| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
AZ6102 is a potent and dual inhibitor of tankyrases TNKS1/2 with IC50 values of 3 nM and 1 nM, respectively, it has 100-fold selectivity against other PARP family enzymes and shows 5 nM Wnt pathway inhibition in DLD-1 cells. AZ6102 exhibits good pharmacokinetics in preclinical species, is well-formulated at a clinically relevant intravenous solution concentration of 20 mg/mL, and has low Caco2 efflux to prevent potential tumor resistance mechanisms. The development of embryos, adult tissue homeostasis, and cancer are all significantly impacted by the canonical Wnt pathway. Oncogenesis can result from germline mutations in ß-catenin, Axin, and APC, three elements of the Wnt pathway. Through increased stabilization of Axin, inhibition of the poly(ADP-ribose) polymerase (PARP) catalytic domain of tankyrases (TNKS1 and TNKS2) is known to inhibit the Wnt pathway.
| Targets |
TNKS2 ( IC50 = 2 nM ); TNKS1 ( EC50 = 3 nM ); TNKS1 ( EC50 = 2 μM ); TNKS1 ( EC50 = 0.5 μM )
TNKS1 (enzymatic IC50 = 0.006 μM) [1] - TNKS2 (specific IC50 not provided, but described as a potent dual inhibitor) [1] - PARP1 (enzymatic IC50 > 30 μM) [1] |
|---|---|
| ln Vitro |
AZ6102 inhibits TNKS1 and TNKS2 in enzymatic assays and TCF4 reporter assays (<5nM). AZ6102 has no anti-proliferative effect on the β-catenin mutant cell line HCT-116 or the BRCA mutant cell line MDA-MB-436, but it does inhibit the growth of Colo320DM (GI50 ~40nM). In vitro and in vivo, AZ6102 stabilizes axin2 protein and modifies Wnt target genes in Colo320DM in a dose- and time-dependent manner[1].
AZ6102 exhibited 5 nM Wnt pathway inhibition (IC50 = 0.005 μM) in a DLD-1 cell TCF TOPflash reporter assay [1] - Showed >100-fold selectivity over other PARP family enzymes, with PARP1 IC50 > 30 μM [1] - In a Caco2 permeability assay (pH 7.4), the apparent permeability (AB Papp) was 5.5 × 10⁻⁶ cm/s with an efflux ratio of 2.7, indicating low efflux potential [1] - The compound can be formulated as a clinically relevant intravenous solution at 20 mg/mL [1] |
| ln Vivo |
AZ-6102 (25 mg/kg) is given to naked mice. Its CL is 24 mL/min.kg and its half-life is 4 hours. Upon additional examination in mice and rats, AZ-6102 demonstrates a moderate bioavailability of 12% and 18%, respectively. Analysis of treated DLD-1 cells using Western blot for TNKS1, TNSK2, and Axin2 reveals that, at lower concentrations (at 24, 48, and 72 hours), AZ-6102 stabilized TNSK1, TNSK2, and Axin2 qualitatively stronger and longer than XAV-939. To prevent potential tumor resistance mechanisms, AZ-6102 exhibits good pharmacokinetics in preclinical species with low Caco2 efflux. Moreover, the compound can be prepared at 20 mg/mL in a clinically meaningful intravenous solution at pH 4 with SBECD acting as an excipient. Future research will examine the in vivo effects of TNKS1 and TNSK2 inhibition on tumor xenografts and normal tissue using AZ-6102 as an intravenous probe compound[2].
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| Enzyme Assay |
In pH 7.5 Tris buffer (60 mM Tris, 1 mM DTT, 0.01% (v/v) Tween-20®, 2.5 mM MgCl2, 0.3 mg/mL BSA), 0.11 μM of tankyrase-1 protein and 3 μM nicotinamide adenine dinucleotide (NAD+, 2.12 μM 3H-NAD+ with a specific radioactivity of 1690 Ci/mol, 0.88 μM biotin-NAD+) are used in the assay. A compound (AZ6102) stock solution (10 mM DMSO) is successively diluted two times in DMSO to determine its IC50. Aliquots of the diluted solutions are then placed into 384-well assay plates and combined with Tankyrase-1 solution.
TNKS1 enzymatic inhibition assay: The assay was performed using 110 nM of TNKS1 enzyme to determine the IC50 of compounds. Positive control compounds consistently showed low IC50 values in this system. The assay measures the inhibition of the PARP catalytic domain of tankyrase [1] |
| Cell Assay |
DLD-1 cell Wnt pathway inhibition assay: The TCF TOPflash reporter system was used to evaluate inhibition of Wnt signaling. Cells were treated with various compound concentrations, and IC50 values were calculated based on reporter gene transcriptional activity. For AZ6102, the IC50 was determined to be 5 nM [1]
- Caco2 permeability assay: The apparent permeability (AB Papp) and efflux ratio were assessed at pH 7.4 to predict intestinal absorption and potential efflux transporter-mediated resistance. AZ6102 showed an AB Papp of 5.5 × 10⁻⁶ cm/s and an efflux ratio of 2.7 [1] |
| ADME/Pharmacokinetics |
LogD (pH 7.4): 2.5 [1]
- Aqueous solubility (pH 7.4): 30 μM [1] - Human microsomal intrinsic clearance (CLint): 13 μL/min·mg [1] - Rat hepatocyte intrinsic clearance (CLint): 8 μL/min·10⁶ cells [1] - Caco2 apparent permeability (AB Papp): 5.5 × 10⁻⁶ cm/s, efflux ratio: 2.7 [1] - Rat IV clearance (CL): 11 mL/min·kg [1] - Rat IV steady-state volume of distribution (Vdss): 4.4 L/kg [1] - Rat IV half-life (t1/2): 5.7 hours [1] |
| Toxicity/Toxicokinetics |
Human plasma protein binding (% free): 7.2% (i.e., 92.8% bound) [1]
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| References | |
| Additional Infomation |
AZ6102 is a pyrrolopyrimidinone derivative optimized from a 2-phenylquinazolinone hit compound for in vivo pharmacology hypothesis testing [1]
- It inhibits the Wnt pathway by stabilizing Axin through tankyrase inhibition, leading to β-catenin degradation [1] - High selectivity against PARP1 (IC50 > 30 μM) was achieved to avoid off-target effects [1] - Designed for IV dosing to enable better exposure control and potentially mitigate expected intestinal toxicity [1] |
| Molecular Formula |
C25H28N6O
|
|---|---|
| Molecular Weight |
428.54
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| Exact Mass |
428.232
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| Elemental Analysis |
C, 70.07; H, 6.59; N, 19.61; O, 3.73
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| CAS # |
1645286-75-4
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| Related CAS # |
1645286-75-4
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| PubChem CID |
135905416
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.694
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| LogP |
2.81
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
32
|
| Complexity |
709
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=C1C2C([H])=C([H])N(C([H])([H])[H])C=2N=C(C2C([H])=C([H])C(=C([H])C=2[H])C2=C([H])N=C(C([H])=C2C([H])([H])[H])N2C([H])([H])[C@@]([H])(C([H])([H])[H])N([H])[C@@]([H])(C([H])([H])[H])C2([H])[H])N1[H]
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| InChi Key |
WCPTUQOMNJBIET-CALCHBBNSA-N
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| InChi Code |
InChI=1S/C25H28N6O/c1-15-11-22(31-13-16(2)27-17(3)14-31)26-12-21(15)18-5-7-19(8-6-18)23-28-24-20(25(32)29-23)9-10-30(24)4/h5-12,16-17,27H,13-14H2,1-4H3,(H,28,29,32)/t16-,17+
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| Chemical Name |
2-[4-[6-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-4-methylpyridin-3-yl]phenyl]-7-methyl-3H-pyrrolo[2,3-d]pyrimidin-4-one
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| Synonyms |
AZ6102; AZ-6102; AZ 6102
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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: 25~85 mg/mL (58.3~198.35 mM）
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3335 mL | 11.6675 mL | 23.3350 mL | |
| 5 mM | 0.4667 mL | 2.3335 mL | 4.6670 mL | |
| 10 mM | 0.2334 mL | 1.1668 mL | 2.3335 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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