Welcome to LookChem.com Sign In|Join Free

CAS

  • or

1110813-31-4

Post Buying Request

1110813-31-4 Suppliers

Recommended suppliersmore

  • Product
  • FOB Price
  • Min.Order
  • Supply Ability
  • Supplier
  • Contact Supplier

1110813-31-4 Usage

Description

Different sources of media describe the Description of 1110813-31-4 differently. You can refer to the following data:
1. Dacomitinib is a selective and irreversible inhibitor of EGFR. It is a drug candidate for the treatment of non-small cell lung carcinoma. It is current under the Phase III clinical trials. It also shows potential for the treatment of HER-2 amplified breast cancer cells lines that are resistant to trastuzumab and lapatinib.
2. The epidermal growth factor receptors (EGFR), whose members include ErbB1 (HER1), ErbB2 (HER2), ErbB3 (HER3), and ErbB4 (HER4), are receptor tyrosine kinases that are often over-expressed in cancer. PF-299804 is a second generation pan-ErbB receptor tyrosine kinase inhibitor (IC50s = 6, 45.7, and 73.7 nM for ErbB1, ErbB2, and ErbB4, respectively) that irreversibly binds to the ATP site in the catalytic domains of ErbB receptors. At 15 mg/kg, it demonstrates antitumor activity ranging from delay in tumor growth to complete regression in various tumor xenograft models expressing either wild-type ErbB or mutant ErbB family members that show resistance to first generation ErbB kinase inhibitors.

Biological activity

Dacomitibib (Dacomitinib, PF299804) is an effective and irreversible pan-ErbB inhibitor that is most effective in EGFR, with an IC50 of 6 nM. It is also highly effective in NSCLCs that carries EGFR or ERBB2 mutants (against Gefitinib) and EGFR T790M mutant. Phase 2. Dacomitinib is taken orally once-daily. It is an irreversible inhibitor of HER-1 (EGFR), HER-2 and HER-4 tyrosine kinases. Dacomitinib targets multiple receptors of the HER pathway, whereas currently marketed HER-1 (EGFR) inhibitors for non-small cell lung cancer (NSCLC) target only one receptor in this pathway,developed by Pfizer.

Uses

Different sources of media describe the Uses of 1110813-31-4 differently. You can refer to the following data:
1. Dacomitinib (PF299804), which name is (E)-N-[4-(3-chloro-4-fluoroanilino)-7- methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide, is a potent, orally available, highly selective, irreversible small-molecule tyrosine kinase inhibitor (TKI) of tyrosine kinase human epidermal growth factor receptors (HER) 1 (EGFR), HER2, and HER4. It is most effective against EGFR with IC50 of 6 nM. It is highly effective against NSCLCs carrying EGFR or ERBB2 mutant (anti-Gefitinib) and EGFR T790M mutant.
2. Dacomitinib is an Erb-inhibitor, or an inhibitor of the members of the epidermal growth factor receptor family. Used as an ant-cancer agent due to observation of over-expressed epidermal growth factor receptor in nearly all cases of squamous cell carcinoma in the head and neck.

Clinical Study

Dacomitinib has advanced to several Phase III clinical trials. The results of the first trials were disappointing, with a failure to meet the study goals, Additional Phase III trials are ongoing. Clinical evaluation of dacomitinib is ongoing in a number of clinical trials in patients with advanced NSCLC across lines of therapies and a range of histologies and molecular subtypes, such as EGFR and KRAS status. Additionally, there is an ongoing clinical trial evaluating dacomitinib in recurrent and/or metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN).

Definition

ChEBI: A member of the class of quinazolines that is 7-methoxyquinazoline-4,6-diamine in which the amino group at position 4 is substituted by a 3-chloro-4-fluorophenyl group and the amino group at position 6 is substituted by an (E)-4-(piperidin 1-yl)but-2-enoyl group.

in vitro

dacomitinib reduced the phosphorylation of her2, egfr, her4, akt, anderkin the majority of sensitive lines. dacomitinib exerted its antiproliferative effect through a combined g0–g1 arrest and an induction of apoptosis. dacomitinib inhibited growth in several her2-amplified lines with de novo and acquired resistance to trastuzumab. dacomitinib maintained a high activity in lines with acquired resistance to lapatinib. this study identifies her2-amplified breast cancer lines as most sensitive to the antiproliferative effect of dacomitinib and provides a strong rationale for its clinical testing in her2-amplified breast cancers resistant to trastuzumab and lapatinib [1].

in vivo

to evaluate the in vivo efficacy of pf00299804, the authors generated xenografts in nu/nu mice using hcc827 gfp and hcc827 del/t790m cells and treated the mice with pf00299804. pf00299804 effectively inhibited the growth of hcc827 gfp xenografts. pf00299804 treatment was substantially more effective at inhibiting growth of this xenograft model than gefinitib. thus, these preclinical models suggest that pf00299804 may be quite effective against lung cancers that become resistant to gefitinib or erlotinib via acquisition of a t790m mutation in egfr [2].

IC 50

6 nm (egfr); 45.7 nm (erbb2); 73.7 nm (erbb4)

references

[1] kalous o, conklin d, desai aj, o'brien na, ginther c, anderson l, cohen dj, britten cd, taylor i, christensen jg, slamon dj, finn rs. dacomitinib (pf-00299804), an irreversible pan-her inhibitor, inhibits proliferation of her2-amplified breast cancer cell lines resistant to trastuzumab and lapatinib. mol cancer ther. 2012;11(9):1978-87.[2] engelman ja, zejnullahu k, gale cm, lifshits e, gonzales aj, shimamura t, zhao f, vincent pw, naumov gn, bradner je, althaus iw, gandhi l, shapiro gi, nelson jm, heymach jv, meyerson m, wong kk, jfinne pa. pf00299804, an irreversible pan-erbb inhibitor, is effective in lung cancer models with egfr and erbb2 mutations that are resistant to gefitinib. cancer res. 2007;67(24):11924-32.

Check Digit Verification of cas no

The CAS Registry Mumber 1110813-31-4 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,1,1,0,8,1 and 3 respectively; the second part has 2 digits, 3 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 1110813-31:
(9*1)+(8*1)+(7*1)+(6*0)+(5*8)+(4*1)+(3*3)+(2*3)+(1*1)=84
84 % 10 = 4
So 1110813-31-4 is a valid CAS Registry Number.
InChI:InChI=1S/C24H25ClFN5O2/c1-33-22-14-20-17(24(28-15-27-20)29-16-7-8-19(26)18(25)12-16)13-21(22)30-23(32)6-5-11-31-9-3-2-4-10-31/h5-8,12-15H,2-4,9-11H2,1H3,(H,30,32)(H,27,28,29)/b6-5+

1110813-31-4SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 17, 2017

Revision Date: Aug 17, 2017

1.Identification

1.1 GHS Product identifier

Product name Dacomitinib

1.2 Other means of identification

Product number -
Other names Dacomitinib [USAN]

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:1110813-31-4 SDS

1110813-31-4Downstream Products

1110813-31-4Relevant articles and documents

Preparation method of dacomitinib intermediate

-

, (2021/04/28)

The invention provides a preparation method of a dacomitinib intermediate. The preparation method comprises steps shown in the specification. The invention provides the novel preparation method of the dacomitinib key intermediate, the intermediate is short in synthetic route, mild in reaction condition, short in reaction time and simple in separation and purification method, raw materials and reagents are conventional reagents, the cost is low, the yield of the prepared product is high, and the method is very beneficial to industrial production and popularization and has a good application prospect.

Preparation method of dacotinib

-

, (2022/01/10)

The present invention discloses a method of preparation of dacotinib, comprising the following steps: (N- (3-chloro-4-fluorophenyl) -7-fluoro-6-nitro-4-quinazoline) in a base / methanol system to undergo a methyl oxidation reaction, to compound 02 (N- (3-

Preparation method of dacrotinib

-

, (2021/07/01)

The invention provides a preparation method of dacrotinib. Specifically, methyl 3-amino-4-methylbenzoate used as a raw material is subjected to condensation, nitration, reduction, ring closing, halogenation and coupling to obtain the dacotinib. The preparation method provided by the invention has the advantages of cheap and easily available raw materials, simple reaction and post-treatment operation and high yield, and is suitable for industrial production.

Post a RFQ

Enter 15 to 2000 letters.Word count: 0 letters

Attach files(File Format: Jpeg, Jpg, Gif, Png, PDF, PPT, Zip, Rar,Word or Excel Maximum File Size: 3MB)

1

What can I do for you?
Get Best Price

Get Best Price for 1110813-31-4