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.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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- Pureté et documentation
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Help & FAQs
Activité biologique
Description
IC50 & Target
[1]|
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) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| 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] |
In Vitro
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. Further protocols information, click here.
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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.
Parmacokinetics
| 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. | / | / | / | / | / | / | / | / |
In Vivo
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.
Protocole
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Research Protocol for Cancer Immunology
Cancer immunology studies how the immune system recognizes, suppresses, edits, or fails to eliminate malignant cells through tumor antigen release, antigen presentation, T-cell priming, immune trafficking, tumor-cell killing, and feedback inhibition in the tumor microenvironment. The cancer-immunity cycle links tumor antigenicity, dendritic-cell priming, CD8+ T-cell infiltration, cytotoxic function, and immune-checkpoint regulation to tumor rejection or immune escape. Immune-checkpoint pathways such as PD-1/PD-L1 and CTLA-4 suppress antitumor T-cell activity and can be therapeutically blocked, but many tumors remain resistant because of poor antigen presentation, weak T-cell infiltration, suppressive myeloid cells, regulatory T cells, and tumor-intrinsic immune-exclusion programs. Unresolved questions include which immune-cell states predict response, how tumor-intrinsic pathways exclude immune cells, how myeloid suppression limits checkpoint blockade, and which combination strategies
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
HM-279 Related Classifications
HY-185430 Related Classifications
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