1224844-38-5

Basic information

• Product Name: 5-(4-aMino-1-isopropyl-1H-pyrazolo[3,4-d]pyriMidin-3-yl)benzo[d]oxazol-2-aMine
• Synonyms: 5-(4-aMino-1-isopropyl-1H-pyrazolo[3,4-d]pyriMidin-3-yl)benzo[d]oxazol-2-aMine;3-(2-Amino-5-benzoxazolyl)-1-(1-methylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;INK-128;-(4-aMino-1-isopropyl-1H-pyrazolo[3,4-d]pyriMidin-3-yl)benzo[d]oxazol-2-aMine;INK 128 (MLN0128);3-(2-aminobenzo[d]oxazol-5-yl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine;INK-128 3-(2-Amino-5-benzoxazolyl)-1-(1-methylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;MLN0128
• CAS NO: 1224844-38-5
• Molecular Formula: C15H15N7O
• Molecular Weight: 309.3259
• Product Categories: PI3K/Akt/mTOR;Inhibitors;Akt;mTOR;PI3K
• Mol File: 1224844-38-5.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 598.8±60.0 °C(Predicted)
• Appearance: /
• Density: 1.64
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to 25 mg/ml)
• PKA: 3.77±0.30(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: 5-(4-aMino-1-isopropyl-1H-pyrazolo[3,4-d]pyriMidin-3-yl)benzo[d]oxazol-2-aMine(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(4-aMino-1-isopropyl-1H-pyrazolo[3,4-d]pyriMidin-3-yl)benzo[d]oxazol-2-aMine(1224844-38-5)
• EPA Substance Registry System: 5-(4-aMino-1-isopropyl-1H-pyrazolo[3,4-d]pyriMidin-3-yl)benzo[d]oxazol-2-aMine(1224844-38-5)

Safety Data

• Hazardous Substances Data: 1224844-38-5(Hazardous Substances Data)

Usage

Description

5-(4-aMino-1-isopropyl-1H-pyrazolo[3,4-d]pyriMidin-3-yl)benzo[d]oxazol-2-aMine, also known as INK128, is a potent and selective TORC1/2 inhibitor with broad oral antitumor activity. It is an ATP-dependent inhibitor of mTOR kinase, characterized by its ability to block the phosphorylation of downstream substrates of both TORC1 and TORC2. INK128 is distinct from rapamycin and offers a novel approach to cancer treatment by targeting translational control, cell metabolism, growth, and angiogenesis.

Uses

Used in Anticancer Applications:
5-(4-aMino-1-isopropyl-1H-pyrazolo[3,4-d]pyriMidin-3-yl)benzo[d]oxazol-2-aMine is used as an anticancer agent for its potent and selective inhibition of TORC1/2. It is effective against various types of cancer, including those resistant to rapamycin and pan-PI3K inhibitors. The compound demonstrates its efficacy through oral administration, which inhibits angiogenesis and tumor growth in several xenograft models. Additionally, INK128's impact on gene expression contributes to the reduction of invasion and metastasis in cancer cells.
Used in Pharmaceutical Research:
In the pharmaceutical industry, 5-(4-aMino-1-isopropyl-1H-pyrazolo[3,4-d]pyriMidin-3-yl)benzo[d]oxazol-2-aMine is used as a research compound for the development of new cancer treatments. Its unique mechanism of action and effectiveness against resistant cancer cells make it a valuable asset in the search for innovative therapeutic strategies.
Used in Drug Delivery Systems:
Similar to gallotannin, 5-(4-aMino-1-isopropyl-1H-pyrazolo[3,4-d]pyriMidin-3-yl)benzo[d]oxazol-2-aMine may also benefit from novel drug delivery systems to enhance its applications and efficacy against cancer cells. The development of organic and metallic nanoparticles as carriers for INK128 delivery could potentially improve its bioavailability and therapeutic outcomes, making it a more effective treatment option for various types of cancer.

Biological Activity

Sapanisertib (MLN0128, INK 128, TAK-228) is a potent and selective mTOR inhibitor with IC50 of 1 nM in cell-free assays; >200-fold less potent to class I PI3K isoforms, superior in blocking mTORC1/2 and sensitive to pro-invasion genes (vs Rapamycin). Phase 1.

in vitro

INK 128 exhibits an enzymatic inhibition activity against mTOR and more than 100-fold selectivity to PI3K kinases. As TORC1/2 inhibitor, INK 128 inhibits both the phosphorylation of S6 and 4EBP1, the downstream substrates of TORC1, and selectively inhibits AKT phosphorylation at Ser473, the downstream substrate of TORC2. Furthermore, INK 128 also shows potent inhibition effects on cell lines resistant to rapamycin and pan-PI3K inhibitors.

in vivo

In a ZR-75-1 breast cancer xenograft model, INK 128 shows tumor growth inhibition efficacy at a dose of 0.3 mg/kg/day. Daily, oral administration of INK 128 inhibits angiogenesis and tumor growth in multiplexenograft models.

References

1) Hsieh?et al.?(2012),?The translational landscape of mTOR signaling steers cancer initiation and metastasis; Nature,?485?55 2) Gokmen-Polar?et al.?(2012)?Investigational drug MLN0128, a novel TORC1/2 inhibitor, demonstrates potent oral antitumor activity in human breast cancer xenograft models; Breast Cancer Res. Treat.,?136?673

Upstream product

• 1404480-15-4 2-amino-benzooxazole-5-boronic acid hydrochloride 
• 83255-86-1 3-bromo-4-aminopyrazolo<3,4-d>pyrimidine 
• 1224844-66-9 5-( 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]oxazol-2-amine 
• 40925-68-6 2-amino-4-bromo-phenol 
• 64037-07-6 5-bromo-1,3-benzoxazol-2-amine 
• 89-41-8 4-methoxy-3-nitrobenzoic acid 
• 10397-28-1 4-methoxy-3-nitrobenzoyl chloride 
• 506-68-3 bromocyane 
• 2380-63-4 4-Aminopyrazolo<3,4-d>pyrimidin 

Relevant articles and documents

Synthesis process of anti-tumor drug Sapanisertib

The invention discloses a synthesis process of anti-tumor drug Sapanisertib. The synthesis process comprises the following steps: step 1, carrying out carboxyl halogenation reaction on a compound I and a halogenating reagent in a proper solvent to obtain

KINASE INHIBITOR POLYMORPHS

Polymorphs, hydrates, and solvates of chemical compounds that modulate kinase activity, including mTOR activity, and chemical compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including mTOR activity, are described herein.