NCGC-023
NCGC-023 is a LATS1/2 inhibitor. NCGC-023 selectively inhibits LATS1/2, an upstream regulator of Yap in the Hippo signaling pathway, increases the expression of active Yap protein, activates Yap-dependent signaling pathways, triggers non-Yap-dependent metallothionein-mediated heavy metal responses, and upregulates IL-33-related regenerative responses. NCGC-023 can be used in studies related to gastrointestinal acute radiation syndrome (GI-ARS).
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- CAS No.: 3024011-79-5
- Formule: C26H32FN3O3S
- Masse moléculaire:485.61
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Activité biologique
Description
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Lats1 |
Lats2 |
Yap |
IL-33 |
In Vitro
NCGC-023 potently inhibits purified LATS1 and LATS2 proteins in cell-free biochemical assays, with IC50 values of 14.1 nM and 14.7 nM, respectively[1].
NCGC-023 (1 hour) engages and inhibits LATS1 and LATS2 in HEK293 cells, with IC50 values of 367 nM and 57 nM, respectively[1].
NCGC-023 (4 hours) activates Yap-mediated gene expression in HepG2 human hepatocellular carcinoma cells[1].
NCGC-023 (3 μM; 48 hours) induces substantial nuclear localization of Yap protein in human jejunal enteroid line J2[1].
NCGC-023 (1-3 μM; 24 hours prior to irradiation) significantly improves clonogenicity and preserves viability of human jejunal enteroid lines J2 and J3 exposed to 4 or 6 Gy X-rays[1].
NCGC-023 (1-3 μM; 24 hours) does not induce aberrant growth or morphological changes in unirradiated human jejunal enteroid lines J2 and J3[1].
NCGC-023 (1-3 μM; 24 hours prior to irradiation) significantly improves clonogenicity of control mouse colonic organoids exposed to 6 Gy X-rays[1].
NCGC-023 (1-3 μM; 24 hours) does not promote growth of unirradiated Trp53 KO or Apc KO mouse colonic organoids, and decreases clonogenicity of Trp53 KO organoids at 3 μM[1].
NCGC-023 (1-3 μM; 24 hours prior to irradiation) decreases clonogenicity of Trp53 KO and Apc KO mouse colonic organoids exposed to 6 Gy X-rays[1].
NCGC-023 protects human enteroids from high-dose radiation-induced death[2].
NCGC-023 does not promote oncogenesis in pre-malignant murine enteroids[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Human jejunal enteroid line J2
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Concentration:3 μM
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Incubation Time:48 hours
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Result:Induced substantial nuclear localization of Yap protein.
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Cell Line:Unirradiated human jejunal enteroid lines J2 and J3
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Concentration:1-3 μM
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Incubation Time:24 hours
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Result:Did not result in significant growth or morphological changes compared to DMSO controls.
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Cell Line:Unirradiated Trp53 KO or Apc KO mouse colonic organoids
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Concentration:1-3 μM
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Incubation Time:24 hours
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Result:Did not promote growth.
Decreased clonogenicity at 3 μM in Trp53 KO organoids.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6N (8-12 weeks old, male and female, age- and sex-matched littermates, subjected to 13.5 Gy sub-total-body irradiation with ~20% lead shielding of head and forelimbs)[1]
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Dosage:50 mg/kg
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Administration:i.p.; two doses (24 hr and 2 hr prior to irradiation)
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Result:Increased the number of BrdU+ regenerating crypts and Olfm4+ intestinal stem cell-containing crypts 96 hours post-irradiation.
Reduced GI-ARS-associated mortality from 60% to 20% within 10 days post-irradiation.
Supported faster body weight recovery, with return to baseline by week two post-irradiation.
Improved long-term survival to 70% at 4 months post-irradiation (compared to 40% for vehicle controls).
Reduced radiation-induced aberrant mitoses in crypt cells at 24 and 72 hours post-irradiation.
Decreased γH2AX+ crypt cells (a marker of DNA damage) at 24 hours post-irradiation.
Reduced the number of mitotic crypt cells with unrepaired DNA damage (γH2AX+/pHH3+ double-positive cells) at 24 hours post-irradiation.
Increased the percentage of Fgfbp1+ crypt cells 24 hours post-irradiation.
Increased the number of p53+ crypt cells 48 hours post-irradiation.
Expanded the distribution of Clu+ revival stem cells from the crypt-villus junction to the crypt base 48 and 72 hours post-irradiation.
Increased total crypt count 72 hours post-irradiation.
Did not increase BrdU+ epithelial cells or fibrosis in the small intestine or colon at 4 months post-irradiation.
Did not exacerbate delayed injury in the small intestine, colon, kidneys, liver, or lungs at 4 months post-irradiation.
Chemical Information
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CAS No. 3024011-79-5
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Masse moléculaire 485.61
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Formule C26H32FN3O3S
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SMILES
C[C@H]1CN(C[C@H]([C@@]1(C2=CC=C(C=C2C)C3=C4C(F)=CNC4=NC=C3)O)C)C5CCS(=O)(CC5)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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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)
NCGC-023 Related Classifications
HY-187678 Related Classifications
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