with an IC₅₀ of approximately 1.5 μM, comparable to unmodified KT195 (IC₅₀ 0.7 μM)^[1].
KT195 (10 μM) competitively blocks the binding of KT195-alkyne to ABHD2 in IMLF cells, indicating that ABHD2 is a target of KT195^[1].
KT195 (2 μM; pretreated for 30 min + co-incubated with A23187 for 30 min) still inhibits A23187-induced [³H]arachidonic acid release and LDH release in ABHD6-knockdown IMLF α⁻/⁻ cells, indicating that its anti-necrotic effect is independent of ABHD6^[2].
KT195 (0.025-2 μM) completely blocks HT-01 probe binding to ABHD6 in IMLF α⁻/⁻ cells and concentration-dependently inhibits HT-01 probe binding to ABHD6 in the IMLF α⁻/⁻ membrane proteome, with an IC₅₀ of approximately 25 nM^[2].
KT195 (pretreated for 30 min + co-incubated with A23187 for 30 min) completely blocks mitochondrial calcium uptake in IMLF α⁻/⁻ cells, but only partially reduces cytosolic calcium elevation^[2].
KT195 (2 μM; pretreated for 30 min + co-incubated with 20 μMThapsigargin for 60 min) shows no significant inhibitory effect on Thapsigargin-induced [³H]arachidonic acid release and LDH release in IMLF α⁻/⁻ cells^[2].
KT195 (2 μMor 10 μM; pretreated for 30 min then washed out) fails to inhibit [³H]arachidonic acid release and LDH release in IMLF α⁻/⁻ cells when stimulated with A23187 30 min after washout, indicating that its inhibitory effect is reversible or requires continuous target occupancy^[2].
KT195 (0.0032-10 μM; 4 h) shows potent inhibitory activity against ABHD6 in recombinant proteomes, tissue proteomes, Neuro2A cells, and PC3 cells (ex vivo IC₅₀ = 10 nM; in situ IC₅₀ ≈ 1 nM), but shows no activity against DAGLβ or other detected serine hydrolases (DAGLβ IC₅₀ > 10 μM); it does not affect SAG, 2-AG, or arachidonic acid levels in Neuro2A and PC3 cells, but induces significant accumulation of 2-AG^[3].
KT195 (2 μM; pretreated for 30 min) fully binds and inhibits ABHD6 in rat primary cortical neurons, but shows no significant inhibitory effect on NMDA (100 μM, 15 min)-induced excitotoxic cell death and mitochondrial calcium elevation^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Apoptosis Analysis^[1]

Cell Line:

MLF cells
Concentration:

2 μM
Incubation Time:

30 min pretreatment + 6 h stimulation (with 50 μMH₂O₂)
Result:

Significantly inhibited apoptosis (decreased Annexin V-positive cells) induced by 50 μMH₂O₂, but showed no inhibition against 250 nM staurosporine-induced apoptosis.

Apoptosis Analysis^[2]

Cell Line:

IMLF α⁻/⁻ cells
Concentration:

0.2, 1 and 2 μM
Incubation Time:

30 min pretreatment + 30 min stimulation (with A23187)
Result:

Significantly inhibited [³H]arachidonic acid release and LDH release (necrotic cell death) induced by A23187 (1 μg/ml), with an IC₅₀ of ~0.7 μM(determined from concentration-response curve).

Cell Cytotoxicity Assay^[2]

Cell Line:

ABHD6-knockdown IMLF α⁻/⁻ cells and MLF α⁺/⁺ /α⁻/⁻ cells
Concentration:

2 μM
Incubation Time:

30 min pretreatment + 30 min stimulation (with A23187) for ABHD6-knockdown cells; 30 min pretreatment + 18 h stimulation (with H₂O₂) for MLF cells
Result:

Still inhibited A23187-induced [³H]arachidonic acid release and LDH release in ABHD6-knockdown IMLF cells; partially inhibited H₂O₂-induced [³H]arachidonic acid release (~36–44% in MLF α⁺/⁺ ; ~55% in MLF α⁻/⁻) and LDH release (~45–50%) in MLF cells, and inhibited MPTP formation (calcein fluorescence quenching). These results indicate that its anti-necrotic effect is independent of ABHD6.

Cell Cytotoxicity Assay^[2]

Cell Line:

IMLF α⁻/⁻ cells
Concentration:

2 μM or 10 μM
Incubation Time:

30 min pretreatment + 30 min stimulation (with A23187)
Result:

Failed to inhibit [³H]arachidonic acid release or LDH release induced by A23187 (1 μg/ml) when cells were washed to remove the inhibitor after pretreatment, indicating that its inhibitory effect requires continuous target occupancy.

Cell Cytotoxicity Assay^[2]

Cell Line:

IMLF α⁻/⁻ cells
Concentration:

2 μM
Incubation Time:

30 min pretreatment + 60 min stimulation (with Thapsigargin)
Result:

Showed no significant inhibition of [³H]arachidonic acid release or LDH release induced by Thapsigargin (20 μM).

Cell Cytotoxicity Assay^[4]

Cell Line:

Rat primary cortical neurons
Concentration:

2 μM
Incubation Time:

30 min pretreatment + 15 min NMDA stimulation + 24 h recovery
Result:

Showed no significant inhibition of NMDA (100 μM)-induced excitotoxic cell death (LDH release).

In Vivo

KT195 (0.1-10 mg/kg; i.p.; single dose; 4 h) does not inhibit DAGLβ, but inhibits ABHD6 and off-targets (CES3/CES2G/PLA2G15) in mouse peritoneal macrophages; at 5 mg/kg, it shows no effects on the aforementioned lipid mediators or TNF-α release^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Female C57BL/6 mice (6-8 weeks old) were intraperitoneally injected with 4% (w/v) thioglycollate medium (2.5 mL per mouse) to induce peritoneal macrophage recruitment, and compound treatment was administered 4 days later^[3].
Dosage:

0.1, 0.5, 1, 5, 10 mg/kg (dose-response study); 5 mg/kg (time-course, metabolomics, and cytokine studies); 2 or 5 mg/kg (ABPP-MudPIT study)
Administration:

Intraperitoneal injection (i.p.); single dose
Result:

Showed no inhibitory activity against DAGLβ at any dose tested (0.1-10 mg/kg) as measured by gel-based competitive ABPP with the HT-01 probe.
Showed dose-dependent inhibition of ABHD6 at ≥0.5 mg/kg, with complete inhibition observed at 5 mg/kg.
Showed no inhibition of DAGLβ across the entire time course (1-16 h) at 5 mg/kg.
ABPP-MudPIT analysis at 5 mg/kg for 4 h confirmed inhibition of ABHD6 but not DAGLβ; also inhibited off-targets CES3, CES2G, and PLA2G15 (activity reduced by ~50-80%).
At 5 mg/kg for 4 h, showed no significant effects on 2-AG, SAG (C18:0/C20:4 DAG), arachidonic acid, PGE₂, or PGD₂ levels in peritoneal macrophages.
At 5 mg/kg for 2 h, macrophages were isolated and stimulated with LPS (5 μg/mL, 90 min); showed no significant inhibition of TNF-α release.

Chemical Information

CAS. Nr. 1402612-58-1
Molecular Weight 438.52
Formel C₂₇H₂₆N₄O₂
SMILES

O=C(N1CCCCC1C2=CC=CC=C2)N3N=NC(C4=CC=C(C5=CC=C(OC)C=C5)C=C4)=C3
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Reinheit & Dokumentation

Handling Instructions (2659 KB)

Verweise

[1]. Yun B, et al. Regulation of calcium release from the endoplasmic reticulum by the serine hydrolase ABHD2. Biochem Biophys Res Commun. 2017 Sep 2;490(4):1226-1231. [Content Brief]

[2]. Yun B, et al. Serine hydrolase inhibitors block necrotic cell death by preventing calcium overload of the mitochondria and permeability transition pore formation. J Biol Chem. 2014 Jan 17;289(3):1491-504. [Content Brief]

[3]. Hsu KL, et al. DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses. Nat Chem Biol. 2012 Dec;8(12):999-1007. [Content Brief]

[4]. Manterola A, et al. Re-examining the potential of targeting ABHD6 in multiple sclerosis: Efficacy of systemic and peripherally restricted inhibitors in experimental autoimmune encephalomyelitis. Neuropharmacology. 2018 Oct;141:181-191. [Content Brief]

Calculators

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Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

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KT195

17-ODYA

1,4-DPCA

JW480

17-ODYA (Standard)

JW480 (Standard)

12(S)-Hydroxy-16-heptadecynoic acid

Palmitoylisopropylamide

Biologische Aktivität

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KT195

17-ODYA

1,4-DPCA

JW480

17-ODYA (Standard)

JW480 (Standard)

12(S)​-​Hydroxy-​16-​heptadecynoic acid

Palmitoylisopropylamide

Biologische Aktivität

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KT195 Related Classifications

HY-18542 Related Classifications

12(S)-Hydroxy-16-heptadecynoic acid