HM-279
HM-279 is a potent and orally active ALK5 inhibitor with an IC50 of 4.7 nM. HM-279 shows cross-reactivity with ALK7 (IC50 = 6.8 nM), but HM-279 has fair to good selectivity against other TGF-β receptor family kinases, with 4.5-693-fold selectivity. HM-279 demonstrates antitumor activity in vivo through CD8+ T cell immunity. HM-279 can be used for the research of colon cancer.
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- CAS No.: 3039954-64-5
- Formule: C22H25N7O2S
- Masse moléculaire:451.54
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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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Help & FAQs
Activité biologique
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ALK5 4.7 nM (IC50) |
ALK7 6.8 nM (IC50) |
ALK1 21.0 nM (IC50) |
ALK2 64.7 nM (IC50) |
BMPR1A 269 nM (IC50) |
ALK4 34.6 nM (IC50) |
ALK6 999 nM (IC50) |
ACVR2A 671 nM (IC50) |
ACVR2B 364 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CT26 | IC50 |
15 μM
Compound: 19f; HM-279
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Antiproliferative activity against mouse CT26 cells
Antiproliferative activity against mouse CT26 cells
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[PMID: 40108955] |
HM-279 exhibits an excellent kinase selectivity and inhibits only 9 kinases: AurA, BUB1/BUB3, FLT4, KDR, NuaK1, PDGFRα, PDGFRβ, QIK, and MST1[1].
HM-279 has very weak antiproliferative activity against CT26 cells (IC50 = 15 μM).
HM-279 (1.5 h; 1-300 nM) strongly inhibits the phosphorylation of Smad3 in A549 cells (IC50 = 21.6 nM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A549 cells
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Concentration:1 nM; 3 nM; 10 nM; 30 nM; 100 nM; 300 nM
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Incubation Time:1.5 h
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Result:Completely inhibited the phosphorylation of Smad3 in 300 nM group.
| Species | Dose | Route | Tmax | Cmax | AUC0-inf | Vss | CL | MRT0-inf | F | T1/2 |
|---|---|---|---|---|---|---|---|---|---|---|
| Dog | 1 mg/kg | i.v. | / | / | / | / | / | / | / | / |
| Dog | 6.72 mg/kg | p.o. | / | / | / | / | / | / | / | / |
| Mice | 30 mg/kg | p.o. | / | / | / | / | / | / | / | / |
| Mice | 5 mg/kg | i.v. | 0.5 h | 9724 ng/mL | 15796 ng·h/mL | 0.21 L/kg | 0.32 L/h/kg | 0.65 h | 44 % | 0.59 h |
| Rat | 1 mg/kg | i.v. | / | / | / | / | / | / | / | / |
| Rat | 10 mg/kg | p.o. | / | / | / | / | / | / | / | / |
HM-279 (30 mg/kg; p.o.; 5days ON/2days OFF; for 15 days) loses its antitumor activity in both female BALB/c Slc-nu/nu mice and female BALB/cCrSlc mice handled with the anti-CD8 antibody (5 mg/kg; i.p.; twice a week), confirming the involvement of CD8+ T cells in the antitumor immune response elicited by HM-279[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/c Slc-nu/nu mice (7 weeks old) were inoculated subcutaneously in the flank with CT26.WT cells (1 × 106 cells) to establish a xenograft model[1].
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Dosage:30 mg/kg
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Administration:p.o.; 5 days ON/2 days OFF; for 15 days
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Result:Did not have antitumor activity.
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Animal Model:Female BALB/cCrSlc mice (7 weeks old) were handled with the anti-CD8 antibody (5 mg/kg; i.p.; twice a week) or isotype control antibody (5 mg/kg; i.p.; twice a week) to establish a CD8-depletion model. Then the mice were inoculated subcutaneously in the flank with CT26.WT cells (1 × 106 cells)[1].
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Dosage:30 mg/kg
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Administration:p.o.; 5 days ON/2 days OFF; for 15 days
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Result:Did not have antitumor activity in the isotype combination group and the anti-CD8 combination group.
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Animal Model:Female BALB/cCrSlc mice (7 weeks old) were inoculated subcutaneously in the flank with CT26.WT cells (1 × 106 cells) to establish a syngeneic model[1].
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Dosage:30 mg/kg; 30 mg/kg plus anti-PD-1 antibody (10 mg/kg; i.p.; BIW)
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Administration:p.o.; 5 days ON/2 days OFF; for 20 days
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Result:Showed partial antitumor activity with TGI of 60% without body weight loss in orally administration.
When used in combination with anti-PD-1 antibody, the TGI was 89%.
Chemical Information
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CAS No. 3039954-64-5
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Masse moléculaire 451.54
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Formule C22H25N7O2S
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SMILES
NC(C1=C(C2=CC(C(N(C)C)=O)=CN2)SC(N(CC3CC3)C4=CN(CC#CC)N=C4)=N1)=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)
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