Lpi-1
Lpi-1 is an ATP-competitive LATS1/2 inhibitor with IC50 values of 4.4 nM and 1.3 nM, respectively. Lpi-1 blocks LATS-mediated YAP1 phosphorylation. Lpi-1 reversibly inhibits LATS1/2 in cells and in vivo, activating the YAP/TAZ signaling pathway. Lpi-1 can be used for research on acute liver injury and colitis.
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- CAS No.: 2251130-98-8
- Formule: C19H13ClFN3O2
- Masse moléculaire:369.78
-
Stockage:
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]
-
Activité biologique
-
Chemical Information
- Protocole
- Pureté et documentation
- Références
-
Help & FAQs
Voir tous les produits spécifiques à Isoform YAP
More
Activité biologique
Description
IC50 & Target
[1]|
Lats1 4.4 nM (IC50) |
Lats2 1.3 nM (IC50) |
Lats1 243.3 nM (Kd) |
Lats2 111.6 nM (Kd) |
YAP1 |
TAZ |
In Vitro
LPi-1 (30 min) binds directly to LATS1 and LATS2 with Kd values of 243.3 nM and 111.6 nM, respectively[1].
LPi-1 (100 μM) directly engages LATS1/2 and increases their thermal stability by 8.5°C and 9.5°C[1].
LPi-1 (0.1-10 μM; 1-8 h) reversibly inhibits LATS1/2, reduces YAP1/TAZ phosphorylation, and promotes nuclear YAP1/TAZ localisation and target gene expression in HepG2 cells; this effect is dose-dependent across multiple cell lines[1].
LPi-1 (10 days) promotes YAP-dependent proliferation and SOX9+/HNF4α+ biliary/progenitor transdifferentiation in primary mouse hepatocyte-derived CLiPs[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:HepG2 cells
-
Concentration:0.1 μM; 0.3 μM; 1 μM; 3 μM; 10 μM
-
Incubation Time:1 h; 2 h; 4 h; 5 h; 6 h; 8 h
-
Result:Reduced the phosphorylation levels of YAP1/TAZ.
-
Cell Line:HepG2 cells
-
Concentration:1 μM; 3 μM
-
Incubation Time:1 h; 2 h; 4 h; 5 h; 6 h; 8 h
-
Result:Promoted the nuclear localization of YAP1/TAZ in HepG2 cells.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | AUC0-inf | CL | MRT0-t | MRT0-inf |
|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 5 mg/kg | i.p. | 1.27 h | 0.0830 h | 1160 ng/mL | 1190 ng·h/mL | 1200 ng·h/mL | 69.4 mL/min/kg | 0.848 h | 0.971 h |
In Vivo
Chronic LPi-1 (3 mg/kg; i.p.; once daily; 2 months) increases liver progenitor/proliferation markers and liver/body weight ratio in healthy mice, and these effects reverse after LPi-1 withdrawal[1].
LPi-1 (3 mg/kg; i.p.; once daily; 4 weeks) increases liver progenitor/proliferation markers and liver/body weight ratio in postnatal mice[1].
LPi-1 (3 mg/kg; i.p.; at surgery and twice daily; 7 days) promotes liver regeneration after partial hepatectomy by enhancing hepatocyte proliferation and YAP/TAZ activation[1].
LPi-1 (3 mg/kg; i.p.; twice daily; beginning 1.5 h after APAP) ameliorates APAP-induced acute liver injury and improves survival in mice[1].
LPi-1 (3 mg/kg; i.p.; twice daily) protects against DSS-induced colitis and preserves colonocyte proliferation in mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:C57BL/6 (wild-type)[1]
-
Dosage:3 mg/kg; 0.3, 1, 3, 10, and 30 mg/kg
-
Administration:i.p.; single injection; dose-response
-
Result:Inhibition of YAP1/TAZ phosphorylation in liver reached a maximum at 2 h after i.p. injection of LPi-1 (3 mg/kg).
This inhibition in liver tissues was dose-dependent across 0.3, 1, 3, 10, and 30 mg/kg LPi-1.
-
Animal Model:C57BL/6 (male, 6-8 weeks old, 20-25 g)[1]
-
Dosage:3 mg/kg (2 months); 3 mg/kg (2 months then withdrawal 20 days)
-
Administration:i.p.; once daily; 2 months; 20 days withdrawal
-
Result:Wild-type mice receiving LPi-1 daily for 2 months exhibited a modest increase in the percentage of CK19-positive and Ki67-positive cells, as well as in the liver/body weight ratio, which subsequently returned to baseline levels 20 days after discontinuation of LPi-1.
-
Animal Model:C57BL/6 (male, 10 days old, 8-10 g)[1]
-
Dosage:3 mg/kg
-
Administration:i.p.; once daily; 4 weeks
-
Result:LPi-1 resulted in a moderate increase in the percentage of CK19-positive and Ki67-positive cells, as well as in the liver/body weight ratio, compared with vehicle controls.
-
Animal Model:C57BL/6 (male, 8-10 weeks old, 25-30 g)[1]
-
Dosage:3 mg/kg
-
Administration:i.p.; at surgery and twice daily; 7 days
-
Result:Significantly enhanced liver regeneration, as evidenced by a higher percentage of Ki67- and BrdU-positive cells in the liver and a more rapid increase in the liver/body weight ratio compared to controls between postoperative days 1 and 7.
Mice receiving LPi-1 exhibited decreased Yap1 and TAZ phosphorylation and increased expression of Ccn2/Ctgf and Ccn1/Cyr61 between postoperative days 2 and 6.
-
Animal Model:C57BL/6 (male, 6-8 weeks old, 20-25 g)[1]
-
Dosage:3 mg/kg
-
Administration:i.p.; twice daily; beginning 1.5 h after APAP
-
Result:In the lethal APAP model, LPi-1 increased survival from 10% to 70%.
APAP-fed mice receiving LPi-1 exhibited reduced centrilobular necrotic lesions and TUNEL+ cells at 6 h and prevented sustained expansion of necrosis at 12, 24, and 48 h.
LPi-1 lowered serum ALT and AST levels at specific hours following APAP feeding compared to controls.
-
Animal Model:C57BL/6 (male, 8-10 weeks old, 25-30 g)[1]
-
Dosage:3 mg/kg
-
Administration:i.p.; twice daily
-
Result:Mice receiving LPi-1 showed less weight loss, reduced colitis symptoms including diarrhea and rectal bleeding, more intact intestinal structure, and a higher percentage of Ki67-positive proliferating cells in colon crypts compared with vehicle controls.
Chemical Information
-
CAS No. 2251130-98-8
-
Masse moléculaire 369.78
-
Formule C19H13ClFN3O2
-
SMILES
O=C(C1=COC(C2=CNC3=C2C=CC=N3)=C1)NCC4=C(Cl)C=CC=C4F
-
Livraison
Room temperature in continental US; may vary elsewhere.
-
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)
Lpi-1 Related Classifications
HY-189122 Related Classifications
Powered by Bioz