| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
ALK4 ALK7
AZ12601011 is a potent and selective inhibitor of TGF-beta Receptor 1 (TGFBR1), also known as ALK5. It binds with high affinity (Kd = 2.9 nM) and potently inhibits its kinase activity (IC50 = 18 nM). It also selectively inhibits related kinases ALK4 and ALK7, blocking the phosphorylation of the downstream signaling effector SMAD2. |
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| ln Vitro |
For 20 minutes, AZ12601011 (0.01–10 µM) totally prevents SMAD2 phosphorylation [1]. AZ12601011 (0.01 µM–10 µM) suppresses TGFBR1, ALK4, and ALK7 activities [1]. In vitro, AZ12601011 suppresses the proliferation of 4T1 cells (IC50 = 0.4µM) [1].
In cell-free assays, AZ12601011 potently inhibits TGFBR1 with an IC50 of 18 nM and a Kd of 2.9 nM. By selectively inhibiting ALK4, TGFBR1, and ALK7, it effectively prevents the phosphorylation of SMAD2. This inhibition leads to the suppression of inflammatory cytokine (IL-1beta, IL-6, TNF-alpha) release. |
| ln Vivo |
AZ12601011 (50 mg/kg; twice daily; oral gavage; 25 days) suppresses the growth and spread of tumors in vivo[1].
AZ12601011 is an orally active compound that demonstrates in vivo efficacy by inhibiting mammary tumor growth. By blocking TGFBR1, it suppresses the release of pro-inflammatory cytokines and inhibits tumor progression. It is also being researched for its potential to prevent renal fibrosis. |
| Enzyme Assay |
Cell-free kinase inhibition assays are performed using recombinant TGFBR1 kinase (ALK5). The enzyme is incubated with a biotinylated substrate peptide, ATP, and varying concentrations of AZ12601011. After the reaction, the phosphorylated product is detected using a TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) assay or by measuring ADP formation via a luminescent kinase assay.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: NIH3T3, HaCaT, C2C12, T47D cells Tested Concentrations: 0.01, 0.03, 0.1, 0.3, 1, 3, 10 μM Incubation Duration: 20 minutes Experimental Results: Completely inhibited Phosphorylation of SMAD2. Cellular assays are performed in TGF-beta-responsive cell lines (e.g., Mink Lung Epithelial cells or A549 lung carcinoma cells). Cells are pre-treated with AZ12601011, then stimulated with TGF-beta1 to induce SMAD signaling. The extent of signaling inhibition is measured by Western blot detection of pSMAD2 or by using a SMAD-responsive luciferase reporter system. |
| Animal Protocol |
Animal/Disease Models: Female balb/c (Bagg ALBino) mouse at greater than 18g with tumour[1]
Doses: 50mg/kg Route of Administration: Oral gavage; twice (two times) daily; for 25 days Experimental Results: Inhibited tumor growth and metastasis in vivo. In vivo studies are conducted in mouse models of cancer (e.g., syngeneic 4T1 breast cancer model or MMTV-PyMT transgenic model). AZ12601011 is administered via daily oral gavage. Tumor growth is measured with calipers. At study termination, tumors are collected for analysis of pSMAD2 levels to confirm target engagement and to assess the expression of inflammatory cytokines by qPCR. |
| ADME/Pharmacokinetics |
AZ12601011 is orally bioavailable, enabling convenient dosing in preclinical animal models. Its favorable pharmacokinetic profile allows for sustained inhibition of the TGFBR1 kinase, making it a valuable in vivo tool for studying the effects of blocking the TGF-beta pathway in chronic disease models.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies have shown that AZ12601011 is well-tolerated at effective doses, with no significant acute toxicity reported. However, chronic inhibition of TGF-beta signaling can lead to on-target effects such as severe inflammation and the development of tumors. Caution is advised when designing long-term studies.
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| References | |
| Additional Infomation |
AZ12601011 (molecular formula C19H15N5, MW 313.36) is a highly selective chemical probe for TGFBR1. Its selectivity over other kinases is a key feature, allowing researchers to dissect the specific role of ALK4/5/7-mediated signaling without off-target effects. It is a valuable tool for validating TGF-beta pathway as a therapeutic target in oncology and fibrotic diseases.
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| Molecular Formula |
C19H15N5
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|---|---|
| Molecular Weight |
313.355902910233
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| Exact Mass |
313.132
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| CAS # |
2748337-86-0
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| PubChem CID |
137796280
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
24
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| Complexity |
444
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC2=C(C1)N=C(N=C2N3C=CC4=C3C=CN=C4)C5=CC=CC=N5
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| InChi Key |
KQCNNLRNSIXEJU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H15N5/c1-2-9-21-16(5-1)18-22-15-6-3-4-14(15)19(23-18)24-11-8-13-12-20-10-7-17(13)24/h1-2,5,7-12H,3-4,6H2
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| Chemical Name |
1-(2-pyridin-2-yl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)pyrrolo[3,2-c]pyridine
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 5 mg/mL (15.96 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1912 mL | 15.9561 mL | 31.9122 mL | |
| 5 mM | 0.6382 mL | 3.1912 mL | 6.3824 mL | |
| 10 mM | 0.3191 mL | 1.5956 mL | 3.1912 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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