| Identification | Back Directory | [Name]
IRAK4-IN-3 | [CAS]
2196204-23-4 | [Synonyms]
AZ1495
IRAK4-IN-3
7H-Pyrrolo[2,3-d]pyrimidin-4-amine, N-[trans-4-(4-morpholinyl)cyclohexyl]-5-(tetrahydro-2H-pyran-4-yl)- | [Molecular Formula]
C21H31N5O2 | [MDL Number]
MFCD31813626 | [MOL File]
2196204-23-4.mol | [Molecular Weight]
385.5 |
| Chemical Properties | Back Directory | [density ]
1.265±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 10 mg/mL (25.94 mM) | [form ]
Solid | [pka]
13.07±0.50(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
AZ1495, a weak base, is a potent orally active interleukin-1 receptor associated kinase 4 (IRAK4) inhibitor. AZ1495 has a favorable physicochemical and kinase selectivity for IRAK4 and IRAK1 with IC50 values of 0.005 μM and 0.023 μM, respectively. AZ1495 has IRAK4 inhibition with a Kd value of 0.0007 μM. AZ1495 can be used for the research of diffuse large B-cell lymphoma (DLBCL)[1]. | [in vivo]
AZ1495 (compound 28) (oral, daily, 12.5 mg/kg) leds to tumor regression combination with ibrutinib in an ABC-DLBCL mouse model (OCI-LY10 cells)[1].
AZ1495 (iv., 2 mg/kg and oral, 5mg/kg) is characterized by high clearance (Cl) in rat (75 mL/min/kg) and moderate predictions based on hepatocyte data (Clint 15 μl/min/106 cells, predicted clearance 42 mL/min/kg) with low bioavailability consistent with a high first pass effect[1].
AZ1495 (iv., 1 mg/kg) has low the amount of active renal secretion occurring in the dog[1]. | Animal Model: | CB.17 SCID mice[1] | | Dosage: | 12.5 mg/kg | | Administration: | oral, daily, 12.5 mg/kg | | Result: | Had modest anti-tumor activity as single agents but a combination ofibrutinib led to tumor regression and is well tolerated. |
| Animal Model: | rat[1] | | Dosage: | 2 mg/kg, 5mg/kg | | Administration: | iv., 2 mg/kg and oral, 5mg/kg | | Result: | | Species | Dose (mg/kg) | Cl (mL/min/kg) | Vss(L/kg) | PO halflife (h) | IV halflife (h) | Fabs (%) | F (%) | | Rat | 2，5 | 75 | 2.1 | 2.0 | 0.8 | 100 | 28 | | Dog | 1 | 29 | 3.0 | - | 3.3 | - | - | |
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| Animal Model: | dog[1] | | Dosage: | 1 mg/kg | | Administration: | iv., 1 mg/kg | | Result: | | Species | Dose (mg/kg) | Cl (mL/min/kg) | Vss(L/kg) | PO halflife (h) | IV halflife (h) | Fabs (%) | F (%) | | Rat | 2，5 | 75 | 2.1 | 2.0 | 0.8 | 100 | 28 | | Dog | 1 | 29 | 3.0 | - | 3.3 | - | - | |
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| [IC 50]
IRAK4: 5 nM (IC50); IRAK1: 23 nM (IC50); CLK1: 50 nM (IC50); CLK2: 5 nM (IC50); CLK4: 8 nM (IC50); haspin: 4 nM (IC50) | [References]
[1] Scott JS, et al. Discovery and Optimization of Pyrrolopyrimidine Inhibitors of Interleukin-1 Receptor Associated Kinase 4 (IRAK4) for the Treatment of Mutant MYD88L265P Diffuse Large B-Cell Lymphoma. J Med Chem. 2017 Dec 28;60(24):10071-10091. DOI:10.1021/acs.jmedchem.7b01290 |
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| Company Name: |
cjbscvictory
|
| Tel: |
13348960310 |
| Website: |
https://www.weikeqi-biotech.com/ |
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