HYL001
Based on 1 Customer Validation
HYL001 is an orally active, selective ALK4/ALK5 inhibitor with Kd values of 13 nM and 22.5 nM for ALK4 and ALK5, respectively. HYL001 inhibits GLS expression. HYL001 impairs glutamine metabolism, mitochondrial respiration, the TCA cycle, oxidative phosphorylation, ATP production, and redox balance, while selectively targeting mitochondria, disrupting mitochondrial structure, and inducing Apoptosis and ROS. HYL001 inhibits tumor growth and liver metastasis. HYL001 can be used in research on breast cancer, hepatocellular carcinoma, and microsatellite-stable colorectal cancer metastasis.
For research use only. We do not sell to patients.
- Purity : 99.94%
- CAS No.: 2426547-83-1
- Formula: C21H18N4O
- Molecular Weight:342.39
-
Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Protocols
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
Description
IC50 & Target
TGFβ[1]
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| H22 | IC50 |
1.4 μM
|
Cytotoxicity against murine H22 hepatocellular carcinoma cells with IC50 1.4 µM.
Cytotoxicity against murine H22 hepatocellular carcinoma cells with IC50 1.4 µM.
|
36958408 |
| HEK-293T | IC50 |
72 nM
|
Inhibition of TGFβ pathway activity in HEK293T cells transfected with 12xCAGA-Firefly_Luc and Tk-Renilla_Luc reporters incubated 16 hrs with 5 ng/mL TGFB1 measured by dual luciferase assay.
Inhibition of TGFβ pathway activity in HEK293T cells transfected with 12xCAGA-Firefly_Luc and Tk-Renilla_Luc reporters incubated 16 hrs with 5 ng/mL TGFB1 measured by dual luciferase assay.
|
39816803 |
In Vitro
HYL001 exhibits marginal inhibitory activity against purified recombinant GLS[2].
HYL001 (1-10 µM) inhibited 4T1 TRC colony formation, with 100% inhibition at 10 µM, and inhibited preformed 4T1 TRC colonies by 60% at 10 µM[2].
HYL001 (1-10 µM) inhibits HCSC with an IC50 340-fold lower than that of LND, and inhibits H22 TRC colony growth at 1 µM, with an inhibition rate of 58% at 10 µM[2].
HYL001 inhibits breast CSC and HCC stem cells, with IC50 values 380-fold and 340-fold lower than Lonidamine (HY-B0486), respectively[4].
HYL001 (0.1-10,000 nM; 16 hours) inhibits TGFβ pathway activity in HEK293T reporter cells with an IC50 of 72 nM[5].
HYL001 is a potent inhibitor of ALK4 and ALK5, with Kd values of 13 nM and 22.5 nM, respectively, in cell-free competitive binding assays[7].
HYL001 inhibited ALK5 with an IC50 of 177 nM and p38α with an IC50 of 548 nM in recombinant kinase activity assays[7].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:BCSCs
-
Concentration:1, 3, 5 µM
-
Incubation Time:12 h
-
Result:The apoptosis rate of BCSCs was 30%, 32%, and 55% after HYL001 exposure at 1 µM, 3 µM, and 5 µM for 12 h, respectively.
Parmacokinetics
| Species | Dose | Route | Tmax | Cmax | AUClast | AUCinf | T1/2 | CL/F |
|---|---|---|---|---|---|---|---|---|
| Mice[5] | 71 mg/kg | p.o. | 0.25 h | 2050 ng/mL | 3520 ng·h/mL | 4110 ng·h/mL | 2.45 h | 288 mL/min/kg |
In Vivo
HYL001 (5 μmol/kg; s.c.; once every three days; five injections) suppresses lung metastasis and prolongs survival in the metastatic 4T1 tumor model in BALB/c mice[2].
HYL001 (10 μmol/kg; i.v.; every 2 days; 5 doses) inhibits orthotopic 4T1 tumor growth in female BALB/c mice, with ~28% tumor inhibition by weight, ~57% reduction in intratumoral Glu/Gln ratio, reduced GLS expression, and decreased CD133 CSC staining[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:BALB/c (female, five-week-old)[2]
-
Dosage:5 μmol/kg
-
Administration:s.c.; once every three days; five injections
-
Result:Inhibited tumor growth with a tumor inhibition rate (TIR) of 44% in tumor volume.
Reduced the proportion of CD133+ cancer cells by 82.1%, side population cells by 62.1%, and CD44+CD24− cancer cells by 38.2% relative to saline.
The G0/G1 ratio of CD133+ cancer cells declined from 90% to 70%.
Enhanced ROS and reduced GSH in subcutaneous 4T1 tumor tissues.
-
Animal Model:BALB/c (female, five-week-old)[2]
-
Dosage:5 μmol/kg
-
Administration:s.c.; once every three days; five injections
-
Result:Reduced pulmonary metastatic nodules from nearly 300 in the saline group to 60.
Overall survival was prolonged by 10 days (31.2%) over the saline group.
Circulating tumor cells and circulating tumor stem cells were significantly lower in mice given HYL001 than in saline or LND groups.
Greater reduction was noted in circulating tumor stem cells than in circulating tumor cells after HYL001 administration.
Lung wet weight was mildest in the HYL001 group.
-
Animal Model:BALB/c (female, five-week-old)[2]
-
Dosage:10 μmol/kg (monotherapy); 10 μmol/kg plus PTX 20 μmol/kg
-
Administration:i.v.; once every three days; five times
-
Result:Monotherapy achieved a tumor inhibition rate (TIR) of 36%.
HYL001 plus PTX achieved a TIR of 75%.
Relative Glu/Gln values were reduced to 49% after HYL001 administration and to 31% after HYL001 plus PTX administration relative to saline.
Decreased GSH and enhanced mitochondrial ROS in orthotopic 4T1 tumor tissues.
Significantly reduced CD133+ cells, with green fluorescence intensity declining by around 90%.
CSC populations including CD133+ cells, CD44+CD24− cells, and side population cells were decreased in tumors from mice given HYL001.
-
Animal Model:BALB/c (female, SPF, 16-20 g)[6]
-
Dosage:10 μmol/kg
-
Administration:i.v.; once every 2 days; 5 doses
-
Result:Tumor inhibition rate by weight was ~28% in the HYL001 group.
Intratumoral Glu/Gln ratio was reduced by ~57% in the free HYL001 group compared with Saline.
GLS expression was drastically reduced in orthotopic 4T1 tumor tissues upon administration of free HYL001.
CD133 fluorescence staining confirmed that HYL001 administration declined CSCs in orthotopic 4T1 tumor tissues.
- RNA extraction experimental
- Western Blot
- Annexin V plus membrane-impermeant dye apoptosis staining
- ROS/oxidative-stress fluorescent staining
- Patient-Derived Orthotopic Xenograft (PDOX)
- Liver Cancer Modeling
- Breast Cancer Modeling
- Kinase activity and phosphorylation assays
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Patient-Derived Xenograft (PDX)
- Apoptosis Solutions
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Protocol for Kinase activity and phosphorylation assays
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
Chemical Information
-
CAS No. 2426547-83-1
-
Appearance Solid
-
Molecular Weight 342.39
-
Formula C21H18N4O
-
Color White to off-white
-
SMILES
OC1=CC2=C(C3=C(CCC4)N4N=C3C5=CC=CC(C)=N5)C=CN=C2C=C1
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 17.5 mg/mL (51.11 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
-
Data Sheet (301 KB)
-
SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
-
Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.9206 mL | 14.6032 mL | 29.2065 mL | 73.0161 mL |
| 5 mM | 0.5841 mL | 2.9206 mL | 5.8413 mL | 14.6032 mL | |
| 10 mM | 0.2921 mL | 1.4603 mL | 2.9206 mL | 7.3016 mL | |
| 15 mM | 0.1947 mL | 0.9735 mL | 1.9471 mL | 4.8677 mL | |
| 20 mM | 0.1460 mL | 0.7302 mL | 1.4603 mL | 3.6508 mL | |
| 25 mM | 0.1168 mL | 0.5841 mL | 1.1683 mL | 2.9206 mL | |
| 30 mM | 0.0974 mL | 0.4868 mL | 0.9735 mL | 2.4339 mL | |
| 40 mM | 0.0730 mL | 0.3651 mL | 0.7302 mL | 1.8254 mL | |
| 50 mM | 0.0584 mL | 0.2921 mL | 0.5841 mL | 1.4603 mL |
HYL001 Related Classifications
HY-160237 Related Classifications
Powered by Bioz