Oritinib - ≥99% , CAS No.2035089-28-0

CAS: 2035089-28-0 Cat. No.: O648111 Formula: C₃₁H₃₇N₇O₂ Peso molecolare: 539.67

GRADE & PURITY ≥99%

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Panoramica

Oritinib (SH-1028), an irreversible third-generation EGFR TKI , overcomes T790M-mediated resistance in non-small cell lung cancer . Oritinib (SH-1028), a mutant-selective inhibitor of EGFR kinase activity, inhibits EGFR WT , EGFR L858R , EGFR L861Q , EGFR L858R/T790M , EGFR d746-750 and EGFR d746-750/T790M kinases, with IC 50 s of 18, 0.7, 4, 0.1, 1.4 and 0.89 nM, respectively

In Vitro

Oritinib (SH-1028) binds irreversibly to EGFR kinase by targeting cysteine-797 residue in the ATP binding site via covalent bond formation. Oritinib (0.001-10 μM) potently and selectively targets mutant EGFR cell lines in vitro. Oritinib (0.1 μM) continuously inhibits the phosphorylation of EGFR in PC-9 and NCI-H1975 cells at lower concentrations or even drug-free for at least 6 h. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell Line: A431 (EGFR WT ), H3255 (EGFR L858R ), PC-9 (EGFR d746-750 ) and NCI-H1975 (EGFR L858R/T790M ) cells Concentration: 0.001, 0.01, 0.1, 1, and 10 μM Incubation Time: 72 hours Result: Selectively inhibited EGFR-mutated NCI-H1975, H3255 and PC-9 cells, with IC 50 s of 3.93±1.12, 9.39±0.88 and 7.63±0.18 nmol/L, respectively, which were about 198-, 83- and 102-fold more sensitive than the inhibition of wild-type EGFR in A431 cells (IC 50 =778.89±134.74 nM).

In Vivo

Oral administration of Oritinib at a daily dose of 5 mg/kg significantly inhibits proliferation of tumor cells with EGFR sensitive mutation (exon 19 del) and resistant mutation (T790 M) for consecutive 14 days, with no TKI-induced weight loss in mouse xenograft models . Oritinib shows good bioavailability, and is distributed extensively from the plasma to the tissues . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: 6-8 weeks old female mice bearing NCI-H1975 and A431 xenograft models Dosage: 2.5, 5, and 15 mg/kg Administration: Orally administrated once daily for consecutive 14 days Result: Led to a significant inhibition of tumor cell growth in both PC-9 (exon 19 del) and NCI-H1975 (L858R/T790M) xenograft models. Animal Model: NCI-H1975 tumor-bearing mice Dosage: 2.5, 5, and 15 mg/kg (Pharmacokinetic Analysis) Administration: Oral administration for 1 day or 14 consecutive days. Result: The T max is 1.5-2 h, indicating rapidly distributed into tissues, including lung tumor tissues. The AUC 0–t values in plasma were 118, 300 and 931 ng×h/mL on Day 1, while 272, 308 and 993 ng×h/ml on Day 14, respectively.

Form:Solid

IC50& Target:EGFR (WT) 18 nM (IC 50 ) EGFR L858R 0.7 nM (IC 50 ) EGFR L861Q 4 nM (IC 50 ) EGFR L858R/T790M 0.1 nM (IC 50 ) EGFR d746-750 1.4 nM (IC 50 ) EGFR d746-750/T790M 0.89 nM (IC 50 )

Specifications

Specifiche e purezza

≥99%

Meccanismi biochimici e fisiologici

Oritinib (SH-1028), an irreversible third-generation EGFR TKI , overcomes T790M-mediated resistance in non-small cell lung cancer . Oritinib (SH-1028), a mutant-selective inhibitor of EGFR kinase activity, inhibits EGFR WT , EGFR L858R , EGFR L861Q , EGFR

Condizioni di conservazione di stoccaggio

Store at -20°C

Spedito in

Ice chest + Ice pads

Questo prodotto richiede spedizione a catena fredda. I servizi di terra e altri servizi economici non sono disponibili.

Tipo di azione

INHIBITOR

Purezza

≥99%

Nomi e identificatori

• Peso molecolare: 539.67

Proprietà chimiche e fisiche

• Solubilità: DMSO : 125 mg/mL (231.62 mM; Need ultrasonic)

Domande frequenti

What is the purity of this product?

This product is supplied at ≥99% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at ?20 °C. Freezer storage is required to maintain the specified shelf life.

How is this product shipped?

This product ships in an insulated container with ice pads. Unpack on arrival and transfer it to the storage condition stated above.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 2035089-28-0, the molecular formula is C31H37N7O2, and the molecular weight is 539.67 g/mol.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.